Paternal factors and low birthweight, preterm, and small for gestational age births: a systematic review

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Paternal factors and low birthweight, preterm, and small for gestational age births: a systematic review Prakesh S. Shah; on behalf of the Knowledge Synthesis Group on determinants of preterm/low birthweight births

L

ow birthweight (LBW) birth and preterm births (PTBs) are public health issues with significant individual, familial, and societal impact. Familial influence in the cause of LBW/PTB births is suspected; however, the major research attention has been focused on maternal determinants. Paternal factors (such as advanced paternal age1 and chemical exposures) have been linked with congenital malformations. De La Rochebrochard et al,2 in a minireview, concluded that advanced paternal age (⬎40 years) was associated with miscarriages and fetal deaths. Diseases such as Alpert syndrome, Marfan syndrome, and Waardenberg syndrome are associated with advanced paternal age. Strobino et al3 reviewed the connection between paternal occupational exposure and effect on offspring. They reported that paternal occupation was not associFrom the Department of Pediatrics, Mount Sinai Hospital, and the Departments of Pediatrics and of Health Policy, Management and Evaluations, University of Toronto, Toronto, Ontario, Canada. Received May 24, 2009; revised July 31, 2009; accepted Aug. 19, 2009. Reprints: Prakesh S. Shah, MD, Department of Paediatrics, Mount Sinai Hospital, 775A-600 University Ave., Toronto, Ontario, Canada M5G 1X5. [email protected]. This study was supported by funding from the Canadian Institute of Health Research (CIHR) Knowledge Synthesis/Translation Grant no. KRS 86242. The CIHR has played no role in the analyses, the writing of the report, the interpretation of data, or the decision to submit the manuscript. 0002-9378/free © 2010 Published by Mosby, Inc. doi: 10.1016/j.ajog.2009.08.026

For Editors’ Commentary, see Table of Contents See related editorial, page 99

A systematic review of the risks of a low birthweight (LBW), preterm, and small-forgestational-age births in relation to paternal factors was performed. Medline, Embase, Cumulative Index of Nursing and Allied Health Literature, and bibliographies of identified articles were searched for English-language studies. Study qualities were assessed according to a predefined checklist. Thirty-six studies of low-to-moderate risk of bias were reviewed for various paternal factors: age, height, weight, birthweight, occupation, education, and alcohol use. Extreme paternal age was associated with higher risk for LBW. Among infants who were born to tall fathers, birthweight was approximately 125-150 g higher compared with infants who were born to short fathers. Paternal LBW was associated with lower birthweight of the offspring. In conclusion, paternal characteristics including age, height, and birthweight are associated with LBW. Paternal occupational exposure and low levels of education may be associated with LBW; however, further studies are needed. Key words: anthropometry, intergenerational effects, paternal age, paternal birthweight, paternal occupation

ated with spontaneous abortion and that there was a lack of conclusive impact on other birth outcomes. Studies have reported paternal factors that influence birthweight or gestational age. However, no comprehensive review of paternal determinants or factors on LBW, PTB, or small for gestational age (SGA) births has been conducted. The objective of this study was to review systematically the risk of an infant with LBW, PTB, and SGA in relation to various reported paternal factors.

M ATERIALS AND M ETHODS The data were extracted from published articles; therefore, no ethical approval was obtained.

Criteria for consideration of studies for this review Observational studies that explored the association of any of the paternal factors and the outcomes of LBW, PTB, and SGA births of offspring were included in this review. If the study provided adequate information on the method of ascertainment of the paternal factor and its

effects on any of the outcomes of interest, the study was eligible for inclusion in the review. We included only information that was available from the publications and did not contact primary authors. Studies that were published as abstracts were excluded.

Types of studies Observational cohort studies, case control studies, and studies of surveys or interviews were included. Reports of data from national or local vital statistics that were not published as peer-reviewed articles were not included. Types of participants Women who had a live birth were included. Data on reports of maternal influence on birth outcomes were not included in this review. Assessment of exposure Previous knowledge of the subject indicated that paternal age, anthropometry, paternal birthweight, occupation, and educational background would be probable exposures to be included in the review.4 We did not include paternal race as an exposure variable because race has

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a complex interaction with maternal race. Similarly, we excluded paternal smoking as an exposure because most studies have reported on environmental tobacco exposure, which could have been from partners or other sources, and it was difficult to differentiate. We included studies that reported a collection of ascertainment of exposure data from maternal charts, interview, and direct or indirect assessments.

Types of outcome measures Studies that reported data on any of the following outcomes were included: (1) LBW birth defined as birthweight ⬍2.5 kg; (2) PTB defined as gestational age ⬍37 weeks; (3) birthweight in grams; (4) gestational age in weeks, and (5) SGA birth defined as birthweight ⬍10th percentile for gestational age. Search strategy for identification of studies Electronic databases (Medline, Embase, and Cumulative Index of Nursing and Allied Health Literature) were searched, with assistance from an experienced librarian, from their inception to March 2009 for all published studies in the English language. The search terms were modified according to database requirements. The reference lists of the identified articles were reviewed to locate additional eligible studies. The articles were scanned initially on the basis of titles and abstracts. The reviewer was not blinded to authors or institution. Selected articles were retrieved in full and were assessed for eligibility. Search terms used were low birthweight; premature birth; preterm birth; small for gestational age; growth, intrauterine; growth restriction, fetal; growth restriction, intrauterine; high risk pregnancy; infant, premature; infant, newborn; pregnancy; familial factors; father, paternal factors, paternal age, paternal birthweight, occupation, education, anthropometry, weight, height, body mass, and body mass index. Methods of the review Data extraction Data from each eligible study were extracted into custom-made data collection forms. Minor modifications (such as combining birthweight means for male and fe104

www.AJOG.org male subjects) and the calculation of raw percentages from available data were done. Confounders that were adjusted for in the analyses in the individual studies were reported. When adjusted data were reported in the primary studies, they were extracted and noted in the results. Assessment of quality of included studies The methodologic quality of studies was assessed with a predefined checklist that was based on criteria for the sample selection, exposure assessment, outcome assessment, confounder, and analytical and attrition biases (Appendix). The classifications were applied in each category: cannot tell, no bias, low risk, moderate risk, or high risk of bias. Data synthesis We expected a significant degree of clinical heterogeneity among studies in each of the paternal factors and planned for a systematic review and not metaanalyses from the outset. Qualitative synthesis of the evidence was planned because of the reasons mentioned earlier. Heterogeneity and publication bias assessment Clinical heterogeneity was assessed and reported in the Tables.

R ESULTS Description of studies Thirty-eight studies were included in this review.5-42 Some of the included studies reported on ⬎1 paternal factor. Paternal alcohol use was identified as an exposure during the literature review (which was not planned a priori). Eleven studies were excluded after detailed evaluation. Details of included studies and reasons for excluded studies are given in Figure 1.43-53 Methodologic quality of included studies The results of the quality assessments of the included studies are reported in Tables 1-6. The studies had low-to-moderate risk of biases. The major criticism of the included studies was that the assessment of exposure in many reports was indirect (such as maternal history, derived or deduced assessment method for

American Journal of Obstetrics & Gynecology FEBRUARY 2010

occupational exposure). Adjustment of confounders was variable among studies; however, compared with other reports of determinants of LBW/PTB births, most of the studies in this category have accounted for common confounders. Assessment of outcomes was satisfactory in most studies. Many studies reported only incidence or percentage of outcome data and not odds ratio or relative risk and their associated confidence interval. The data in the Tables reflect what is reported in the articles. If the risk estimates are missing from a Table, the implication is that they were not reported.

