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The association between obstetrical interventions and late preterm birth
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The association between obstetrical interventions and late preterm birth Kate L. Bassil, PhD; Abdool S. Yasseen III, MSc; Mark Walker, MD; Michael D. Sgro, MD; Prakesh S. Shah, MD; Graeme N. Smith, MD, PhD; Douglas M. Campbell, MD; Muhammad Mamdani, PharmD; Ann E. Sprague, PhD; Shoo K. Lee, MD; Jonathon L. Maguire, MD OBJECTIVE: There is concern that obstetric interventions (prelabor cesarean section and induced delivery) are drivers of late preterm (LP) birth. Our objective was to evaluate the independent association between obstetric interventions and LP birth and explore associated independent maternal and fetal risk factors for LP birth. STUDY DESIGN: In this population-based cross-sectional study, the
BORN Information System was used to identify all infants born between 34 and 40 completed weeks of gestation between 2005 and 2012 in Ontario, Canada. The association between obstetric interventions (preterm cesarean section and induced delivery) and LP birth (34 to 36 completed weeks’ gestation vs 37 to 40 completed weeks’ gestation) was assessed using generalized estimating equation regression. RESULTS: Of 917,013 births between 34 and 40 weeks, 49,157 were
LP (5.4%). In the adjusted analysis, “any obstetric intervention” (risk
ratio [RR], 0.65; 95% confidence interval [CI], 0.57e0.74), induction (RR, 0.71; 95% CI, 0.61e0.82) and prelabor cesarean section (RR, 0.66; 95% CI, 0.59e0.74) were all associated with a lower likelihood of LP vs term birth. Several independent potentially modifiable risk factors for LP birth were identified including previous cesarean section (RR, 1.28; 95% CI, 1.16e1.40), smoking during pregnancy (RR, 1.28; 95% CI, 1.21e1.36) and high material (RR, 1.1; 95% CI, 1.03e1.18) and social (RR, 1.09; 95% CI, 1.02e1.16) deprivation indices. CONCLUSION: After accounting for differences in maternal and fetal risk,
LP births had a 35% lower likelihood of obstetric interventions than term births. Obstetric care providers may be preferentially avoiding induction and prelabor cesarean section between 34 and 37 weeks’ gestation. Key words: cesarean delivery, late preterm, maternal health, obstetric intervention, risk factors
Cite this article as: Bassil KL, Yasseen III AS, Walker M, et al. The association between obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014;210:x-ex-x-ex.
P
reterm birth is the leading cause of infant morbidity and mortality and has been described as the most important perinatal challenge facing industrialized countries.1 Among preterm infants (<37 weeks’ of gestation), “late preterm” (LP) infants (born between 340 and 366 weeks of gestation) account for the largest proportion (74%) and are the fastest growing subgroup.1,2 Children born LP are at greater risk than term
infants (37 weeks) for numerous short and long-term adverse outcomes.3-7 Two groups of LP birth have been defined by their etiology: spontaneous LP births (ie, premature labor with intact membranes or preterm prelabor rupture of membranes), and LP births because of obstetric intervention (ie, induction of labor or cesarean section).8 There
is concern that obstetric interventions may be driving the increase in LP birth in recent years and are responsible for a substantial proportion of LP births.9,10 Understanding the independent contribution of obstetric interventions in the context of maternal and fetal risk factors for LP birth has been challenging largely owing to limitations in population based data on maternal and fetal risk factors for LP birth.
From the Maternal-Infant Care Research Institute (Drs Bassil, Lee, and Shah) and the Department of Pediatrics (Drs Shah and Lee), Mount Sinai Hospital; Li Ka Shing Knowledge Institute (Drs Sgro, Campbell, Mamdani, and Maguire) and the Department of Pediatrics (Drs Sgro, Campbell, and Maguire), St. Michael’s Hospital; Department of Pediatrics, Faculty of Medicine (Drs Sgro, Shah, Lee, and Maguire), and Leslie Dan Faculty of Pharmacy (Dr Mamdani), University of Toronto, Toronto; BORN Ontario (Better Outcomes Registry & Network) (Mr Yasseen and Drs Walker and Sprague), and Department of Obstetrics and Gynecology (Mr Yasseen and Dr Walker), Ottawa Hospital Research Institute, and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa; and Department of Obstetrics and Gynecology (Dr Smith), Faculty of Medicine, Queen’s University, Kingston, ON, Canada. Received Nov. 6, 2013; revised Jan. 10, 2014; accepted Feb. 24, 2014. The authors report no conflict of interest. Financial support for this project was supplied by Physician’s Services Incorporated Foundation, the St. Michael’s Hospital Academic Funding Plan Innovation Fund and the St. Michael’s Foundation. Reprints: Jonathon Maguire, Department of Pediatrics, St. Michael’s Hospital, 30 Bond St., 15CC-014, Toronto ON M5B 1W8. jonathon.maguire@ utoronto.ca. 0002-9378/free ª 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2014.02.023
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The objective of this study was to evaluate the magnitude and direction of the association between obstetric interventions (induced delivery and cesarean section) and LP birth (relative to term birth) in the context of known risk factors for preterm birth. We also aimed to explore the magnitude of the associations between maternal and fetal risk factors for LP birth, independent of obstetric interventions, which could be targets for interventions to prevent LP birth.
M ETHODS This was a population-based cohort study of pregnant women in Ontario, Canada, between April 1, 2005, and March 31, 2012.
Study population All women who gave birth in a hospital to a live infant >500 g birthweight with a gestational age between 340/7 and 406/7 weeks in Ontario, Canada, between 2005 and 2012 were eligible for inclusion in this study. Women who gave birth between 410/7 and 416/7 weeks’ gestation were excluded to avoid capturing an increased risk of obstetric interventions in the 41st week of gestation. Sources of data Data were obtained from the BORN Information System (BIS), which is a provincial, internet-based maternal newborn surveillance system managed by the Better Outcomes Registry & Network (BORN Ontario). Maternal, fetal, and obstetric data were extracted for the study time period, April 1, 2004, to March 31, 2012. In a birth number validation exercise between the CIHI Discharge Abstract Database and the BIS, the BORN system captured 82% of hospital births in the 2004-2005 fiscal year and increased yearly until 100% of hospital births from 106 sites were captured by 2010-11. The BIS includes information on maternal demographic characteristics and health behaviors, preexisting maternal health problems, obstetric complications, intrapartum interventions, and birth outcomes. Various quality assurance mechanisms were used to ensure high data quality and consistency including data entry operating
www.AJOG.org manuals, automated system checks, and training sessions for data entry staff.13 A validation study of the BORN birth record system found a high level of agreement with the original patient record for many of the variables used in this study including gestational age, induced delivery and cesarean section, which had 91%, 90%, and 99% agreement with the original patient record respectively.11 The variance for percentage agreement across all variables evaluated was 97.2% (interquartile range, 93.0e99.4%).11
Exposure variables Our primary exposure was ‘any obstetric intervention’ defined as prelabor cesarean section or induced delivery. Our secondary exposures were prelabor cesarean section and induced delivery separately. To avoid overlap between obstetric intervention categories and capture of the event that primarily influenced gestational age at birth, induced deliveries were defined as those with medical or surgical intervention to initiate uterine contractions before the onset of spontaneous labor and included those that subsequently resulted in cesarean section. Prelabor cesarean sections were defined as delivery by cesarean section without prior induction of labor or spontaneous onset of labor. Spontaneous onset of labor was defined as labor that was initiated without intervention, which may have been preceded by spontaneious rupture of membranes. We also explored maternal and obstetric factors known or suspected to be associated with preterm birth. These included maternal characteristics such as maternal age at delivery, socioeconomic status, smoking during pregnancy, parity (nulliparous, primiparous, or multiparous), multifetal pregnancy, previous cesarean section, and number of previous preterm births; maternal health problems including preexisting diabetes (insulin and noninsulin dependent), gestational diabetes, chronic hypertension (hypertension that predates the pregnancy or was diagnosed before the 20th week of gestation), gestational hypertension, infection during pregnancy (composite of any periodontal, urinary tract, vaginal, or cervical infections), and obstetrical complications including
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preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption (premature separation of a normally implanted placenta after the 20th week of gestation and before the fetus is delivered), cord prolapse, chorioamnionitis, breech presentation and small for gestational age (<10 percentile gender specific birthweight for gestational age relative to a Canadian standard reference population for any fetus).12 Socioeconomic status was measured using material and social deprivation from the Deprivation Index, a national index that has been used in many epidemiologic studies and by the Canadian Institute for Health Information as a proxy for socioeconomic status.13,14 The material deprivation component includes: (1) the proportion of persons aged 15 and over who have no high school diploma; (2) the average income of persons aged 15 and over; and (3) the employment to population ratio for persons aged 15 and over. The social deprivation component includes (1) the proportion of people who live alone; (2) the proportion of people separated, divorced, or widowed; and (3) the proportion of single parent families. A factor score is derived from a principal component analysis of these variables at the dissemination area (DA) level, a small, relatively stable geographic unit with a population of 400 to 700 people of relatively homogenous socioeconomic status. Each DA is divided into quintiles based on the corresponding factor scores. DAs in the highest deprivation quintile (Q5) represent the neighborhoods at the highest social disadvantage. We used automated geographic coding based on the Statistics Canada postal code conversion files (PCCFþ v5h) to link the maternal residential postal code in the BORN dataset to the corresponding quintile of deprivation.