Paternal age There was variability in age cut-offs that were used in the studies as well as the reference age for comparison of groups. Exploratory analysis of a relationship between paternal age and LBW births was conducted. Figure 2 demonstrates the relationship of paternal age (mid values from all reported age groups and conversion of the 25- to 28-year age group as the reference group for each study) and LBW births in 6 studies that reported the odds of LBW births in various age groups. A “saucer-shaped” association can be inferred with higher odds at both extremes. No association between paternal age and PTB or SGA births was identified in any of the studies. Characteristics of the included studies, assessment of biases, and reported results are outlined in Table 1. Paternal height Paternal height showed significant correlation with birthweight of the offspring in most of the studies. On average, there was 125-150 g reduction in birthweight of the offspring of short vs tall fathers. Characteristics of the included studies, assessment of biases, and reported results are given in Table 2. Paternal weight and body mass Most of the studies reported a nonsignificant relationship with paternal body weight or mass and birthweight and LBW births. In 1 study, a significant relationship became nonsignificant when maternal body mass was considered. Characteristics of the included studies,

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FIGURE 1

Flow diagram of included studies. SGA, small for gestational age. Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

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Results Study Abel et al

5,a

Study characteristics

Assessment

Risk of bias

1978-1992; Cohort study performed in North Dakota; used the statewide database; n ⫽ 154,391

Exposure: maternal history

Selection: none

Outcome: birth certificates

Exposure assessment: low

Confounders adjusted: socioeconomic status, maternal age, infant sex, race

Outcome assessment: none Confounding factors: low

Category, y

LBW, OR (95% CI)

PTB, OR (95% CI)

1.00

1.00

1.28 (1.02–1.61)

1.24 (1.02–1.52)

26-30

1.07 (0.85–1.33)

0.89 (0.80–1.00)

31-35

1.03 (0.74–1.44)

0.88 (0.77–1.02)

Analytical: none

36-40

1.26 (0.81–1.96)

1.01 (0.83–1.21)

Attrition: cannot tell

41-45

1.35 (0.77–2.35)

1.12 (0.77–1.33)

21-26

SGA, OR (95% CI)

.............................................................................................................................................................................................................................................................................................................................................................

⬍20

............................................................................................................................................................................................................................................................................................................................................................. ..................................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................................

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Paternal age and relation to low birthweight, preterm, and small-for-gestational-age births

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106 TABLE 1

..................................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................................

Overall: low

⬎45

1.38 (0.71–2.68)

1.12 (0.79–1.57)

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Astolfi et al6,a

1990-1998; Cohort study of nationwide sample from Italy; singleton, first born live births to mothers 20-29 y old and father ⬎20 y old; n ⫽ 1,510,823

Exposure: vital statistics dataset

Selection: none

20-24

1.13 (1.01–1.25)

Outcome: birth certificates

Exposure assessment: low

25-29

1.00

Confounders adjusted: maternal age, infant sex, couple education, birth period

Outcome assessment: none

30-34

1.03 (0.99–1.07)

Confounding factors: low

35-39

1.12 (1.08–1.15)

Analytical: none

40-44

1.23 (1.15–1.31)

45-49

1.16 (0.82–1.65)

............................................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................................. ..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................................

Attrition: low

.....................................................................................................................................................................................................................................................

Overall: low

ⱖ50

1.15 (0.96–1.38)

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Basso and Wilcox7,a,b

1995-2000; Cohort study of national sample from United States; married, non-Hispanic white primiparous women 20-34 y old

Exposure: birth certificate; why are the exposure and outcome the same?

Selection: low

20-24

1.15 (0.94–1.39)

Outcome: birth certificates

Exposure assessment: low

25-29

1.00

Confounders adjusted: maternal education, smoking

Outcome assessment: none

30-34

0.97 (0.93–1.00)

Confounding factors: low

35-39

1.02 (0.97–1.08)

Analytical: none

40-44

1.05 (0.96–1.15)

Attrition: low

45-49

1.15 (0.98–1.34)

............................................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................................. ..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................................

Overall: low

⬎50

Exposure: vital statistics dataset

Selection: none

⬍20

Outcome: birth certificates

Exposure assessment: low

Confounders adjusted: race, maternal age, education, smoking, alcohol, infant sex, prenatal care

Outcome assessment: low

0.97 (0.73–1.29)

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Chen et al8,a

1995-2000; Cohort study performed with nationwide data; 20-29 y-old nulliparous mother who had singleton live birth; n ⫽ 2,520,098

1.13 (1.07–1.19)

1.15 (1.10–1.20)

1.17 (1.13–1.22)

20-29

1.00

1.00

1.00

30-34

1.00 (0.99–1.02)

0.98 (0.07–0.99)

1.03 (1.02–1.04)

Confounding factors: none

35-39

0.99 (0.97–1.02)

0.98 (0.96–1.00)

1.02 (1.00–1.04)

Analytical: none

40-44

0.96 (0.92–1.01)

0.99 (0.95–1.03)

1.02 (0.98–1.06)

45-49

1.01 (0.92–1.10)

1.01 (0.94–1.09)

1.06 (0.99–1.03)

0.91 (0.79–1.05)

0.93 (0.83–1.05)

1.02 (0.92–1.13)

............................................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................................. .....................................................................................................................................................................................................................................................

.....................................................................................................................................................................................................................................................

Attrition: low

.....................................................................................................................................................................................................................................................

Overall: low

ⱖ50

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

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TABLE 1

Paternal age and relation to low birthweight, preterm, and small-for-gestational-age births (continued) Results Study

Study characteristics

Assessment

Risk of bias

Category, y

Nahum and Stanislaw9,a

1998-2000; Cohort study, private single clinic at Duke University; term, uncomplicated, singletons; n ⫽ 241

Exposure: maternal history

Selection: low

Paternal age was not a significant predictor of birthweight if maternal age was specified (P ⫽ .08)

LBW, OR (95% CI)

PTB, OR (95% CI)

SGA, OR (95% CI)

.............................................................................................................................................................................................................................................................................................................................................................

Outcome: charts

Exposure assessment: low

Confounders adjusted: none

Outcome assessment: none

............................................................................................................................................................................................................................................................................................................................................................. .....................................................................................................................................................................................................................................................

Confounding factors: moderate

.....................................................................................................................................................................................................................................................

Analytical: low

.....................................................................................................................................................................................................................................................

Attrition: low

.....................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Olshan et al

10,a

1988-1991; Cohort study of statewide data from North Carolina; 20-34 y-old resident mothers who had singleton live birth; n ⫽ 254,892

⬍19

Selection: low

1.13 (0.97–1.32)

1.23 (1.10–1.39)

1.03 (0.88–1.20)

Outcome: birth files

Exposure assessment: low

20-24

1.04 (0.98–1.09)

1.09 (1.05–1.14)

0.98 (0.93–1.04)

Confounders adjusted: maternal age, race, gravidity, smoking, marital status, education, infant sex

Outcome assessment: low

25-29

1.00

1.00

1.00

Confounding factors: none

30-34

0.96 (0.91–1.01)

0.98 (0.95–1.02)

1.01 (0.96–1.06)

Analytical: low

35-39

0.96 (0.89–1.03)

1.03 (0.97–1.08)

0.95 (0.89–1.03)

Attrition: low

40-44

1.09 (0.97–1.21)

1.05 (0.96–1.14)

1.05 (0.93–1.18)

............................................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................................. ..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................................

Overall: low

45-49

1.00 (0.81–1.23)

1.09 (0.93–1.28)

1.13 (0.92–1.38)

0.81 (0.59–1.12)

1.08 (0.85–1.36)

0.87 (0.63–1.19)

...............................................................................................................................................................................

⬎50

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Reichman and Teitler11,a

1998-2000; Cohort study of randomly selected births from 75 hospitals in the United States; ⬎18 y-old mothers who had singleton live birth; n ⫽ 4621

Exposure: history

Selection: moderate

Outcome: charts

Exposure assessment: low

Confounders adjusted: maternal age, race, gravidity, marital status, socioeconomic status, infant sex

Outcome assessment: none

⬍20

0.7 (0.5–1.0)

.............................................................................................................................................................................................................................................................................................................................................................

20-34

1.00

.............................................................................................................................................................................................................................................................................................................................................................

⬎34

1.7 (1.3–2.2)

.....................................................................................................................................................................................................................................................

Confounding factors: none

.....................................................................................................................................................................................................................................................

Analytical: low

.....................................................................................................................................................................................................................................................

Attrition: none

Obstetrics

.....................................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

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Exposure: birth files

Paternal age and relation to low birthweight, preterm, and small-for-gestational-age births (continued) Results Study

Study characteristics

Assessment

Risk of bias

Category, y

LBW, OR (95% CI)

Selvin and Garfinkel12

1959-1967; Cohort study, singleton live births to white mothers in New York state (excluding New York City); n ⫽ 1,515,443

Exposure: birth certificates

Selection: low

ⱕ19

8.58%

Outcome: birth certificates

Exposure assessment: low

20-24

6.66%

Confounder adjusted: maternal age

Outcome assessment: low

25-29

5.77%

Confounding factors: low

30-34

5.63%

Analytical: low

35-39

6.08%

Attrition: low

40-44

6.57%

PTB, OR (95% CI)

SGA, OR (95% CI)

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..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................................

Overall: low

45-49

7.38%

50-54

7.82%

............................................................................................................................................................................... ...............................................................................................................................................................................

ⱖ55

7.99%

Total

6.13%

ⱕ19

............................................................................................................................................................................... ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Tough et al

13,a

1990-1996; Cohort study, provide wide data from Alberta, Canada; mothers between 25-29 y old; n ⫽ 259,903

Exposure: birth certificates

Selection: none

1.00

1.00

Outcome: birth certificates

Exposure assessment: low

20-24

0.84 (0.74–0.95)

0.87 (0.77–0.97)

Confounder adjusted: maternal age

Outcome assessment: none

25-29

0.82 (0.72–0.93)

0.82 (0.73–0.93)

Confounding factors: low

30-34

0.77 (0.67–0.88)

0.77 (0.68–0.85)

Analytical: low

35-39

0.76 (0.66–0.87)

0.75 (0.66–0.85)

Attrition: low

40-44

0.79 (0.68–0.92)

0.81 (0.71–0.93)

............................................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................................. ..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................................

Overall: low

45-49

0.93 (0.77–1.13)

0.88 (0.74–1.05)

0.98 (0.75–1.26)

0.96 (0.76–1.21)

...............................................................................................................................................................................

ⱖ50

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Zhu et al14,a

1980-1996; Cohort study; singleton live births in Danish fertility database; first child of couple; father ⬍30 y old and ⬎35 y old; n ⫽ 70,347

Exposure: national database

Selection: low

20-24

1.00

Outcome: national database

Exposure assessment: low

25-29

1.1 (0.9–1.2)

Confounders adjusted: maternal age, parity, education, income, infant sex, year of birth

Outcome assessment: low

35-39

1.1 (1.0–1.3)

Confounding factors: none

40-44

1.2 (1.0–1.4)

45-49

1.2 (0.9–1.5)

............................................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................................. ..................................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................................

Analytical: low

.....................................................................................................................................................................................................................................................

Attrition: none

ⱖ50

1.1 (0.8–1.6)

.....................................................................................................................................................................................................................................................

CI, confidence interval; LBW, low birthweight; OR, odds ratio; PTB, preterm; SGA, small-for-gestational-age. a

Results mentioned here are adjusted estimates; b Data for preterm birth at ⬍32 weeks’ gestation.

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

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Overall: low ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

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TABLE 2

Studies of paternal height and offspring birthweight Results Study Cawley et al

Study characteristics 15

1949-1950; Cohort study, singleton, live births and no neonatal death in 2 areas (Smethwick and Birmingham, UK); n ⫽ 1544

Assessment

Risk of bias

Category, cm ⬍168

Birthweight, ga

Exposure: maternal history and measurement

Selection: low

Outcome: charts

Exposure assessment: low

168-173

3307

3239

Confounder adjusted: maternal height

Outcome assessment: none

173-178

3325

Confounding factors: moderate

178-183

3329

............................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................. .................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................

Analytical: low

⬎183

3447

....................................................................................................................................................................................................................................

Attrition: moderate

....................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Klebanoff25,b

1959-1961; Cohort study, singleton, live births from single center in Copenhagen, Denmark; n ⫽ 3130

ⱕ175

Exposure: maternal history

Selection: low

3325

Outcome: charts

Exposure assessment: low

175-178

3413

Confounders adjusted: maternal birthweight, height, weight, smoking, hypertension, education, employment, infant sex, birth order

Outcome assessment: none

179-182

3413

............................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................. ....................................................................................................................................................................................................................................

ⱖ183

Analytical: low

P for trend ⫽ .088

3421

.................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................

Attrition: moderate

....................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Magnus et al

17

1967-1979; Cohort study, singleton, live births who survived neonatal period; data from Norway birth registry; n ⫽ 3130

Exposure: national database

Selection: moderate

Results reported as mean parental height in each 500-g birthweight category; not mean birthweight in each parental height group

.............................................................................................................................................................................................................................................................................................................................................

Outcome: national database

Exposure assessment: low

Confounders adjusted: none

Outcome assessment: none

............................................................................................................................................................................................................................................................................................................................................. ....................................................................................................................................................................................................................................

Confounding factors: moderate

....................................................................................................................................................................................................................................

Analytical: low

....................................................................................................................................................................................................................................

Attrition: cannot tell

....................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

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Confounding factors: none

Studies of paternal height and offspring birthweight (continued) Results Study Miletic et al

Study characteristics 18

2002; Cohort study of all births in the county of Sibenik-Knin, Croatia; n ⫽ 550

Assessment

Risk of bias

Category, cm

Exposure: survey in prenatal clinic

Selection: none

Paternal height correlated significantly with the neonate birthweight (P ⫽ .01)

Birthweight, ga

.............................................................................................................................................................................................................................................................................................................................................

Outcome: hospital record

Exposure assessment: low

Confounders adjusted: none

Outcome assessment: none

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110 TABLE 2

............................................................................................................................................................................................................................................................................................................................................. ....................................................................................................................................................................................................................................

Confounding factors: moderate

....................................................................................................................................................................................................................................

Analytical: low

....................................................................................................................................................................................................................................

Attrition: cannot tell

....................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Morrison et al

19

1980-1996; Cohort study, singleton, live births, term, without anomalies in Queensland University single center study; n ⫽ 8556

Exposure: maternal history

Selection: low

Paternal height was significantly correlated with birthweight (P ⬍ .0007)

.............................................................................................................................................................................................................................................................................................................................................

Outcome: charts

Exposure assessment: low

Confounder adjusted: maternal body mass index

Outcome assessment: none

............................................................................................................................................................................................................................................................................................................................................. ....................................................................................................................................................................................................................................

Confounding factors: moderate

....................................................................................................................................................................................................................................

Analytical: low

....................................................................................................................................................................................................................................

Attrition: cannot tell

....................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Nahum and Stanislaw9,b

See Table 1 for details

Pritchard et al20

1967-1971; Cohort study, singleton, live births in Aberdeen, UK, hospital and associated nursing homes of 32-43 weeks’ gestational age; n ⫽ 5834

Fathers with height ⬎2 SD above and below the mean had 125-g difference in birthweight of index child

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Exposure: direct measurement

Selection: low

SD scores for birthweight were 0.29 higher (approximate correlation of 115-g birthweight) for taller men compared with shorter men

.............................................................................................................................................................................................................................................................................................................................................

Outcome: charts

Exposure assessment: moderate

.............................................................................................................................................................................................................................................................................................................................................

Confounder adjusted: maternal height

Outcome assessment: low

....................................................................................................................................................................................................................................

Confounding factors: moderate

....................................................................................................................................................................................................................................

Analytical: low

.................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

(continued )

www.AJOG.org

Attrition: low

www.AJOG.org

TABLE 2

Studies of paternal height and offspring birthweight (continued) Results Study

Study characteristics

Assessment

Risk of bias

Category, cm

To et al21

1995-1996; Cohort study, singleton, live births of Chinese parents from single center in Hong Kong; ⬎36 weeks’ gestational age; n ⫽ 355

Exposure: direct measurement

Selection: low

Paternal height divided in 5 strata (5 cm for 160-180 cm), significantly correlated with birthweight (P ⬍ .01)

Birthweight, ga

.............................................................................................................................................................................................................................................................................................................................................

Outcome: charts

Exposure assessment: none

Confounders adjusted: maternal prepregnancy weight and height

Outcome assessment: none

............................................................................................................................................................................................................................................................................................................................................. ....................................................................................................................................................................................................................................

Confounding factors: low

....................................................................................................................................................................................................................................

Analytical: low

....................................................................................................................................................................................................................................

Attrition: moderate

....................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Wilcox et al

22,b

1992-1993; Cohort study, singleton, term, live births without congenital anomaly from single center in Nottingham, UK; n ⫽ 571

⬍170

3322 ⫾ 396

Exposure: direct measurement

Selection: low

Outcome: charts

Exposure assessment: none

170-174

3406 ⫾ 473

Confounders adjusted: smoking, maternal height, paternal weight

Outcome assessment: none

175-179

3465 ⫾ 432

Confounding factors: low

180-184

3474 ⫾ 470

185-189

3503 ⫾ 351

............................................................................................................................................................................................................................................................................................................................................. ............................................................................................................................................................................................................................................................................................................................................. .................................................................................................................................................................................................................................... .................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................