Outcome variables For our primary outcome, gestational age at birth was dichotomized as LP (340/7 to 366/7 weeks’ gestation) or term (370/7 to 406/7 weeks’ gestation) based on estimated gestational age at the time of delivery as reported on the birth record.15 Gestational age was estimated from the date of last menstrual period
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TABLE 1
Patient characteristics of the derivation and validation cohorts Derivation cohort (n [ 458,629)
Characteristics, n (%)
Term (37-40 wks) n [ 433,929
Validation cohort (n [ 458,384) Late preterm (34-36 wks) n [ 24,700
Term (37-40 wks) n [ 433,927
Late preterm (34-36 wks) n [ 24,457
Maternal age, y <20
15,080 (3.48)
952 (3.85)
15,292 (3.52)
877 (3.59)
20-24
57,999 (13.37)
3196 (12.94)
57,755 (13.31)
3193 (13.06)
25-34
269,006 (62.00)
14,696 (59.51)
269,456 (62.10)
14,415 (58.95)
35-39
75,819 (17.47)
4664 (18.87)
75,414 (17.38)
4704 (19.23)
>40
15,998 (3.69)
1189 (4.81)
15,980 (3.68)
1264 (5.17)
59,703 (13.97)
3637 (14.96)
59,257 (13.87)
3569 (14.80)
22,459 (5.27)
2874 (11.88)
22,626 (5.31)
2684 (11.19)
Previous cesarean section Previous preterm birth One Multiple
7690 (1.80)
882 (3.65)
7589 (1.78)
872 (3.63)
Parity Nuliparous
188,353 (43.80)
11,682 (47.82)
189,002 (43.94)
11,601 (47.95)
Primiparous
153,461 (35.69)
7674 (31.41)
153,818 (35.76)
7659 (31.66)
Multiparous
88,203 (20.51)
5073 (20.77)
87,302 (20.30)
4934 (20.39)
5236 (1.21)
3082 (12.48)
51,45 (1.19)
3083 (12.61)
45,960 (11.51)
3272 (14.56)
45,876 (11.50)
3294 (14.81)
1 (lowest)
71,913 (17.14)
4037 (16.95)
72,043 (17.17)
4024 (17.09)
2
82,869 (19.75)
4574 (19.21)
82,514 (19.66)
4623 (19.63)
3
82,629 (19.70)
4650 (19.53)
82,129 (19.57)
4541 (19.28)
4
85,986 (20.49)
4865 (20.42)
86,618 (20.64)
4841 (20.54)
5 (highest)
96,145 (22.92)
5685 (23.88)
96,400 (22.97)
5523 (23.45)
1 (lowest)
84,090 (20.04)
4587 (19.26)
83,954 (20.00)
4527 (19.22)
2
83,439 (19.89)
4601 (19.32)
83,299 (19.85)
4552 (19.33)
3
82,408 (19.64)
4712 (19.79)
82,485 (19.65)
4657 (19.77)
4
84,642 (20.17)
4813 (20.20)
84,620 (20.16)
4788 (20.31)
5 (highest)
84,963 (20.25)
5098 (21.41)
85,346 (20.33)
5028 (21.35)
Preexisting diabetes
6090 (1.53)
878 (3.84)
6291 (1.58)
833 (3.67)
Gestational diabetes
18,205 (4.55)
1621 (6.97)
18,165 (4.53)
1643 (7.11)
Chronic hypertension
2677 (0.67)
432 (1.89)
2764 (0.69)
417 (1.84)
Infection during pregnancy
3880 (0.97)
301 (1.29)
3962 (0.99)
289 (1.25)
Multifetal pregnancy Smoking during pregnancy Material deprivation index quintiles
Social deprivation index quintiles
Maternal health problems
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
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TABLE 1
Patient characteristics of the derivation and validation cohorts (continued) Derivation cohort (n [ 458,629) Term (37-40 wks) n [ 433,929
Characteristics, n (%)
Validation cohort (n [ 458,384) Late preterm (34-36 wks) n [ 24,700
Term (37-40 wks) n [ 433,927
Late preterm (34-36 wks) n [ 24,457
Obstetric complications Infection during pregnancy
3880 (0.97)
301 (1.29)
3962 (0.99)
289 (1.25)
122 (0.03)
33 (0.14)
140 (0.03)
38 (0.16)
Preeclampsia
7736 (1.89)
1755 (7.43)
7870 (1.92)
1761 (7.50)
Placental previa
2157 (0.53)
671 (2.85)
2206 (0.54)
667 (2.85)
Uterine bleeding
2967 (0.73)
695 (3.01)
3077 (0.76)
729 (3.17)
Placental abruption
1952 (0.48)
521 (2.21)
2043 (0.50)
563 (2.41)
711 (0.17)
65 (0.28)
665 (0.16)
85 (0.37)
Eclampsia
Cord prolapse Chorioamnionitis
1516 (0.37)
111 (0.48)
1595 (0.39)
Breech presentation
17,431 (4.16)
2514 (10.54)
17,616 (4.21)
2509 (10.60)
104 (0.45)
Small for gestational age (10th percentile)
38,699 (9.03)
2192 (10.15)
38,773 (9.05)
2195 (10.28)
Any obstetric interventiona
164,315 (37.87)
9269 (37.53)
164,913 (38.00)
9316 (38.09)
Inductionb
101,660 (23.53)
4794 (19.49)
102,145 (23.64)
4923 (20.21)
62,655 (14.50)
4475 (18.20)
62,768 (14.53)
4393 (18.04)
Obstetric interventions
Prelabor cesarean section a
c b
c
Includes both induction and cesarean deliveries; Includes inductions ultimately resulting in a cesarean delivery; Excludes cesarean sections that were preceded by induction or spontaneous labor.
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
or dating ultrasound as indicated on the patient record.
Statistical methods For the primary analysis, multivariable generalized estimating equation (GEE) regression was used to test the association between obstetric interventions and late preterm birth (vs term birth) adjusted for maternal and obstetric factors known or suspected to be associated with preterm birth (see above). We chose to use GEE regression to account for clustering within hospitals, which would allow for a more equitable representation of the relationship between risk factors and LP birth than traditional regression techniques. Variables considered for inclusion contained less than 10% missing data and records with missing information on variables included in the models were excluded in the final computation. All variables
specified above were included in the final models regardless of traditional statistical significance as all were believed to be clinically important. Unadjusted and adjusted risk ratio (RR) estimates were computed using a log binomial regression model with hospital site used as the clustering unit for the GEE model to account for clustering of obstetrical interventions within hospitals.16 Colinearity between model parameters was assessed using the variance inflation factor with a cutoff value of 2.0. To explore a dose effect, the association between obstetric interventions and gestational age at birth was explored by week of gestation between 34 and 37 weeks relative to term. For our secondary analysis, the primary analysis was repeated but using induced delivery and prelabor cesarean section as separate exposures. We also conducted an exploratory analysis to examine the independent association
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between maternal and obstetrical factors known or suspected to be associated with preterm birth and LP birth (vs term birth) adjusted for obstetric interventions. To internally validate our model and minimize the risk of spurious associations from multiple hypothesis testing, for both the primary and secondary analyses, all births were randomly assigned to equally sized derivation and validation cohorts.16 The analysis was completed on both cohorts, however, the validation cohort was used to test the associations identified through the derivation cohort. All covariates were included in both derivation and validation models. Statistical analyses were performed using SAS statistical software version 9.2 (SAS Institute, Cary NC) with statistical significance evaluated using 2-sided P values at the 5% level. The study protocol was approved by the Research Ethics
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TABLE 2
Unadjusted and adjusted associations between obstetric interventions and LP gestational age at birth relative to term birth Derivation cohort
Validation cohort a
Variable
uRR
aRR
uRR
aRRa
Any obstetric intervention
0.96 (0.85e1.09)
0.65 (0.57e0.74)
0.97 (0.85e1.11)
0.65 (0.57e0.73)
Induction
0.76 (0.65e0.89)
0.71 (0.61e0.82)
0.79 (0.69e0.90)
0.71 (0.63e0.81)
Prelabor cesarean section
1.30 (1.21e1.40)
0.66 (0.59e0.74)
1.28 (1.19e1.39)
0.66 (0.59e0.73)
aRR, adjusted risk ratio; uRR, unadjusted risk ratio. a
Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
Boards of the Children’s Hospital of Eastern Ontario, the St. Michael’s Hospital and the Mount Sinai Hospital in Toronto.