Attrition: low

⬎190

3585 ⫾ 378

....................................................................................................................................................................................................................................

Overall: low

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Winikoff and Debrovner23

1992-1993; Cohort study, singleton primiparous, term live births; uncomplicated pregnancies from a single clinic in New York; n ⫽ 259

Exposure: maternal history

Selection: moderate

Paternal height was significantly associated with variations in birthweight (P ⬍ .05)

.............................................................................................................................................................................................................................................................................................................................................

Outcome: charts

Exposure assessment: low

Confounders adjusted: maternal height, paternal weight, maternal prepregnancy weight, weight gain during pregnancy

Outcome assessment: none

............................................................................................................................................................................................................................................................................................................................................. ....................................................................................................................................................................................................................................

Confounding factors: low

....................................................................................................................................................................................................................................

Analytical: low

....................................................................................................................................................................................................................................

Attrition: cannot tell

....................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................ a

Data are given as mean ⫾ SD; Results mentioned here are adjusted estimates. b

111

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Obstetrics

FEBRUARY 2010 American Journal of Obstetrics & Gynecology

Analytical: low

Reviews

Obstetrics

www.AJOG.org

TABLE 3

Studies of paternal weight and body mass index and their relation to birthweight and low birthweight Study characteristics, assessment and risk of biases

Study 25,b

Klebanoff

See Table 2 for details

Results Birthweight, ga

Category ⬍20.08 kg/m

2

3188

.......................................................................................................................................................................................................................................................... 2

20.08-21.56 kg/m

3276

21.57-23.05 kg/m

3261

.......................................................................................................................................................................................................................................................... 2 .......................................................................................................................................................................................................................................................... 2

⬎23.05 kg/m

3293 (P for trend ⫽ .049)

................................................................................................................................................................................................................................................................................................................................................................................ 17

Magnus et al

See Table 2 for details

Results reported as mean parental weight in each 500-g birthweight category; not mean birthweight in each parental weight group

................................................................................................................................................................................................................................................................................................................................................................................ 18

Miletic et al

See Table 2 for details

Paternal bodyweight correlated significantly with the neonate birthweight (P ⫽ .01)

................................................................................................................................................................................................................................................................................................................................................................................ 19

Morrison et al

See Table 2 for details

Paternal weight was not significantly correlated with birthweight (P ⬎ .05)

Nahum and Stanislaw9,b

See Table 1 for details

Paternal weight and BMI were not significant predictor of birthweight once maternal weight (P ⫽ .16) and BMI (P ⫽ .42) were taken in account, respectively

................................................................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................ 21

To et al

See Table 2 for details

Paternal weight divided in 9 strata (5 kg strata for ⬍50 to ⬎90 kg) was not correlated with birthweight (P ⫽ .052); paternal BMI divided in 4 strata (5 kg/m2 strata for ⬍20 to ⬎35 kg/m2) was not correlated with birthweight (P ⫽ .33)

................................................................................................................................................................................................................................................................................................................................................................................ 22,b

Wilcox et al

See Table 2 for details

⬍59 kg

3522 ⫾ 268

..........................................................................................................................................................................................................................................................

60-69 kg

3320 ⫾ 512

70-79 kg

3486 ⫾ 522

80-89 kg

3511 ⫾ 520

90-99 kg

3550 ⫾ 437

100-109 kg

3657 ⫾ 419

.......................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................... ..........................................................................................................................................................................................................................................................

⬎110 kg

3608 ⫾ 373

................................................................................................................................................................................................................................................................................................................................................................................

Winikoff and Debrovner23

See Table 2 for details

Paternal weight was not associated with variations in birthweight (P ⬎ .05)

................................................................................................................................................................................................................................................................................................................................................................................

BMI, body mass index. a

Data are given as mean ⫾ SD; b Results mentioned here are adjusted estimates.

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

assessment of biases, and reported results are given in Table 3.

Paternal birthweight Three studies reported that an infant’s birthweight increased as paternal birthweight increased. The odds of a LBW birth were higher if the father had a LBW birth. Interestingly, 1 study reported higher rates of PTBs as the father’s birthweight increased; however, this might be attributed to maternal characteristic. Characteristics of the included studies, assessment of biases, and reported results are given in Table 4. 112

Paternal occupation Higher and prolonged lead exposures were associated with higher risk of LBW birth and PTB; however, details of timing of exposure in relation to pregnancy were not available in detail to assess direct effect. One large study reported a higher adjusted risk of SGA births among workers who were exposed to benzene, chromium, and other minerals and a higher risk of PTBs among workers who were exposed to x-rays. Other occupations that were assessed were not associated with higher risk of adverse outcomes. Characteristics of the included

American Journal of Obstetrics & Gynecology FEBRUARY 2010

studies, assessment of biases, and reported results are given in Table 5.

Paternal education One study reported a higher risk of LBW births and another reported a higher risk of PTBs among fathers who had a high school education only, compared with fathers who had a college education. Characteristics of the included studies, assessment of biases, and reported results are given in Table 6. Paternal alcohol use One small study reported a 200-g reduction in birthweight with regular alcohol

Paternal birthweight and relation to birthweight, low birthweight, and preterm births Results Author

Study characteristics

Assessment

Risk of bias

Category

Birthweight

Coutinho et al24

1989-91; Cohort study of fathers born from 1956-1975 derived from Illinois vital records; n ⫽ 128,152

Exposure: birth record

Selection: low

Black father LBW

Infant LBW, 14.3%; RR 1.3 (95% CI, 1.1–1.5)

Preterm birth

www.AJOG.org

TABLE 4

...........................................................................................................................................................................................................................................................................................................................................

Outcome: birth certificate

Exposure assessment: low

Black father normal birthweight

Infant LBW, 11.5%

Confounders adjusted: none

Outcome assessment: low

White father LBW

Infant LBW, 5.7%; RR 1.2 (95% CI, 1.0–1.2)

...........................................................................................................................................................................................................................................................................................................................................

............................................................................................................................................................................................................................................

Confounding factors: moderate

White father normal birthweight

Infant LBW, 5.0%

............................................................................................................................................................................................................................................

Analytical: low

............................................................................................................................................................................................................................................

Attrition: cannot tell

............................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Klebanoff et al16

1959-1961; Cohort study, fathers born in this period derived from Danish population register and their singleton, liveborn, children born from 1974-1989; n ⫽ 1258

Exposure: birth record

Selection: low

Outcome: birth certificate

Exposure assessment: moderate

Confounders adjusted: maternal birthweight

Outcome assessment: low

⬍3 kg

5.1%

...........................................................................................................................................................................................................................................................................................................................................

3-3.9 kg

7.1%

...........................................................................................................................................................................................................................................................................................................................................

⬎4 kg

6.9%

............................................................................................................................................................................................................................................

Confounding factors: moderate

............................................................................................................................................................................................................................................

Analytical: low

............................................................................................................................................................................................................................................

Attrition: moderate

............................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Klebanoff25,a

⬍3 kg

See Table 2 for details

3317 g

..................................................................................................................................................................

3-3.9 kg

3384 g

..................................................................................................................................................................

3493 g

..................................................................................................................................................................

P for trend ⫽ .002

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Little26

12-mo period; matched cohort study based on alcohol drinking status, singleton, live births from single center in Copenhagen, Denmark; n ⫽ 377

Exposure: maternal history

Selection: low

Outcome: maternal history

Exposure assessment: low

Confounders adjusted: maternal birthweight

Outcome assessment: none

⬍3 kg

3487 g

...........................................................................................................................................................................................................................................................................................................................................

3-3.999 kg

3555 g

...........................................................................................................................................................................................................................................................................................................................................

⬎4 kg

3707 g

............................................................................................................................................................................................................................................

Confounding factors: moderate

............................................................................................................................................................................................................................................

Analytical: low

............................................................................................................................................................................................................................................

Attrition: moderate

............................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Magnus et al27

1967-1998; Cohort study, singleton, live births from medical birth registry of Norway; n ⫽ 3130

Exposure: birth register

Selection: low

Father normal birthweight

Infant LBW, 2.9%

Outcome: birth register

Exposure assessment: low

Father LBW

Infant LBW, 6.8%

Confounders adjusted: none

Outcome assessment: low

........................................................................................................................................................................................................................................................................................................................................... ........................................................................................................................................................................................................................................................................................................................................... ............................................................................................................................................................................................................................................