R ESULTS From April 2005 through March 2012 there were 925,293 live births in Ontario hospitals, 6.5% of births had incomplete data capture. After excluding births with a birthweight <500 g and those with incomplete data, there were 917,013 live births between 34 to 40 completed weeks of gestation, of which 49,157 (5.4%) were identified as LP. Obstetricians provided care to 79%, family physicians to 27%, midwives to 7% and nurse practitioners to 2% of women (15% of women had multiple care providers). Births occurred in 106 different hospital sites; 23% Level 3, 65% Level 2, and 12% Level 1 centers. The derivation and validation cohorts consisted of 458,629 and 458,384 births
respectively. Overall, the patient characteristics were similar between the 2 cohorts (Table 1). The most common maternal age range was 25e34 years and most mothers had not had a previous preterm birth. In both cohorts, any obstetric intervention’ occurred in 38% of births, 21% were induced deliveries and 17% were prelabor cesarean sections. Overall, variable colinearity was low (variance inflation factor between 1.00-1.9). In the univariable analysis of the derivation cohort, ‘any obstetric intervention’ was not significantly associated with LP birth (RR, 0.96; 95% confidence interval [CI], 0.85e1.09). Prelabor cesarean section was positively associated with LP birth (RR, 1.30; 95% CI, 1.21e1.40) and induction was negatively associated with LP birth (RR, 0.76; 95% CI, 0.65e0.89). For our primary analysis, adjustment for maternal and obstetric factors known
or suspected to be associated with preterm birth identified that ‘any obstetric intervention’ was associated with a lower likelihood of LP birth relative to term birth in the derivation cohort (RR, 0.65; 95% CI, 0.57e0.74). For our secondary analysis, adjusted risk ratio estimates for induction and prelabor cesarean section were also negatively associated with LP birth relative to term birth (RR, 0.71; 95% CI, 0.61e0.82 and RR, 0.66; 95% CI, 0.59e0.74 respectively) (Table 2). Exploring the adjusted association between obstetric interventions by week of gestational age at birth in the derivation cohort revealed that ‘any obstetric interventions’, induction and prelabor cesarean section were negatively associated with LP birth through the 36th week of gestation with cesarean section reaching statistical nonsignificance at 37 weeks’ gestation (Table 3).
TABLE 3
Associations between obstetrical interventions by week of gestation relative to term birth in the derivation cohort 34 wks a
35 wks
36 wks
a
a
37 wks
Variable
aRR
aRR
aRR
aRRa,b
Any obstetric intervention
0.49 (0.39e0.62)
0.57 (0.49e0.68)
0.65 (0.57e0.74)
0.92 (0.83e1.03)
Induction
0.43 (0.32e0.58)
0.61 (0.51e0.74)
0.74 (0.65e0.85)
0.81 (0.75e0.88)
Prelabor cesarean section
0.73 (0.58e0.93)
0.63 (0.53e0.76)
0.59 (0.51e0.68)
0.79 (0.72e0.87)
aRR, adjusted risk ratio. a
Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age; b aRR for the 37th week gestation calculated by considering term gestation to be 380⁄7 to 406⁄7 weeks.
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
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TABLE 4
Associations between maternal and fetal factors and LP gestational age at birth Derivation cohort
Validation cohort
uRR
aRR
uRR
aRRa
<20
1.18 (1.08e1.28)
1.06 (0.98e1.16)
1.09 (0.99e1.19)
1.00 (0.91e1.10)
20-24
1.02 (0.97e1.08)
1.02 (0.97e1.07)
1.06 (1.01e1.10)
1.06 (1.01e1.11)
25-34
Ref
Ref
Ref
Ref
35-39
1.11 (1.05e1.17)
1.06 (1.01e1.12)
1.14 (1.08e1.20)
1.10 (1.05e1.15)
>40
1.34 (1.23e1.46)
1.15 (1.06e1.25)
1.44 (1.33e1.57)
1.25 (1.16e1.34)
1 (lowest)
Ref
Ref
Ref
Ref
2
1.05 (0.97e1.14)
1.08 (1.03e1.13)
1.09 (1.03e1.16)
1.06 (1.00e1.11)
3
1.09 (0.98e1.20)
1.08 (1.01e1.16)
1.09 (1.02e1.17)
1.04 (0.99e1.10)
4
1.10 (1.00e1.21)
1.05 (0.99e1.12)
1.11 (1.04e1.19)
1.05 (1.00e1.10)
5 (highest)
1.15 (1.04e1.27)
1.10 (1.03e1.18)
1.14 (1.07e1.22)
1.07 (1.01e1.13)
Ref
Ref
Ref
Ref
Maternal characteristics
a
Maternal age, y
Material deprivation index quintiles
Social deprivation index quintiles 1 (lowest) 2
1.02 (0.97e1.07)
1.02 (0.98e1.07)
1.01 (0.96e1.06)
1.03 (0.98e1.09)
3
1.04 (0.99e1.09)
1.05 (1.00e1.10)
1.03 (0.97e1.09)
1.05 (0.99e1.11)
4
1.02 (0.95e1.10)
1.05 (0.99e1.11)
1.02 (0.96e1.08)
1.04 (0.99e1.10)
5 (highest)
1.05 (0.97e1.14)
1.09 (1.02e1.16)
1.03 (0.96e1.11)
1.07 (1.01e1.12)
Multifetal pregnancy
8.70 (7.99e9.46)
6.28 (5.85e6.74)
8.89 (8.19e9.64)
6.18 (5.74e6.64)
Smoking during pregnancy
1.35 (1.26e1.45)
1.28 (1.21e1.36)
1.41 (1.33e1.49)
1.34 (1.28e1.41)
Previous cesarean section
1.06 (1.01e1.12)
1.28 (1.16e1.40)
1.05 (0.99e1.12)
1.28 (1.18e1.39)
One
2.71 (1.88e3.89)
2.93 (2.27e3.78)
2.52 (1.78e3.57)
2.70 (2.14e3.41)
Multiple
2.58 (1.63e4.10)
2.77 (1.85e4.15)
2.60 (1.65e4.09)
2.78 (1.80e4.32)
Nuliparous
Ref
Ref
Ref
Ref
Primiparous
0.80 (0.76e0.84)
0.68 (0.63e0.73)
0.81 (0.77e0.85)
0.70 (0.66e0.74)
Multiparous
0.94 (0.89e1.00)
0.68 (0.62e0.74)
0.94 (0.88e1.00)
0.68 (0.63e0.74)
Previous preterm birth
Parity
Maternal health problems Preexisting diabetes
2.55 (2.34e2.79)
2.04 (1.81e2.30)
2.37 (2.14e2.64)
1.92 (1.74e2.12)
Gestational diabetes
1.60 (1.50e1.71)
1.32 (1.22e1.43)
1.65 (1.52e1.79)
1.39 (1.28e1.51)
Chronic hypertension
2.72 (2.43e3.05)
1.52 (1.30e1.78)
2.56 (2.32e2.83)
1.50 (1.33e1.69)
Infection during pregnancy
1.30 (1.07e1.60)
1.21 (1.03e1.42)
1.21 (0.95e1.55)
1.19 (1.00e1.42)
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
For our exploratory analysis, most of the hypothesized risk factors for preterm birth were independently associated with LP gestational age at birth in
the derivation cohort (Table 4). The strongest associated risk factor for LP gestational age at birth was multifetal pregnancy (RR, 6.28; 95% CI, 5.85e6.74)
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(continued)
followed by placenta previa (RR, 4.35; 95% CI, 3.88e4.89), preeclampsia (RR, 3.32; 95% CI, 3.05e3.60) and previous preterm birth (RR, 2.93; 95% CI,
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TABLE 4
Associations between maternal and fetal factors and LP gestational age at birth (continued) Derivation cohort Maternal characteristics
uRR
Validation cohort a
aRR
uRR
aRRa
Obstetric complications Eclampsia
4.44 (3.33e5.93)
2.23 (1.58e3.16)
4.46 (2.95e6.73)
2.16 (1.52e3.08)
Preeclampsia
3.91 (3.58e4.27)
3.32 (3.05e3.60)
3.88 (3.58e4.21)
3.15 (2.86e3.47)
Placental previa
5.01 (4.53e5.53)
4.35 (3.88e4.89)
4.93 (4.29e5.66)
4.42 (3.86e5.06)
Uterine bleeding
4.01 (3.44e4.68)
1.83 (1.59e2.11)
4.05 (3.47e4.71)
1.85 (1.63e2.10)
Placental abruption
4.34 (3.67e5.14)
2.05 (1.68e2.50)
4.47 (3.79e5.27)
2.33 (2.00e2.72)
Cord prolapse
1.56 (1.07e2.27)
0.81 (0.52e1.28)
2.22 (1.66e2.97)
1.60 (1.21e2.12)
Chorioamnionitis
1.22 (0.88e1.69)
1.12 (0.84e1.49)
1.04 (0.69e1.57)
1.09 (0.81e1.46)
Breech presentation
2.69 (2.54e2.84)
2.08 (1.96e2.22)
2.68 (2.53e2.84)
2.06 (1.93e2.21)
Small for gestational age (10th percentile)
1.14 (1.03e1.26)
1.04 (0.95e1.13)
1.16 (1.06e1.26)
1.05 (0.98e1.13)
aRR, adjusted risk ratio; LP, late preterm; ref, reference; uRR, unadjusted risk ratio. a
Adjusted for induction, smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
2.27e3.78). Several potentially modifiable risk factors were also associated with LP gestational age at birth including smoking during pregnancy (RR, 1.28; 95% CI, 1.21e1.36), previous cesarean section (RR, 1.28; 95% CI, 1.16e1.40) and high material (RR, 1.1; 95% CI, 1.03e1.18) and social (RR, 1.09; 95% CI, 1.02e1.16) deprivation indices. Repeating the primary and secondary analyses using the validation cohort led to similar findings (Tables 2-4).