Confounding factors: moderate

............................................................................................................................................................................................................................................

Analytical: none

Obstetrics

............................................................................................................................................................................................................................................

Attrition: cannot tell

............................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

CI, confidence interval; LBW, low birthweight, RR, relative risk. a

Results mentioned here are adjusted estimates.

113

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FEBRUARY 2010 American Journal of Obstetrics & Gynecology

⬎4 kg

Results Author

Study characteristics

Exposure and its assessment

Assessment

Risk of bias

Category

LBW, OR (95% CI)

PTB, OR (95% CI)

SGA, OR (95% CI)

Dimich-Ward et al28,a

1952-1988; Cohort study; fathers who worked in saw mills for at least 1 y in British Columbia, Canada; n ⫽ 2128

Chlorophenate wood preservative assessed by calculating exposure time from type of job

Outcome: birth certificate

Selection: low

Up to 3 mo before conception

0.99 (0.99–1.00)

1.00 (0.99–1.00)

1.00 (0.99–1.00)

Exposure assessment: moderate

3 mo before conception

1.01 (0.92–1.08)

Outcome assessment: low

Through entire pregnancy

.........................................................................................................................................................................................................................................................................................................................

Confounders adjusted: maternal and paternal age, infant sex, birth year

0.99 (0.93–1.05)

1.00 (0.96–1.04)

...........................................................................................................................................................................................................................................................

0.99 (0.97–1.01)

0.96 (0.94–0.98)b

1.01 (0.99–1.02)

...........................................................................................................................................................................................................................................................

Obstetrics

American Journal of Obstetrics & Gynecology FEBRUARY 2010

Studies of paternal occupation and low birthweight, preterm, and small-for-gestational-age births

Reviews

114 TABLE 5

Confounding factors: low

...........................................................................................................................................................................................................................................................

Analytical: low

...........................................................................................................................................................................................................................................................

Attrition: cannot tell

...........................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Hooiveld et al29,a

2001; Comparative cohort study; fathers who worked as painters (472 cases) were compared with carpenters (462 control subjects) in The Netherlands; n ⫽ 934

Organic solvents for painters assessed by questionnaire

Outcome: questionnaire

Selection: low

Low level (0.17–0.38)

1.5 (0.5–4.3)

1.6 (0.7–3.9)

Confounders adjusted: maternal age, smoking, alcohol use, chemical exposure; paternal smoking, alcohol use

Exposure assessment: moderate

Intermediate level (0.38–1.02)

1.6 (0.7–3.8)

1.5 (0.7–3.2)

Outcome assessment: low

High level (1.03–4.66)

1.9 (0.9–4.7)

.........................................................................................................................................................................................................................................................................................................................

...........................................................................................................................................................................................................................................................

0.8 (0.3–2.0)

...........................................................................................................................................................................................................................................................

Confounding factors: none

...........................................................................................................................................................................................................................................................

Analytical: none

...........................................................................................................................................................................................................................................................

Attrition: moderate

...........................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Kristensen et al30,a

Male printing workers between 1930-1974 alive at 1960 census; exposure to lead, solvent, and both combined; n ⫽ 6251

Lead and solvent exposure classified based on job codes

Outcome: national birth register

Selection: low

Lead only

0.9 (0.61–1.02)

1.2 (0.93–1.5)

.........................................................................................................................................................................................................................................................................................................................

Confounders adjusted: gestational age, birth order, infant sex, multiple gestation, previous still birth, consanguinity, maternal chronic diseases

Exposure assessment: moderate

Solvents only

1.1 (0.89–1.4)

1.4 (1.1–1.8)

Outcome assessment: none

Lead plus solvent

1.2 (0.92–1.5)

1.2 (0.89–1.5)

Confounding factors: none

Other

1.0

1.0

........................................................................................................................................................................................................................................................... ........................................................................................................................................................................................................................................................... ...........................................................................................................................................................................................................................................................

Analytical: low

...........................................................................................................................................................................................................................................................

Attrition: Cannot tell

...........................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Lawson et al31,a

1987-1988; Matched cohort study; workers from plants in New York and Missouri; matched population selected from neighbors; n ⫽ 1153

2,3,7,8-Tetrachloro-dibenzo-pdioxin assessed from blood sample and modeled calculation

Outcome: birth certificate or maternal report

Selection: low

Reference

Mean birthweight, 3402 g

0.8 (0.6–1.1)

.........................................................................................................................................................................................................................................................................................................................

Confounders adjusted: maternal age, accidents, smoking, alcohol and medication use

Exposure assessment: moderate

⬍20 pg/g

Mean birthweight, 3396 g

...........................................................................................................................................................................................................................................................

Outcome assessment: low

20-254 pg/g

Mean birthweight, 3360 g

...........................................................................................................................................................................................................................................................

⬎255 pg/g

Mean birthweight, 3485 g

...........................................................................................................................................................................................................................................................

Analytical: low

...........................................................................................................................................................................................................................................................

Attrition: moderate

...........................................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

(continued )

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Confounding factors: moderate

Studies of paternal occupation and low birthweight, preterm, and small-for-gestational-age births (continued) Results Author

Study characteristics

Exposure and its assessment

Assessment

Risk of bias

Category

LBW, OR (95% CI)

PTB, OR (95% CI)

SGA, OR (95% CI)

Lin et al32,a

1981-1992; Matched cohort study; fathers exposed to high lead levels (⬎40 ␮g/dL before 1986 and ⬎25 ␮g/dL after 1986 (n ⫽ 747) compared with male bus drivers (n ⫽ 2259) in New York, 1974-1989 (n ⫽ 1258)

Lead exposure assessed from laboratory reports of workers

Outcome: birth certificate

Selection: low

General exposure (risk ratio)

1.00 (0.67–1.50)

0.89 (0.64–1.26)

0.86 (0.64–1.15)

Confounders adjusted: paternal age, maternal education, maternal complications, prenatal care, race, parity, infant sex

Exposure assessment: low

Lead exposure for ⬎5 years (risk ratio)

3.40 (1.39–8.35)b

3.03 (1.35–6.77)b

0.82 (0.28–2.37)

www.AJOG.org

TABLE 5

.........................................................................................................................................................................................................................................................................................................................

...........................................................................................................................................................................................................................................................

Outcome assessment: none

...........................................................................................................................................................................................................................................................

Confounding factors: none

...........................................................................................................................................................................................................................................................

Analytical: low

...........................................................................................................................................................................................................................................................

Attrition: cannot tell

...........................................................................................................................................................................................................................................................

Overall: low

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Michalek et al33

1961-1971; Matched cohort study; children of fathers exposed to herbicide spray during Vietnam conflict (n ⫽ 859) compared with children of unexposed Air Force veterans (n ⫽ 1223); n ⫽ 2082

2,3,7,8-Tetrachloro-dibenzo-pdioxin assessed from blood sample and modeled calculation

Outcome: charts

Selection: low

Control (ⱕ10 ppt)

1.0

1.0

Confounders adjusted: none

Exposure assessment: moderate

Cases (ⱕ10 ppt)

1.4 (0.9–2.3)

0.9 (0.6–1.4)

Outcome assessment: none

Low (⬍79 ppt)

0.5 (0.2–1.2)

0.9 (0.6–1.3)

Confounding factors: moderate

High (ⱖ79 ppt)

1.3 (0.8–2.3)

0.9 (0.6–1.3)

.........................................................................................................................................................................................................................................................................................................................

........................................................................................................................................................................................................................................................... ...........................................................................................................................................................................................................................................................

...........................................................................................................................................................................................................................................................

Analytical: low

...........................................................................................................................................................................................................................................................

Attrition: moderate

...........................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

1980-2002; Cohort study; fathers who were flour mill workers in Washington state; n ⫽ 59

Fumigants used to kill insects, mainly methyl bromide and phosphine; assessed by history of work-related exposure

Outcome: birth certificate

Selection: low

Unexposed (male children)

Mean birthweight, 3511 g

.........................................................................................................................................................................................................................................................................................................................

Confounders adjusted: none

Exposure assessment: moderate

Unexposed (female children)

Outcome assessment: none

Exposed (male children)

Mean birthweight, 3389 g

...........................................................................................................................................................................................................................................................