C OMMENT We have used population based data from the largest province in Canada, to examine the magnitude of the association between obstetrical interventions and LP birth taking into account numerous known or suspected maternal and obstetrical risk factors for preterm birth. We have identified that induction and prelabor cesarean section were associated with a lower likelihood of LP birth relative to term birth for pregnancies with similar maternal and fetal risk. Further, this trend persisted through each LP gestational week up to 37 weeks. We have also identified several potentially modifiable risk factors which were associated
with LP birth, independent of obstetrical interventions, including previous cesarean section, smoking during pregnancy and high social and material deprivation. There has been concern that the escalation in LP birth over the past 20 years may be related to obstetric interventions and iatrogenic preterm birth.17 In Canada, the overall rate of cesarean delivery increased from 21.9% in 2001/2002 to 27.8% in 2009/2010.18 A recent multicountry analysis that aimed to understand the main drivers for the increase in the preterm birth rate over time identified that cesarean section and labor induction together accounted for approximately 20% of the change in LP birth between 1989 and 2004.19 However, maternal and fetal health problems are also increasing and expedited delivery through obstetric intervention in the setting of maternal or fetal compromise is generally accepted practice to avoid potentially disastrous maternal or neonatal outcomes.20 Overall rates of stillbirth and perinatal death in the US have decreased in parallel to the increase in LP births prompting some to argue that obstetric intervention may be preventing stillbirth and perinatal
death.21,22 Our findings add to this literature by suggesting that obstetrical care providers may be preferentially avoiding interventions to bring about LP birth in the setting of equivalent maternal and obstetric risk. We speculate that increased awareness among obstetric care providers about the harms of unnecessary LP birth may be a contributing factor. Another contributing factor may be elective cesarean section and induction which obstetric care providers may be more liberal with in the term than in the late preterm period. We have also identified several potentially modifiable factors which were independently associated with LP birth and may be useful targets for interventions to reduce LP birth. Consistent with other studies, previous cesarean section was associated with a 28% increased likelihood of LP birth suggesting that efforts to minimize term and preterm cesarean sections may decrease risk of LP birth in subsequent pregnancies.23-25 Smoking during pregnancy was associated with a 30% increased likelihood of LP birth. Strengths of our study include the clinical richness of the BORN
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Information System, which allowed for more thorough adjustment for maternal and obstetric risk factors. The magnitude of the change of the association between obstetric interventions and LP birth before and after adjustment for maternal and obstetric risk factors underscores the influence that such risk factors likely have on care provider decisions around obstetric interventions. Population based data also allowed us to use a validation cohort to verify our findings and minimize risk of spurious findings from multiple hypothesis testing.26 GEE modeling allowed us to account for clustering of obstetric interventions, which have been documented to vary considerably between hospitals.27 Our study has several limitations. Although a validation exercise has examined our primary outcome and primary exposure variables, several of the variables used in our analysis have not been validated raising the potential for coding error or misclassification.11 Induction and prelabor cesarean section were coded as mutually exclusive categories to capture the obstetric intervention that initiated the birth process. This resulted in a lower than expected frequency of cesarean sections since those that were proceeded by spontaneous labor or induction of labor were not included in the prelabor cesarean variable. It is also possible that our findings may have been influenced by incomplete adjustment. However, when we repeated our primary analysis using only the 32% of pregnancies with no identified risk factor for LP birth, the effect sizes were similar to our primary analysis (data not shown). We also considered that our finding of a negative association between obstetric interventions and LP birth may be reflective of increased risk of obstetrical interventions past 40 weeks gestation and our definition of “term” pregnancy included women up to 40 6/7 weeks’ gestation. However, a sensitivity analysis excluding births over 40 weeks’ gestation resulted in similar findings to our primary analysis (data not shown). Our findings suggest that over the past 7 years, the likelihood of birth associated
www.AJOG.org with obstetric interventions in Ontario was lower in the LP period than the term period once maternal and obstetric risk factors were taken into account. Obstetric care providers may be preferentially not intervening to bring about birth before term in the setting of equivalent maternal and obstetric risk. Although ongoing vigilance to avoid unnecessary late preterm obstetric interventions is warranted, strategies focusing on modifiable risk factors for LP birth may be helpful including minimizing unnecessary prelabor cesarean sections, smoking cessation, and reducing material and social deprivation. ACKNOWLEDGMENTS Support for this study was provided by both the Physician Services Incorporated Foundation and the St. Michael’s Hospital AFP Innovation Fund. Funding agencies had no role in the design, collection, analysis or interpretation of results in this study. We would also like to acknowledge the following individuals for their technical, administrative, and statistical support of this study: Sharmilaa Kandasamy, Research Coordinator II, Employed and Funded by the Department of Paediatrics, St. Michael’s Hospital Julie DeGroot, Clinical Research Project Manager, Employed and Funded by the Pediatric Outcomes Research Team, Hospital for Sick Children Rosane Nisenbaum, Senior Biostatistician, Employed and Funded by the Applied Health Research Centre, St. Michael’s Hospital
REFERENCES 1. Kramer MS, Demissie K, Yang H, Platt RW, Sauve R, Liston R. The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. JAMA 2000;284: 843-9. 2. Davidoff MJ, Dias T, Damus K, et al. Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to 2002. Semin Perinatol 2006;30: 8-15. 3. Tomashek KM, Shapiro-Mendoza CK, Davidoff MJ, Petrini JR. Differences in mortality between late-preterm and term singleton infants in the United States, 1995-2002. J Pediatr 2007;151:450-6, 456, e451. 4. Loftin RW, Habli M, Snyder CC, Cormier CM, Lewis DF, Defranco EA. Late preterm birth. Rev Obstet Gynecol 2010;3:10-9. 5. Ramachandrappa A, Jain L. Health issues of the late preterm infant. Pediatr Clin North Am 2009;56:565-77, Table of Contents.
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6. Huddy CL, Johnson A, Hope PL. Educational and behavioural problems in babies of 32-35 weeks gestation. Arch Dis Child Fetal Neonatal Ed 2001;85:F23-8. 7. Santos IS, Matijasevich A, Domingues MR, Barros AJ, Victora CG, Barros FC. Late preterm birth is a risk factor for growth faltering in early childhood: a cohort study. BMC Pediatr 2009;9:71. 8. Mohan SS, Jain L. Late preterm birth: preventable prematurity? Clin Perinatol 2011;38: 547-55. 9. Martin JA, Kirmeyer S, Osterman M, Shepherd RA. Born a bit too early: recent trends in late preterm births. NCHS Data Brief 2009: 1-8. 10. Voelker R. US preterm births: “D” is for dismal. JAMA 2010;303:116-7. 11. Dunn S, Bottomley J, Ali A, Walker M. 2008 Niday Perinatal Database quality audit: report of a quality assurance project. Chronic Dis Inj Can 2011;32:32-42. 12. Kramer MS, Platt RW, Wen SW, et al. A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics 2001;108:E35. 13. Canadian Institute for Health Information. Reducing gaps in health: a focus on socioeconomic status in urban Canada. Ottawa, Ontario: CIHI; 2008. Available at: https://secure.cihi. ca/free_products/Reducing_Gaps_in_Health_ Report_EN_081009.pdf. Accessed April 10, 2013. 14. Pampalon R, Raymond G. A deprivation index for health and welfare planning in Quebec. Chronic Dis Can 2000;21:104-13. 15. Engle WA. A recommendation for the definition of “late preterm” (near-term) and the birth weight-gestational age classification system. Semin Perinatol 2006;30:2-7. 16. Austin PC, Mamdani MM, Juurlink DN, Hux JE. Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health. J Clin Epidemiol 2006;59:964-9. 17. Joseph KS, D’Alton M. Theoretical and empirical justification for current rates of iatrogenic delivery at late preterm gestation. Paediatr Perinat Epidemiol 2013;27:2-6. 18. Public Health Agency of Canada. Perinatal Health Indicators for Canada, 2011. Available at: http://www.phac-aspc.gc.ca/rhsssg/phi-isp-2011-eng.php. Accessed April 1, 2014. 19. Chang HH, Larson J, Blencowe H, et al. Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index. Lancet 2013;381:223-34. 20. Fuchs K, Gyamfi C. The influence of obstetric practices on late prematurity. Clin Perinatol 2008;35:343-60, vi. 21. Ananth CV, Joseph KS, Kinzler WL. The influence of obstetric intervention on trends in twin stillbirths: United States, 1989-99. J Matern Fetal Neonatal Med 2004;15: 380-7.
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www.AJOG.org 22. Kramer MS, Zhang X, Iams J. The rise in late preterm obstetric intervention: has it done more good than harm? Paediatr Perinat Epidemiol 2013;27:7-10. 23. Di Renzo GC, Giardina I, Rosati A, Clerici G, Torricelli M, Petraglia F. Maternal risk factors for preterm birth: a country-based population analysis. Eur J Obstet Gynecol Reprod Biol 2011;159:342-6.
24. Taylor LK, Simpson JM, Roberts CL, Olive EC, Henderson-Smart DJ. Risk of complications in a second pregnancy following caesarean section in the first pregnancy: a population-based study. Med J Aust 2005;183: 515-9. 25. Kennare R, Tucker G, Heard A, Chan A. Risks of adverse outcomes in the next birth after
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a first cesarean delivery. Obstet Gynecol 2007;109(Pt 1):270-6. 26. Picard RR, Berk KN. Data splitting. Am Stat 1990;44:140-7. 27. Kelly S, Sprague A, Fell DB, et al. Examining caesarean section rates in Canada using the robson classification system. J Obstet Gynaecol Can 2013;35:206-14.
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OBSTETRICS
The association between obstetrical interventions and late preterm birth Kate L. Bassil, PhD; Abdool S. Yasseen III, MSc; Mark Walker, MD; Michael D. Sgro, MD; Prakesh S. Shah, MD; Graeme N. Smith, MD, PhD; Douglas M. Campbell, MD; Muhammad Mamdani, PharmD; Ann E. Sprague, PhD; Shoo K. Lee, MD; Jonathon L. Maguire, MD OBJECTIVE: There is concern that obstetric interventions (prelabor cesarean section and induced delivery) are drivers of late preterm (LP) birth. Our objective was to evaluate the independent association between obstetric interventions and LP birth and explore associated independent maternal and fetal risk factors for LP birth. STUDY DESIGN: In this population-based cross-sectional study, the
BORN Information System was used to identify all infants born between 34 and 40 completed weeks of gestation between 2005 and 2012 in Ontario, Canada. The association between obstetric interventions (preterm cesarean section and induced delivery) and LP birth (34 to 36 completed weeks’ gestation vs 37 to 40 completed weeks’ gestation) was assessed using generalized estimating equation regression. RESULTS: Of 917,013 births between 34 and 40 weeks, 49,157 were
LP (5.4%). In the adjusted analysis, “any obstetric intervention” (risk
ratio [RR], 0.65; 95% confidence interval [CI], 0.57e0.74), induction (RR, 0.71; 95% CI, 0.61e0.82) and prelabor cesarean section (RR, 0.66; 95% CI, 0.59e0.74) were all associated with a lower likelihood of LP vs term birth. Several independent potentially modifiable risk factors for LP birth were identified including previous cesarean section (RR, 1.28; 95% CI, 1.16e1.40), smoking during pregnancy (RR, 1.28; 95% CI, 1.21e1.36) and high material (RR, 1.1; 95% CI, 1.03e1.18) and social (RR, 1.09; 95% CI, 1.02e1.16) deprivation indices. CONCLUSION: After accounting for differences in maternal and fetal risk,
LP births had a 35% lower likelihood of obstetric interventions than term births. Obstetric care providers may be preferentially avoiding induction and prelabor cesarean section between 34 and 37 weeks’ gestation. Key words: cesarean delivery, late preterm, maternal health, obstetric intervention, risk factors
Cite this article as: Bassil KL, Yasseen III AS, Walker M, et al. The association between obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014;210:x-ex-x-ex.
P
reterm birth is the leading cause of infant morbidity and mortality and has been described as the most important perinatal challenge facing industrialized countries.1 Among preterm infants (<37 weeks’ of gestation), “late preterm” (LP) infants (born between 340 and 366 weeks of gestation) account for the largest proportion (74%) and are the fastest growing subgroup.1,2 Children born LP are at greater risk than term
infants (37 weeks) for numerous short and long-term adverse outcomes.3-7 Two groups of LP birth have been defined by their etiology: spontaneous LP births (ie, premature labor with intact membranes or preterm prelabor rupture of membranes), and LP births because of obstetric intervention (ie, induction of labor or cesarean section).8 There
is concern that obstetric interventions may be driving the increase in LP birth in recent years and are responsible for a substantial proportion of LP births.9,10 Understanding the independent contribution of obstetric interventions in the context of maternal and fetal risk factors for LP birth has been challenging largely owing to limitations in population based data on maternal and fetal risk factors for LP birth.
From the Maternal-Infant Care Research Institute (Drs Bassil, Lee, and Shah) and the Department of Pediatrics (Drs Shah and Lee), Mount Sinai Hospital; Li Ka Shing Knowledge Institute (Drs Sgro, Campbell, Mamdani, and Maguire) and the Department of Pediatrics (Drs Sgro, Campbell, and Maguire), St. Michael’s Hospital; Department of Pediatrics, Faculty of Medicine (Drs Sgro, Shah, Lee, and Maguire), and Leslie Dan Faculty of Pharmacy (Dr Mamdani), University of Toronto, Toronto; BORN Ontario (Better Outcomes Registry & Network) (Mr Yasseen and Drs Walker and Sprague), and Department of Obstetrics and Gynecology (Mr Yasseen and Dr Walker), Ottawa Hospital Research Institute, and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa; and Department of Obstetrics and Gynecology (Dr Smith), Faculty of Medicine, Queen’s University, Kingston, ON, Canada. Received Nov. 6, 2013; revised Jan. 10, 2014; accepted Feb. 24, 2014. The authors report no conflict of interest. Financial support for this project was supplied by Physician’s Services Incorporated Foundation, the St. Michael’s Hospital Academic Funding Plan Innovation Fund and the St. Michael’s Foundation. Reprints: Jonathon Maguire, Department of Pediatrics, St. Michael’s Hospital, 30 Bond St., 15CC-014, Toronto ON M5B 1W8. jonathon.maguire@ utoronto.ca. 0002-9378/free ª 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2014.02.023
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The objective of this study was to evaluate the magnitude and direction of the association between obstetric interventions (induced delivery and cesarean section) and LP birth (relative to term birth) in the context of known risk factors for preterm birth. We also aimed to explore the magnitude of the associations between maternal and fetal risk factors for LP birth, independent of obstetric interventions, which could be targets for interventions to prevent LP birth.
M ETHODS This was a population-based cohort study of pregnant women in Ontario, Canada, between April 1, 2005, and March 31, 2012.