Mean birthweight, 3180 g

...........................................................................................................................................................................................................................................................

Confounding factors: moderate

Exposed (female children)

Mean birthweight, 3602 g

...........................................................................................................................................................................................................................................................

Analytical: moderate

...........................................................................................................................................................................................................................................................

Attrition: cannot tell

...........................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Min et al35

1981-1989; Case control study; control subjects enrolled in another study in BaltimoreWashington DC; cases (n ⫽ 220) were LBW; controls were not LBW (n ⫽ 522); n ⫽ 742

Lead exposure assessed by history regarding type of job and hours exposed

Outcome: birth certificate

Selection: low

No exposure

1.0

Confounders adjusted: none

Exposure assessment: low

Threshold, ⱕ0.01

0.70 (0.37–1.27)

Outcome assessment: none

Threshold, ⬎0.1 to ⬍0.5

1.67 (0.65–4.30)

Confounding factors: moderate

Threshold, ⱖ0.5

4.7 (1.1–20.2)b

......................................................................................................................................................................................................................................................................................................................... ........................................................................................................................................................................................................................................................... ...........................................................................................................................................................................................................................................................

........................................................................................................................................................................................................................................................... ...........................................................................................................................................................................................................................................................

Attrition: low

...........................................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

(continued )

115

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Analytical: moderate

Obstetrics

FEBRUARY 2010 American Journal of Obstetrics & Gynecology

Milham and Ossiander34

Studies of paternal occupation and low birthweight, preterm, and small-for-gestational-age births (continued) Results Author

Study characteristics

Exposure and its assessment

Assessment

Risk of bias

Category

LBW, OR (95% CI)

PTB, OR (95% CI)

Mjoen et al36,a

1976-1995; Cohort study; all births in national registry of Norway where exposure risk can be determined; n ⫽ 28,435

Radiofrequency fields exposure assessed based on type of occupation

Outcome: birth certificate

Selection: low

Probably unexposed

1.00

1.00

Exposure assessment: moderate

Possibly exposed

0.99 (0.96–1.02)

1.03 (0.98–1.07)

Outcome assessment: none

Probably exposed

SGA, OR (95% CI)

Obstetrics

American Journal of Obstetrics & Gynecology FEBRUARY 2010

Reviews

116 TABLE 5

.........................................................................................................................................................................................................................................................................................................................

Confounders adjusted: calendar year, place of birth, education

...........................................................................................................................................................................................................................................................

1.08 (1.03–1.15)b

1.03 (0.94–1.13)

...........................................................................................................................................................................................................................................................

Confounding factors: low

...........................................................................................................................................................................................................................................................

Analytical: none

...........................................................................................................................................................................................................................................................

Attrition: cannot tell

...........................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Sanjose et al37

1981-1984; Cohort study in Scotland, regarding parental occupation and liveborn infants; n ⫽ 177,746

Classified as manual and nonmanual jobs; no direct assessment of any exposure

Outcome: birth certificate

Selection: none

Nonmanual

3.8%

3.9%

3.4%

Confounders adjusted: none

Exposure assessment: moderate

Manual; potential hazard

5.1%

4.5%

4.7%

Outcome assessment: none

Manual; other

.........................................................................................................................................................................................................................................................................................................................

...........................................................................................................................................................................................................................................................

6.0%

5.2%

5.6%

...........................................................................................................................................................................................................................................................

Confounding factors: moderate

...........................................................................................................................................................................................................................................................

Analytical: none

...........................................................................................................................................................................................................................................................

Attrition: cannot tell

...........................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Savitz et al38,a,c

1980; Cohort study; “National Natality Study” in United States; n ⫽ 177,746

Paternal occupations held within 12 mo of birth

1.5 (1.0–2.3)b

Outcome: birth certificate

Selection: low

X-ray

Confounders adjusted: maternal smoking, race, infant sex

Exposure assessment: moderate

Benzene

Outcome assessment: none

Chromium

1.4 (1.0–1.9)b

Confounding factors: low

Minerals and compounds

1.3 (1.0–1.8)b

.........................................................................................................................................................................................................................................................................................................................

1.5 (1.1–2.3)b

........................................................................................................................................................................................................................................................... ........................................................................................................................................................................................................................................................... ...........................................................................................................................................................................................................................................................

Analytical: none

...........................................................................................................................................................................................................................................................

Attrition: cannot tell

...........................................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

CI, confidence interval; LBW, low birthweight; OR, odds ratio; ppt, parts per trillion; PTB, preterm; SGA, small-for-gestational-age. a

Results mentioned here are adjusted estimates; b Only data which were significant are reported here; c Only significant results are reported; all other occupations had nonsignificant relationships.

www.AJOG.org

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

www.AJOG.org

TABLE 6

Miscellaneous paternal factors and low birthweight, preterm, and small-for-gestational-age births Results Study

Study characteristics

Assessment

Risk of bias

Category

LBW, OR (95% CI)

PTB, OR (95% CI)

SGA, OR (95% CI)

PATERNAL EDUCATION Abel et al5,a

See Table 1 for details

Less than high school

9.3% male; 8.4% female

.......................................................................................................................................................................................

High school

5.5% male; 7.8% female

.......................................................................................................................................................................................

College

6.3% male; 5.5% female

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Parker and Schoendorf39

1984-1988; Cohort study; natality data from 47 states; singleton live births to married white or black women ⬎17 y old; n ⫽ 9,740,852

Exposure: national database

Selection: low

Less than high school

1.53 (1.51–1.55)

Outcome: national database

Exposure assessment: moderate

High school graduate

1.28 (1.27–1.30)

Confounders adjusted: maternal race, age, parity, education

Outcome assessment: none

Some college

1.14 (1.12–1.15)

Confounding factors: low

College graduate

1.00

.................................................................................................................................................................................................................................................................................................................................................................. .................................................................................................................................................................................................................................................................................................................................................................. ................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................

Analytical: none

................................................................................................................................................................................................................................................................

Attrition: low

................................................................................................................................................................................................................................................................

Overall: moderate

PATERNAL ALCOHOL USE Little26

See Table 4 for details

Occasional

Mean birthweight, 3646 g

Mean gestational age, 41.2 wk

Mean birthweight, 3465 g

Mean gestational age, 40.5 wk

.......................................................................................................................................................................................

Regular

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Passaro et al40

1991-1992; Cohort study; Avon County, England; singleton live births; n ⫽ 7756

Exposure: questionnaire

Selection: none

Outcome: hospital records

Exposure assessment: none

None

5.6%

6.4%

Confounders adjusted: gestational age, infant sex, primiparity, maternal smoking, maternal body mass index, maternal race, maternal education, maternal age, marital status, marijuana use, caffeine use, alcohol intake

Outcome assessment: none

Less than weekly

4.1%

5.7%

Confounding factors: none

Weekly

..................................................................................................................................................................................................................................................................................................................................................................

NA

.................................................................................................................................................................................................................................................................................................................................................................. ................................................................................................................................................................................................................................................................

3.5%

5.4%

Analytical: none

1-2 drinks/d

4.4%

5.9%

Attrition: moderate

3⫹ drinks/d

4.3%

6.5%

................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................

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Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

(continued )

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118 TABLE 6

Miscellaneous paternal factors and low birthweight, preterm, and small-for-gestational-age births (continued) Results Study

Study characteristics

Assessment

Risk of bias

Category

Exposure: history

Selection: low

No alcohol

Outcome: charts

Exposure assessment: low

Confounders adjusted: parental smoking, maternal alcohol use, race, education, prenatal care, infant sex

Outcome assessment: none Confounding factors: low Analytical: low

LBW, OR (95% CI)

PTB, OR (95% CI)

SGA, OR (95% CI)

PATERNAL ALCOHOL USE (continued) Savitz et al41

1959-1966; Cohort study, San Francisco, CA; singleton live births to married women; n ⫽ 10,232

1.0

1.0

0-0.5 drinks/d

0.9 (0.7–1.1)

1.0 (0.8–1.3)

0.5-1 drinks/d

1.1 (0.8–1.4)

1.0 (0.7–1.4)

1-1.5 drinks/d

0.8 (0.6–1.1)

1.2 (0.9–1.6)

1.5-2 drinks/d

1.0 (0.7–1.5)

0.9 (0.5–1.4)

0.8 (0.5–1.3)

1.1 (0.7–1.7)

.................................................................................................................................................................................................................................................................................................................................................................. .................................................................................................................................................................................................................................................................................................................................................................. ................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................