Study population All women who gave birth in a hospital to a live infant >500 g birthweight with a gestational age between 340/7 and 406/7 weeks in Ontario, Canada, between 2005 and 2012 were eligible for inclusion in this study. Women who gave birth between 410/7 and 416/7 weeks’ gestation were excluded to avoid capturing an increased risk of obstetric interventions in the 41st week of gestation. Sources of data Data were obtained from the BORN Information System (BIS), which is a provincial, internet-based maternal newborn surveillance system managed by the Better Outcomes Registry & Network (BORN Ontario). Maternal, fetal, and obstetric data were extracted for the study time period, April 1, 2004, to March 31, 2012. In a birth number validation exercise between the CIHI Discharge Abstract Database and the BIS, the BORN system captured 82% of hospital births in the 2004-2005 fiscal year and increased yearly until 100% of hospital births from 106 sites were captured by 2010-11. The BIS includes information on maternal demographic characteristics and health behaviors, preexisting maternal health problems, obstetric complications, intrapartum interventions, and birth outcomes. Various quality assurance mechanisms were used to ensure high data quality and consistency including data entry operating
www.AJOG.org manuals, automated system checks, and training sessions for data entry staff.13 A validation study of the BORN birth record system found a high level of agreement with the original patient record for many of the variables used in this study including gestational age, induced delivery and cesarean section, which had 91%, 90%, and 99% agreement with the original patient record respectively.11 The variance for percentage agreement across all variables evaluated was 97.2% (interquartile range, 93.0e99.4%).11
Exposure variables Our primary exposure was ‘any obstetric intervention’ defined as prelabor cesarean section or induced delivery. Our secondary exposures were prelabor cesarean section and induced delivery separately. To avoid overlap between obstetric intervention categories and capture of the event that primarily influenced gestational age at birth, induced deliveries were defined as those with medical or surgical intervention to initiate uterine contractions before the onset of spontaneous labor and included those that subsequently resulted in cesarean section. Prelabor cesarean sections were defined as delivery by cesarean section without prior induction of labor or spontaneous onset of labor. Spontaneous onset of labor was defined as labor that was initiated without intervention, which may have been preceded by spontaneious rupture of membranes. We also explored maternal and obstetric factors known or suspected to be associated with preterm birth. These included maternal characteristics such as maternal age at delivery, socioeconomic status, smoking during pregnancy, parity (nulliparous, primiparous, or multiparous), multifetal pregnancy, previous cesarean section, and number of previous preterm births; maternal health problems including preexisting diabetes (insulin and noninsulin dependent), gestational diabetes, chronic hypertension (hypertension that predates the pregnancy or was diagnosed before the 20th week of gestation), gestational hypertension, infection during pregnancy (composite of any periodontal, urinary tract, vaginal, or cervical infections), and obstetrical complications including
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preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption (premature separation of a normally implanted placenta after the 20th week of gestation and before the fetus is delivered), cord prolapse, chorioamnionitis, breech presentation and small for gestational age (<10 percentile gender specific birthweight for gestational age relative to a Canadian standard reference population for any fetus).12 Socioeconomic status was measured using material and social deprivation from the Deprivation Index, a national index that has been used in many epidemiologic studies and by the Canadian Institute for Health Information as a proxy for socioeconomic status.13,14 The material deprivation component includes: (1) the proportion of persons aged 15 and over who have no high school diploma; (2) the average income of persons aged 15 and over; and (3) the employment to population ratio for persons aged 15 and over. The social deprivation component includes (1) the proportion of people who live alone; (2) the proportion of people separated, divorced, or widowed; and (3) the proportion of single parent families. A factor score is derived from a principal component analysis of these variables at the dissemination area (DA) level, a small, relatively stable geographic unit with a population of 400 to 700 people of relatively homogenous socioeconomic status. Each DA is divided into quintiles based on the corresponding factor scores. DAs in the highest deprivation quintile (Q5) represent the neighborhoods at the highest social disadvantage. We used automated geographic coding based on the Statistics Canada postal code conversion files (PCCFþ v5h) to link the maternal residential postal code in the BORN dataset to the corresponding quintile of deprivation.
Outcome variables For our primary outcome, gestational age at birth was dichotomized as LP (340/7 to 366/7 weeks’ gestation) or term (370/7 to 406/7 weeks’ gestation) based on estimated gestational age at the time of delivery as reported on the birth record.15 Gestational age was estimated from the date of last menstrual period
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TABLE 1
Patient characteristics of the derivation and validation cohorts Derivation cohort (n [ 458,629)
Characteristics, n (%)
Term (37-40 wks) n [ 433,929
Validation cohort (n [ 458,384) Late preterm (34-36 wks) n [ 24,700
Term (37-40 wks) n [ 433,927
Late preterm (34-36 wks) n [ 24,457
Maternal age, y <20
15,080 (3.48)
952 (3.85)
15,292 (3.52)
877 (3.59)
20-24
57,999 (13.37)
3196 (12.94)
57,755 (13.31)
3193 (13.06)
25-34
269,006 (62.00)
14,696 (59.51)
269,456 (62.10)
14,415 (58.95)
35-39
75,819 (17.47)
4664 (18.87)
75,414 (17.38)
4704 (19.23)
>40
15,998 (3.69)
1189 (4.81)
15,980 (3.68)
1264 (5.17)
59,703 (13.97)
3637 (14.96)
59,257 (13.87)
3569 (14.80)
22,459 (5.27)
2874 (11.88)
22,626 (5.31)
2684 (11.19)
Previous cesarean section Previous preterm birth One Multiple
7690 (1.80)
882 (3.65)
7589 (1.78)
872 (3.63)
Parity Nuliparous
188,353 (43.80)
11,682 (47.82)
189,002 (43.94)
11,601 (47.95)
Primiparous
153,461 (35.69)
7674 (31.41)
153,818 (35.76)
7659 (31.66)
Multiparous
88,203 (20.51)
5073 (20.77)
87,302 (20.30)
4934 (20.39)
5236 (1.21)
3082 (12.48)
51,45 (1.19)
3083 (12.61)
45,960 (11.51)
3272 (14.56)
45,876 (11.50)
3294 (14.81)
1 (lowest)
71,913 (17.14)
4037 (16.95)
72,043 (17.17)
4024 (17.09)
2
82,869 (19.75)
4574 (19.21)
82,514 (19.66)
4623 (19.63)
3
82,629 (19.70)
4650 (19.53)
82,129 (19.57)
4541 (19.28)
4
85,986 (20.49)
4865 (20.42)
86,618 (20.64)
4841 (20.54)
5 (highest)
96,145 (22.92)
5685 (23.88)
96,400 (22.97)
5523 (23.45)
1 (lowest)
84,090 (20.04)
4587 (19.26)
83,954 (20.00)
4527 (19.22)
2
83,439 (19.89)
4601 (19.32)
83,299 (19.85)
4552 (19.33)
3
82,408 (19.64)
4712 (19.79)
82,485 (19.65)
4657 (19.77)
4
84,642 (20.17)
4813 (20.20)
84,620 (20.16)
4788 (20.31)
5 (highest)
84,963 (20.25)
5098 (21.41)
85,346 (20.33)
5028 (21.35)
Preexisting diabetes
6090 (1.53)
878 (3.84)
6291 (1.58)
833 (3.67)
Gestational diabetes
18,205 (4.55)
1621 (6.97)
18,165 (4.53)
1643 (7.11)
Chronic hypertension
2677 (0.67)
432 (1.89)
2764 (0.69)
417 (1.84)
Infection during pregnancy
3880 (0.97)
301 (1.29)
3962 (0.99)
289 (1.25)
Multifetal pregnancy Smoking during pregnancy Material deprivation index quintiles
Social deprivation index quintiles
Maternal health problems
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
(continued)
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TABLE 1
Patient characteristics of the derivation and validation cohorts (continued) Derivation cohort (n [ 458,629) Term (37-40 wks) n [ 433,929
Characteristics, n (%)
Validation cohort (n [ 458,384) Late preterm (34-36 wks) n [ 24,700
Term (37-40 wks) n [ 433,927
Late preterm (34-36 wks) n [ 24,457
Obstetric complications Infection during pregnancy
3880 (0.97)
301 (1.29)
3962 (0.99)
289 (1.25)
122 (0.03)
33 (0.14)
140 (0.03)
38 (0.16)
Preeclampsia
7736 (1.89)
1755 (7.43)
7870 (1.92)
1761 (7.50)
Placental previa
2157 (0.53)
671 (2.85)
2206 (0.54)
667 (2.85)
Uterine bleeding
2967 (0.73)
695 (3.01)
3077 (0.76)
729 (3.17)
Placental abruption
1952 (0.48)
521 (2.21)
2043 (0.50)
563 (2.41)
711 (0.17)
65 (0.28)
665 (0.16)
85 (0.37)
Eclampsia
Cord prolapse Chorioamnionitis
1516 (0.37)
111 (0.48)
1595 (0.39)
Breech presentation
17,431 (4.16)
2514 (10.54)
17,616 (4.21)
2509 (10.60)
104 (0.45)
Small for gestational age (10th percentile)
38,699 (9.03)
2192 (10.15)
38,773 (9.05)
2195 (10.28)
Any obstetric interventiona
164,315 (37.87)
9269 (37.53)
164,913 (38.00)
9316 (38.09)
Inductionb
101,660 (23.53)
4794 (19.49)
102,145 (23.64)
4923 (20.21)
62,655 (14.50)
4475 (18.20)
62,768 (14.53)
4393 (18.04)
Obstetric interventions
Prelabor cesarean section a
c b
c
Includes both induction and cesarean deliveries; Includes inductions ultimately resulting in a cesarean delivery; Excludes cesarean sections that were preceded by induction or spontaneous labor.
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
or dating ultrasound as indicated on the patient record.
Statistical methods For the primary analysis, multivariable generalized estimating equation (GEE) regression was used to test the association between obstetric interventions and late preterm birth (vs term birth) adjusted for maternal and obstetric factors known or suspected to be associated with preterm birth (see above). We chose to use GEE regression to account for clustering within hospitals, which would allow for a more equitable representation of the relationship between risk factors and LP birth than traditional regression techniques. Variables considered for inclusion contained less than 10% missing data and records with missing information on variables included in the models were excluded in the final computation. All variables
specified above were included in the final models regardless of traditional statistical significance as all were believed to be clinically important. Unadjusted and adjusted risk ratio (RR) estimates were computed using a log binomial regression model with hospital site used as the clustering unit for the GEE model to account for clustering of obstetrical interventions within hospitals.16 Colinearity between model parameters was assessed using the variance inflation factor with a cutoff value of 2.0. To explore a dose effect, the association between obstetric interventions and gestational age at birth was explored by week of gestation between 34 and 37 weeks relative to term. For our secondary analysis, the primary analysis was repeated but using induced delivery and prelabor cesarean section as separate exposures. We also conducted an exploratory analysis to examine the independent association
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between maternal and obstetrical factors known or suspected to be associated with preterm birth and LP birth (vs term birth) adjusted for obstetric interventions. To internally validate our model and minimize the risk of spurious associations from multiple hypothesis testing, for both the primary and secondary analyses, all births were randomly assigned to equally sized derivation and validation cohorts.16 The analysis was completed on both cohorts, however, the validation cohort was used to test the associations identified through the derivation cohort. All covariates were included in both derivation and validation models. Statistical analyses were performed using SAS statistical software version 9.2 (SAS Institute, Cary NC) with statistical significance evaluated using 2-sided P values at the 5% level. The study protocol was approved by the Research Ethics
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TABLE 2
Unadjusted and adjusted associations between obstetric interventions and LP gestational age at birth relative to term birth Derivation cohort
Validation cohort a
Variable
uRR
aRR
uRR
aRRa
Any obstetric intervention
0.96 (0.85e1.09)
0.65 (0.57e0.74)
0.97 (0.85e1.11)
0.65 (0.57e0.73)
Induction
0.76 (0.65e0.89)
0.71 (0.61e0.82)
0.79 (0.69e0.90)
0.71 (0.63e0.81)
Prelabor cesarean section
1.30 (1.21e1.40)
0.66 (0.59e0.74)
1.28 (1.19e1.39)
0.66 (0.59e0.73)
aRR, adjusted risk ratio; uRR, unadjusted risk ratio. a
Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
Boards of the Children’s Hospital of Eastern Ontario, the St. Michael’s Hospital and the Mount Sinai Hospital in Toronto.
R ESULTS From April 2005 through March 2012 there were 925,293 live births in Ontario hospitals, 6.5% of births had incomplete data capture. After excluding births with a birthweight <500 g and those with incomplete data, there were 917,013 live births between 34 to 40 completed weeks of gestation, of which 49,157 (5.4%) were identified as LP. Obstetricians provided care to 79%, family physicians to 27%, midwives to 7% and nurse practitioners to 2% of women (15% of women had multiple care providers). Births occurred in 106 different hospital sites; 23% Level 3, 65% Level 2, and 12% Level 1 centers. The derivation and validation cohorts consisted of 458,629 and 458,384 births
respectively. Overall, the patient characteristics were similar between the 2 cohorts (Table 1). The most common maternal age range was 25e34 years and most mothers had not had a previous preterm birth. In both cohorts, any obstetric intervention’ occurred in 38% of births, 21% were induced deliveries and 17% were prelabor cesarean sections. Overall, variable colinearity was low (variance inflation factor between 1.00-1.9). In the univariable analysis of the derivation cohort, ‘any obstetric intervention’ was not significantly associated with LP birth (RR, 0.96; 95% confidence interval [CI], 0.85e1.09). Prelabor cesarean section was positively associated with LP birth (RR, 1.30; 95% CI, 1.21e1.40) and induction was negatively associated with LP birth (RR, 0.76; 95% CI, 0.65e0.89). For our primary analysis, adjustment for maternal and obstetric factors known
or suspected to be associated with preterm birth identified that ‘any obstetric intervention’ was associated with a lower likelihood of LP birth relative to term birth in the derivation cohort (RR, 0.65; 95% CI, 0.57e0.74). For our secondary analysis, adjusted risk ratio estimates for induction and prelabor cesarean section were also negatively associated with LP birth relative to term birth (RR, 0.71; 95% CI, 0.61e0.82 and RR, 0.66; 95% CI, 0.59e0.74 respectively) (Table 2). Exploring the adjusted association between obstetric interventions by week of gestational age at birth in the derivation cohort revealed that ‘any obstetric interventions’, induction and prelabor cesarean section were negatively associated with LP birth through the 36th week of gestation with cesarean section reaching statistical nonsignificance at 37 weeks’ gestation (Table 3).
TABLE 3
Associations between obstetrical interventions by week of gestation relative to term birth in the derivation cohort 34 wks a
35 wks
36 wks
a
a
37 wks
Variable
aRR
aRR
aRR
aRRa,b
Any obstetric intervention
0.49 (0.39e0.62)
0.57 (0.49e0.68)
0.65 (0.57e0.74)
0.92 (0.83e1.03)
Induction
0.43 (0.32e0.58)
0.61 (0.51e0.74)
0.74 (0.65e0.85)
0.81 (0.75e0.88)
Prelabor cesarean section
0.73 (0.58e0.93)
0.63 (0.53e0.76)
0.59 (0.51e0.68)
0.79 (0.72e0.87)
aRR, adjusted risk ratio. a
Adjusted for smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age; b aRR for the 37th week gestation calculated by considering term gestation to be 380⁄7 to 406⁄7 weeks.
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
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TABLE 4
Associations between maternal and fetal factors and LP gestational age at birth Derivation cohort
Validation cohort
uRR
aRR
uRR
aRRa
<20
1.18 (1.08e1.28)
1.06 (0.98e1.16)
1.09 (0.99e1.19)
1.00 (0.91e1.10)
20-24
1.02 (0.97e1.08)
1.02 (0.97e1.07)
1.06 (1.01e1.10)
1.06 (1.01e1.11)
25-34
Ref
Ref
Ref
Ref
35-39
1.11 (1.05e1.17)
1.06 (1.01e1.12)
1.14 (1.08e1.20)
1.10 (1.05e1.15)
>40
1.34 (1.23e1.46)
1.15 (1.06e1.25)
1.44 (1.33e1.57)
1.25 (1.16e1.34)
1 (lowest)
Ref
Ref
Ref
Ref
2
1.05 (0.97e1.14)
1.08 (1.03e1.13)
1.09 (1.03e1.16)
1.06 (1.00e1.11)
3
1.09 (0.98e1.20)
1.08 (1.01e1.16)
1.09 (1.02e1.17)
1.04 (0.99e1.10)
4
1.10 (1.00e1.21)
1.05 (0.99e1.12)
1.11 (1.04e1.19)
1.05 (1.00e1.10)
5 (highest)
1.15 (1.04e1.27)
1.10 (1.03e1.18)
1.14 (1.07e1.22)
1.07 (1.01e1.13)
Ref
Ref
Ref
Ref
Maternal characteristics
a
Maternal age, y
Material deprivation index quintiles
Social deprivation index quintiles 1 (lowest) 2
1.02 (0.97e1.07)
1.02 (0.98e1.07)
1.01 (0.96e1.06)
1.03 (0.98e1.09)
3
1.04 (0.99e1.09)
1.05 (1.00e1.10)
1.03 (0.97e1.09)
1.05 (0.99e1.11)
4
1.02 (0.95e1.10)
1.05 (0.99e1.11)
1.02 (0.96e1.08)
1.04 (0.99e1.10)
5 (highest)
1.05 (0.97e1.14)
1.09 (1.02e1.16)
1.03 (0.96e1.11)
1.07 (1.01e1.12)
Multifetal pregnancy
8.70 (7.99e9.46)
6.28 (5.85e6.74)
8.89 (8.19e9.64)
6.18 (5.74e6.64)
Smoking during pregnancy
1.35 (1.26e1.45)
1.28 (1.21e1.36)
1.41 (1.33e1.49)
1.34 (1.28e1.41)
Previous cesarean section
1.06 (1.01e1.12)
1.28 (1.16e1.40)
1.05 (0.99e1.12)
1.28 (1.18e1.39)
One
2.71 (1.88e3.89)
2.93 (2.27e3.78)
2.52 (1.78e3.57)
2.70 (2.14e3.41)
Multiple
2.58 (1.63e4.10)
2.77 (1.85e4.15)
2.60 (1.65e4.09)
2.78 (1.80e4.32)
Nuliparous
Ref
Ref
Ref
Ref
Primiparous
0.80 (0.76e0.84)
0.68 (0.63e0.73)
0.81 (0.77e0.85)
0.70 (0.66e0.74)
Multiparous
0.94 (0.89e1.00)
0.68 (0.62e0.74)
0.94 (0.88e1.00)
0.68 (0.63e0.74)
Previous preterm birth
Parity
Maternal health problems Preexisting diabetes
2.55 (2.34e2.79)
2.04 (1.81e2.30)
2.37 (2.14e2.64)
1.92 (1.74e2.12)
Gestational diabetes
1.60 (1.50e1.71)
1.32 (1.22e1.43)
1.65 (1.52e1.79)
1.39 (1.28e1.51)
Chronic hypertension
2.72 (2.43e3.05)
1.52 (1.30e1.78)
2.56 (2.32e2.83)
1.50 (1.33e1.69)
Infection during pregnancy
1.30 (1.07e1.60)
1.21 (1.03e1.42)
1.21 (0.95e1.55)
1.19 (1.00e1.42)
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
For our exploratory analysis, most of the hypothesized risk factors for preterm birth were independently associated with LP gestational age at birth in