Attrition: moderate

⬎2 drinks/d

................................................................................................................................................................................................................................................................

Overall: moderate

............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

Windham et al42

1986-1987; Control arm of a case-control study, California; singleton live births; n ⫽ 1252

Exposure: interview

Selection: none

No alcohol

7.3%

14.8%

8.0%; AOR, 1.0 (Reference)

..................................................................................................................................................................................................................................................................................................................................................................

Outcome: birth certificate

Exposure assessment: none

1-13 drinks/wk

7.1%

14.0%

9.3%; AOR, 1.2 (0.7–1.9)

..................................................................................................................................................................................................................................................................................................................................................................

Confounders adjusted: maternal age, race, parity, marital status, education, employment status, insurance status, caffeine consumption, cigarette smoking, hypertension, infant sex

Outcome assessment: none

14-20 drinks/wk

2.7%

10.8%

13.5%; AOR, 1.3 (0.5–2.9)

................................................................................................................................................................................................................................................................

Confounding factors: none

ⱖ21 drinks/wk

9.6%

17.8%

16.4%; AOR, 1.4 (0.7–1.9)

................................................................................................................................................................................................................................................................

Analytical: low

................................................................................................................................................................................................................................................................

Attrition: none

................................................................................................................................................................................................................................................................

Overall: moderate ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

AOR, adjusted odds ratio; CI, confidence interval; LBW, low birthweight; NA, not available; OR, odds ratio; PTB, preterm; SGA, small-for-gestational-age. a

Results mentioned here are adjusted estimates.

Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

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www.AJOG.org use; other studies reported no difference in the risk of LBW birth or PTBs with different levels of paternal alcohol use.26,40-42 Characteristics of the included studies, assessment of biases, and reported results are given in Table 6.

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FIGURE 2

C OMMENT In this systematic review of 36 studies on paternal factors and birth outcomes, certain positive and negative associations were observed. Extreme paternal ages (⬍20 and ⬎40 years) may be associated with LBW; however, no consistent associations with PTBs and SGA births were identified. Paternal height and paternal occupational exposure to lead were associated with LBW and birthweight of the offspring. The infant’s birthweight increased with a higher paternal birthweight. Paternal weight, body mass, and occupational exposures to herbicides, plant work, woodwork and paternal alcohol use were not associated with birth outcomes. A lower level of paternal education was associated with LBW/PTB and SGA births; however, confirmation of data from larger studies is warranted.

Paternal age Advanced paternal age has been linked with fetal loss,54 congenital malformations,55 single gene disorders,56 lower intelligence, dyslexia,57 and mental disorders58 in children. Studies of the impact of paternal age on LBW, PTB, or SGA outcomes have concluded varied results.5,6,10,14 Biologic rationale behind the influence of paternal age on birth outcomes stems from the identification of greater expression of paternal genes on the placenta59 and higher chances of mutation that involves those genes in immature men compared with mature men60 and in men of advanced age.61 A paternal “weathering” phenomenon (ie, biologic effects of male aging that is hastened by harsh living conditions over years) has been suspected.11 The overall impression from our systematic review of included studies and the plot of paternal age–LBW birth incidence curve suggest that, if there was an effect of paternal age on LBW birth, it would appear to be modest for advanced paternal age.

Scatter plot of paternal age and odds ratio for low birthweight (LBW ) births that were reported in various age groups. Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

Paternal anthropometry All 10 reviewed studies reported an increase in birthweight as father’s height increased. The magnitude of increase between the lowest group and the highest group was approximately 125-150 g. No studies reported incidences of LBW, PTB, or SGA births. The effect is presumed to be of genetic origin.21 Studies of paternal weight and its influence on birthweight revealed contradictory results. Two studies reported an approximate 75- to 100-g increase in birthweight among the highest weight/body mass index group,22,25 compared with the lowest weight/body mass index group. Three studies reported no significant influence.9,19,21 All of these studies had very small sample sizes, and a large population-based study is warranted. Paternal birthweight Lower paternal birthweight was associated with lower infant birthweight. Paternal LBW was associated with higher risk of an infant with LBW, which is an effect that is similar to maternal LBW.

PTB rate was lower for fathers in the LBW birth category. However, this information comes from very few and small studies. Ascertainment issues regarding birthweight of the father should not be ignored in the interpretation of these results. Also, studies from different countries were included in this review; therefore, it may have affected the results because there are different norms for birthweight in different ethnic backgrounds.

Paternal occupational exposure There are 2 pathways by which paternal exposure contribute to an effect on birth outcomes: either paternal exposure leads to maternal exposure and the effect is exerted or paternal exposure leads to alteration in the germ cell line that leads to either increased infertility or abnormality in conception.3 Lead, dioxin, and organic solvents are the more commonly studied exposures. Animal experiments reported lower birthweight after male animal exposure to lead.62 Lead exposure has been shown to be associated

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119

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with infertility, still births, and spontaneous abortions.38 The effect is suspected to be due to effects on the metabolic activity of the sperm.63 Higher and prolonged exposure to lead may be associated with increased risk of LBW births and PTBs; however, ascertainment bias played a major role in included studies. Agent Orange was a widely used herbicide in Vietnam, and contamination of this by dioxin prompted a series of studies that explored the association of paternal exposure with birth outcomes.31 Two studies reported no significant association between exposure to dioxin and LBW birth or PTB.31,33 Organic solvents can pass the blood-testis barrier and the placenta. Two studies of this association revealed no significant association.29,30 Several studies of occupational exposure assessment have classified exposure based on interviews, databases, and expected hours of exposure.28-31,34 The possibility of misclassification and recall bias cannot be ruled out.

Other paternal factors Paternal alcohol intake was not associated significantly with PTB/SGA births in 1 study,41 but another study reported a 180-g increase in mean birthweight among offspring of the occasional drinker, compared with regular drinkers.48 The biologic rationale for such an effect remains to be understood. Less than a high school education was associated with a higher rate of PTB, and education less than college level was associated with higher odds of LBW births. Paternal low education level may be a marker for other underlying health determinants such as poverty, adverse home environment, and associated stress. There was significant heterogeneity in the reported studies that assessed paternal factors and its association to offspring outcomes. Keeping this in mind, we planned for a systematic review from the onset and not metaanalyses. Major clinical heterogeneities among studies were identified for inclusion of the studies (single institution-based study vs national sample) and for adjustment of confounders (different studies controlled for different confounders). A 120

www.AJOG.org number of studies identified associations in univariate analyses; however, when confounders such as maternal factors were considered, the association became nonsignificant. The major issues with parental occupational exposure were ascertainment of a bias for exposure and recall bias. Strengths of this systematic review lie in the focused question, comprehensive and extensive literature search, and inclusion of studies from various countries. However, there are limitations of this review. First, there was heterogeneity in studies even within various exposure categories. Second, data on paternal factors are not collected regularly because fathers may not be present at prenatal visits and data are collected from mothers. The information that is collected could be subject to inaccuracies. Additionally, occupational exposure data were obtained from administrative databases or calculated in terms of duration or intensity of exposure. This is subject to ascertainment bias. Additionally, no detailed information regarding the timing of exposure and the protection used by fathers were reported. Third, various studies adjusted for different confounders in their analyses, and some studies did not adjust for confounders. It is important to adjust for various maternal confounders to assess the independent effect of paternal exposure. This limited our ability to conclude anything definitively about any of the factors. Fourth, publication bias should be considered. There is a possibility that, if the studies reported no association for any of the paternal exposures, there may have been less likelihood of publication. Fifth, we restricted our search to English language publications primarily because of the scope of information that may or may not be available in other languages. Literature searchers have found minimal difference with the inclusion of nonEnglish language articles.64 We have not included gray literature, abstracts, and proceedings because the quality of such studies cannot be assessed adequately. Finally, none of the studies used any objective measure to confirm

American Journal of Obstetrics & Gynecology FEBRUARY 2010

paternity; the data on paternity were obtained from maternal history in all studies.