the derivation cohort (Table 4). The strongest associated risk factor for LP gestational age at birth was multifetal pregnancy (RR, 6.28; 95% CI, 5.85e6.74)
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(continued)
followed by placenta previa (RR, 4.35; 95% CI, 3.88e4.89), preeclampsia (RR, 3.32; 95% CI, 3.05e3.60) and previous preterm birth (RR, 2.93; 95% CI,
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TABLE 4
Associations between maternal and fetal factors and LP gestational age at birth (continued) Derivation cohort Maternal characteristics
uRR
Validation cohort a
aRR
uRR
aRRa
Obstetric complications Eclampsia
4.44 (3.33e5.93)
2.23 (1.58e3.16)
4.46 (2.95e6.73)
2.16 (1.52e3.08)
Preeclampsia
3.91 (3.58e4.27)
3.32 (3.05e3.60)
3.88 (3.58e4.21)
3.15 (2.86e3.47)
Placental previa
5.01 (4.53e5.53)
4.35 (3.88e4.89)
4.93 (4.29e5.66)
4.42 (3.86e5.06)
Uterine bleeding
4.01 (3.44e4.68)
1.83 (1.59e2.11)
4.05 (3.47e4.71)
1.85 (1.63e2.10)
Placental abruption
4.34 (3.67e5.14)
2.05 (1.68e2.50)
4.47 (3.79e5.27)
2.33 (2.00e2.72)
Cord prolapse
1.56 (1.07e2.27)
0.81 (0.52e1.28)
2.22 (1.66e2.97)
1.60 (1.21e2.12)
Chorioamnionitis
1.22 (0.88e1.69)
1.12 (0.84e1.49)
1.04 (0.69e1.57)
1.09 (0.81e1.46)
Breech presentation
2.69 (2.54e2.84)
2.08 (1.96e2.22)
2.68 (2.53e2.84)
2.06 (1.93e2.21)
Small for gestational age (10th percentile)
1.14 (1.03e1.26)
1.04 (0.95e1.13)
1.16 (1.06e1.26)
1.05 (0.98e1.13)
aRR, adjusted risk ratio; LP, late preterm; ref, reference; uRR, unadjusted risk ratio. a
Adjusted for induction, smoking, material and social deprivation index, maternal age at delivery, parity, multifetal pregnancy, previous cesarean section, number of previous preterm births; preexisting diabetes, gestational diabetes, chronic hypertension, gestational hypertension, infection during pregnancy, preeclampsia, eclampsia, placenta previa, uterine bleeding, placental abruption, cord prolapse, chorioamnionitis, breech presentation and small for gestational age.
Bassil. Obstetric interventions and late preterm birth. Am J Obstet Gynecol 2014.
2.27e3.78). Several potentially modifiable risk factors were also associated with LP gestational age at birth including smoking during pregnancy (RR, 1.28; 95% CI, 1.21e1.36), previous cesarean section (RR, 1.28; 95% CI, 1.16e1.40) and high material (RR, 1.1; 95% CI, 1.03e1.18) and social (RR, 1.09; 95% CI, 1.02e1.16) deprivation indices. Repeating the primary and secondary analyses using the validation cohort led to similar findings (Tables 2-4).
C OMMENT We have used population based data from the largest province in Canada, to examine the magnitude of the association between obstetrical interventions and LP birth taking into account numerous known or suspected maternal and obstetrical risk factors for preterm birth. We have identified that induction and prelabor cesarean section were associated with a lower likelihood of LP birth relative to term birth for pregnancies with similar maternal and fetal risk. Further, this trend persisted through each LP gestational week up to 37 weeks. We have also identified several potentially modifiable risk factors which were associated
with LP birth, independent of obstetrical interventions, including previous cesarean section, smoking during pregnancy and high social and material deprivation. There has been concern that the escalation in LP birth over the past 20 years may be related to obstetric interventions and iatrogenic preterm birth.17 In Canada, the overall rate of cesarean delivery increased from 21.9% in 2001/2002 to 27.8% in 2009/2010.18 A recent multicountry analysis that aimed to understand the main drivers for the increase in the preterm birth rate over time identified that cesarean section and labor induction together accounted for approximately 20% of the change in LP birth between 1989 and 2004.19 However, maternal and fetal health problems are also increasing and expedited delivery through obstetric intervention in the setting of maternal or fetal compromise is generally accepted practice to avoid potentially disastrous maternal or neonatal outcomes.20 Overall rates of stillbirth and perinatal death in the US have decreased in parallel to the increase in LP births prompting some to argue that obstetric intervention may be preventing stillbirth and perinatal
death.21,22 Our findings add to this literature by suggesting that obstetrical care providers may be preferentially avoiding interventions to bring about LP birth in the setting of equivalent maternal and obstetric risk. We speculate that increased awareness among obstetric care providers about the harms of unnecessary LP birth may be a contributing factor. Another contributing factor may be elective cesarean section and induction which obstetric care providers may be more liberal with in the term than in the late preterm period. We have also identified several potentially modifiable factors which were independently associated with LP birth and may be useful targets for interventions to reduce LP birth. Consistent with other studies, previous cesarean section was associated with a 28% increased likelihood of LP birth suggesting that efforts to minimize term and preterm cesarean sections may decrease risk of LP birth in subsequent pregnancies.23-25 Smoking during pregnancy was associated with a 30% increased likelihood of LP birth. Strengths of our study include the clinical richness of the BORN
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Information System, which allowed for more thorough adjustment for maternal and obstetric risk factors. The magnitude of the change of the association between obstetric interventions and LP birth before and after adjustment for maternal and obstetric risk factors underscores the influence that such risk factors likely have on care provider decisions around obstetric interventions. Population based data also allowed us to use a validation cohort to verify our findings and minimize risk of spurious findings from multiple hypothesis testing.26 GEE modeling allowed us to account for clustering of obstetric interventions, which have been documented to vary considerably between hospitals.27 Our study has several limitations. Although a validation exercise has examined our primary outcome and primary exposure variables, several of the variables used in our analysis have not been validated raising the potential for coding error or misclassification.11 Induction and prelabor cesarean section were coded as mutually exclusive categories to capture the obstetric intervention that initiated the birth process. This resulted in a lower than expected frequency of cesarean sections since those that were proceeded by spontaneous labor or induction of labor were not included in the prelabor cesarean variable. It is also possible that our findings may have been influenced by incomplete adjustment. However, when we repeated our primary analysis using only the 32% of pregnancies with no identified risk factor for LP birth, the effect sizes were similar to our primary analysis (data not shown). We also considered that our finding of a negative association between obstetric interventions and LP birth may be reflective of increased risk of obstetrical interventions past 40 weeks gestation and our definition of “term” pregnancy included women up to 40 6/7 weeks’ gestation. However, a sensitivity analysis excluding births over 40 weeks’ gestation resulted in similar findings to our primary analysis (data not shown). Our findings suggest that over the past 7 years, the likelihood of birth associated
www.AJOG.org with obstetric interventions in Ontario was lower in the LP period than the term period once maternal and obstetric risk factors were taken into account. Obstetric care providers may be preferentially not intervening to bring about birth before term in the setting of equivalent maternal and obstetric risk. Although ongoing vigilance to avoid unnecessary late preterm obstetric interventions is warranted, strategies focusing on modifiable risk factors for LP birth may be helpful including minimizing unnecessary prelabor cesarean sections, smoking cessation, and reducing material and social deprivation. ACKNOWLEDGMENTS Support for this study was provided by both the Physician Services Incorporated Foundation and the St. Michael’s Hospital AFP Innovation Fund. Funding agencies had no role in the design, collection, analysis or interpretation of results in this study. We would also like to acknowledge the following individuals for their technical, administrative, and statistical support of this study: Sharmilaa Kandasamy, Research Coordinator II, Employed and Funded by the Department of Paediatrics, St. Michael’s Hospital Julie DeGroot, Clinical Research Project Manager, Employed and Funded by the Pediatric Outcomes Research Team, Hospital for Sick Children Rosane Nisenbaum, Senior Biostatistician, Employed and Funded by the Applied Health Research Centre, St. Michael’s Hospital
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