Implications There are clinically significant and important implications of these results. Pregnancies that were conceived from younger and advanced age fathers, short-statured fathers, fathers who were LBW at birth, and fathers with less than a college education could be considered to be at a greater risk. This information can be used during counseling and education sessions. Conclusion In this comprehensive systematic review of paternal factors, associations were identified for paternal age, height, and LBW. Higher paternal birthweight resulted in heavier offspring. Heavy and prolonged lead exposure may be associated with LBW. Paternal weight, body mass, and workers with occupational exposures to herbicides, plant work, and wood were not associated with birth outcomes. Low paternal education may be associated with LBW/PTB births; however, further studies are warranted. f ACKNOWLEDGMENTS We sincerely thank Elizabeth Uleryk, Chief Librarian at the Hospital for Sick Children, Toronto, for her contribution in developing search strategy and running searches on a periodic basis, for which she did not receive any compensation. Contributors: guarantor: Shah PS; grant concept and design: all members of the group; study concept and design: Shah PS; acquisition of data, analysis, and interpretation of data, drafting of the manuscript: Shah PS; critical revision of the manuscript for intellectual content: Shah PS and all members of group. Members of the Knowledge Synthesis Group on determinants of LBW/preterm births: Prakesh S Shah, University of Toronto, Toronto, Ontario, Canada; Arne Ohlsson, University of Toronto, Ontario, Canada; Sarah D McDonald, McMaster University, Hamilton, Ontario, Canada; Eileen Hutton, McMaster University, Hamilton, Ontario, Canada; Vibhuti Shah, University of Toronto, Toronto, Ontario, Canada; Joseph Beyene, University of Toronto, Toronto, Ontario, Canada; Corine Frick, University of Calgary, Calgary, Alberta, Canada; Fran Scott, University of Toronto, Toronto, Ontario, Canada; Kellie E Murphy, University of Toronto, Ontario, Canada; Christine Newburn-Cook, University of Alberta, Edmonton, Alberta, Canada; Victoria

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www.AJOG.org Allen, Dalhousie University, Halifax, Nova Scotia, Canada.

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dation, and infant death. Epidemiology 1998;9:161-7. 34. Milham S, Ossiander EM. Low proportion of male births and low birth weight of sons of flour mill worker fathers. Am J Ind Med 2008;51: 157-8. 35. Min YI, Correa-Villasenor A, Stewart PA. Parental occupational lead exposure and low birth weight. Am J Ind Med 1996;30:569-78. 36. Mjoen G, Saetre DO, Lie RT, et al. Paternal occupational exposure to radiofrequency electromagnetic fields and risk of adverse pregnancy outcome. Eur J Epidemiol 2006;21: 529-35. 37. Sanjose S, Roman E, Beral V. Low birthweight and preterm delivery, Scotland, 198184: effect of parents’ occupation. Lancet 1991;338:428-31. 38. Savitz DA, Whelan EA, Kleckner RC. Effect of parents’ occupational exposures on risk of stillbirth, preterm delivery, and small-for-gestational-age infants. Am J Epidemiol 1989; 129:1201-18. 39. Parker JD, Schoendorf KC. Influence of paternal characteristics on the risk of low birth weight. Am J Epidemiol 1992;136:399-407. 40. Passaro KT, Little RE, Savitz DA, Noss J. Effect of paternal alcohol consumption before conception on infant birth weight: ALSPAC Study Team: Avon Longitudinal Study of Pregnancy and Childhood. Teratology 1998;57: 294-301. 41. Savitz DA, Zhang J, Schwingl P, John EM. Association of paternal alcohol use with gestational age and birth weight. Teratology 1992; 46:465-71. 42. Windham GC, Fenster L, Hopkins B, Swan SH. The association of moderate maternal and paternal alcohol consumption with birthweight and gestational age. Epidemiology 1995;6: 591-7. 43. Aschengrau A, Monson RR. Paternal military service in Vietnam and the risk of late adverse pregnancy outcomes. Am J Public Health 1990;80:1218-24. 44. Jaquet D, Swaminathan S, Alexander GR, et al. Significant paternal contribution to the risk of small for gestational age. BJOG 2005; 112:153-9. 45. Joffe JM, Soyka LF. Paternal drug exposure: effects on reproduction and progeny. Semin Perinatol 1982;6:116-24. 46. Lie RT, Wilcox AJ, Skjaerven R. Maternal and paternal influences on length of pregnancy. Obstet.Gynecol 2006;107:880-5. 47. Little RE, Sing CF. Association of father’s drinking and infant’s birth weight. N Engl J Med 1986;314:1644-5. 48. Little RE, Sing CF. Father’s drinking and infant birth weight: report of an association. Teratology 1987;36:59-65. 49. Rubin DH, Leventhal JM, Krasilnikoff PA, Weile B, Berget A. Father’s drinking (and smoking) and infant’s birth weight. N Engl J Med 1986;315:1551.

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60. Schwartz D, Mayaux MJ, Spira A, et al. Semen characteristics as a function of age in 833 fertile men. Fertil Steril 1983;39:530-5. 61. Crow JF. The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet 2000;1:40-7. 62. Stowe HD, Goyer RA. Reproductive ability and progeny of F 1 lead-toxic rats. Fertil Steril 1971;22:755-60. 63. Jager S. Sperm nuclear stability and male infertility. Arch Androl 1990;25:253-9. 64. Moher D, Pham B, Lawson ML, Klassen TP. The inclusion of reports of randomised trials published in languages other than English in systematic reviews. Health Technol Assess 2003;7:1-90.

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APPENDIX

Quality assessment tool Cannot tell

Bias

None

Low

Moderate

High

Selection

Consecutive unselected population

Sample selected from large population; selection criteria not defined

Sample selection ambiguous; sample may be representative

Sample selection ambiguous; sample likely not representative

NA

A select group of population (eg, based on race, ethnicity, residence)

Eligibility criteria not explained

A very select population was studied, which made it difficult to generalize findings

NA

..........................................................................................................................................................................................................................................................................................................................................

Sample selected from general population rather than a select group

..........................................................................................................................................................................................................................................................................................................................................

Rationale for case and control selection explained

Rationale for case and control subjects not explained

NA

Follow-up or assessment time explained

Follow-up or assessment time not explained

NA

..........................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

Exposure assessment

Direct questioning (interview) or completion of survey by mother at the time of exposure or close to the time of exposure

Assessment of exposure from global dataset

Direct measurement of exposure (laboratory)

Indirect assessment (postal survey, mailed questionnaire)

Extrapolating data from population exposure sample (with some assumptions) and not direct assessment at any time

Indirect method of assessment (obtaining data from others and not from mother or father)

NA

..........................................................................................................................................................................................................................................................................................................................................

NA

................................................................................................................................................................................................................................................................................................................................................................................

Outcome assessment

Assessment from hospital record, birth certificate, or direct question to mother regarding birthweight

Assessment from administrative database

Assessment from “open-ended” questions (was your baby early? or premature? or small? or before due date)

Assessment from nonvalidated sources or generic estimate from overall population

NA

..............................................................................................................................................................................................................................................................

Direct question to mother regarding gestational age

NA

................................................................................................................................................................................................................................................................................................................................................................................

Confounding factor

Controlled for common confounders

Only certain confounders adjusted

Not controlled for confounders

Analytical

Analyses appropriate for the type of sample

Analyses not accounting for common statistical adjustment (eg, multiple analyses) when appropriate

Sample size estimation unclear, or only subsample of eligible patients was studied

NA

................................................................................................................................................................................................................................................................................................................................................................................

Analyses inappropriate for the type of sample/study

NA

..........................................................................................................................................................................................................................................................................................................................................

Analytical method accounted for sampling strategy in cross-sectional study

Sample size calculation not performed; all available eligible patients studied

NA

Sample size calculation performed and adequate sample studied

Sample size calculated; reasons for not meeting sample size given

NA

0-10% attrition and reasons for loss of follow-up data explained

0-10% attrition and reasons for loss of follow-up data not explained

11-20% attrition; reasons for loss of follow-up data not explained

All subjects from initiation of study to the final outcome assessment were accounted for

11-20% attrition; reasons for loss of follow-up data explained

⬎20% attrition but reasons for loss of follow up explained

NA

All subjects from initiation of study to final outcome assessment not accounted for

NA

..........................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

Attrition

⬎20% attrition; reasons for loss of follow-up data not explained

NA

..........................................................................................................................................................................................................................................................................................................................................

.....................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

NA, information was not available from published report. Shah. Paternal factors and LBW/PTB. Am J Obstet Gynecol 2010.

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