Risk factors for antepartum and intrapartum stillbirth: a population-based study

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OBSTETRICS

Risk factors for antepartum and intrapartum stillbirth: a population-based study Darios Getahun, MD, MPH; Cande V. Ananth, PhD, MPH; Wendy L. Kinzler, MD

S

tillbirth accounts for a sizable proportion of perinatal mortality for which the etiology remains obscure.1 Despite an overall decline in the stillbirth rate between 1981 and 2000 in the United States,2,3 large racial disparities persist.2 A 2-fold increased risk in perinatal mortality rate among African Americans as compared to whites has been documented in recent years.1 Several studies have reported many risk factors to be associated with stillbirth including advanced maternal age,2,4,5 multiparity,4 maternal race (African American and Hispanic women),5,6 low socioeconomic status,5,7,8 obesity,5,9,10 smoking during pregnancy,8 inadequate prenatal care,6 maternal medical and obstetrical complications,7,11 and previous stillbirth.12,13 However, relatively little is known about racial disparity in risk factors for overall stillbirth, as well as differences in stillbirth that occur during the antepartum versus intrapartum periods. We therefore examined the race-specific

From the Division of Epidemiology and Biostatistics (Drs. Getahun and Ananth) and Division of Maternal-Fetal Medicine (Dr. Kinzler), Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ. Received June 15, 2006; revised Sept. 16, 2006; accepted Sept. 19, 2006. Reprints: Darios Getahun, MD, MPH, Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine, and Denistry, New Jersey-Robert Wood Johnson Medical School, 125 Paterson St, New Brunswick, NJ 08901-1977. [email protected] Drs. Getahun and Ananth are supported in part through a grant (R01-HD038902) from the National Institutes of Health awarded to Dr. Ananth. 0002-9378/$32.00 © 2007 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2006.09.017

To examine disparities in risk factors for stillbirths and its occurrence in the antepartum versus intrapartum periods. A population-based, cross-sectional study using data on women that delivered singleton births between 20 and 43 weeks in Missouri (1989-1997) was conducted (n ⫽ 626,883). Hazard ratios and 95% confidence intervals were derived from regression models and population attributable fractions were estimated to examine the impact of risk factors on stillbirth. Among African Americans, risks of antepartum and intrapartum stillbirth were 5.6 and 1.1 per 1,000 singleton births, respectively; risks among whites were 3.4 and 0.5 per 1,000 births, respectively. Maternal age ⱖ35 years, lack of prenatal care, prepregnancy body mass index (BMI) ⱖ 30 kg/m2, and prior preterm or small-for-gestational age birth were significantly associated with increased risk for antepartum stillbirth among whites, but not African Americans. BMI ⱕ18.5 kg/m2 was associated with antepartum and intrapartum stillbirth among African Americans, but not whites. The presence of any congenital anomaly, abruption, and cord complications were associated with antepartum stillbirth in both races. Premature rupture of membranes was associated with intrapartum stillbirth among whites and African Americans, but intrapartum fever was associated with intrapartum stillbirth among African Americans. These risk factors were implicated in 54.9% and 19.7% of antepartum and intrapartum stillbirths, respectively, among African American women, and in a respective 46.6% and 11.9% among white women. Considerable heterogeneity in risk factors between antepartum and intrapartum stillbirths is evident. Knowledge on timing of stillbirth specific risk factors may help clinicians in decreasing antepartum and intrapartum stillbirth risks through monitoring and timely intervention. Key words: antepartum stillbirth, etiology, intrapartum stillbirth, risk factors stillbirth risks and its timing (antepartum versus intrapartum stillbirth) among singleton pregnancies. While antepartum and intrapartum stillbirths may share overlapping etiologies, it is likely that both outcomes may differ in many respects and that disparity in risk factors may exist.

M ATERIALS AND M ETHODS Data source and cohort composition We conducted a population-based, cross-sectional study among singleton pregnancies from 1989 to 1997 in the state of Missouri. Data were obtained from the Missouri live birth and fetal death files that have been assembled by the Missouri Department of Health and Senior Services. The data includes information on maternal sociodemographic

characteristics, behavioral factors, medical history, obstetrical complications, as well as fetal outcomes. Gestational age in these data files was largely estimated from the date of last menstrual period (LMP). When the date of LMP was unavailable, or when the calculated gestational age (based on LMP) was considered biologically unreasonable (eg, extremely low birthweight at term), a clinical estimate of gestational age, also contained on the data files, was used instead.14 The principal outcome variables examined were antepartum stillbirth (the death of a fetus prior to onset of labor) and intrapartum stillbirth (the death of a fetus during labor and delivery) between 20-43 weeks of gestation. Self reported maternal race was grouped as white (white, nonHispanic) and African

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FIGURE 1

Flow diagram of data exclusions, Missouri 1989-1997

www.AJOG.org tus, and renal disease), obstetrical complications (preeclampsia, premature rupture of membranes [PROM], chorioamnionitis, placental abruption, placenta previa, and excessive vaginal bleeding other than placental abruption and placenta previa related bleeding), fetal gender, prior preterm birth, prior and current small-for-gestational age (SGA, defined as birthweight less than the 5th or 10th percentiles) birth, any form of congenital (chromosomal and nonchromosomal) anomaly, cord complications and fetal distress. Since PROM and fever (a surrogate for chorioamnionitis) are potential risk factors that are not always independent from one other, we analyzed PROM in conjunction with fever. SGA birth was estimated based on 1989-1997 gender-specific normogram (internal standard).

Data exclusions Of the 711,015 births in the state of Missouri between 1989 and 1997, we excluded sequentially (Figure 1) multiple pregnancies and pregnancies that ended at ⬍ 20 and ⱖ 43 completed weeks. The latter exclusions were necessary to avoid errors in gestational age estimation.15 We further excluded pregnancies to races other than whites or African American due to small sample. Finally, we excluded records with missing data on the timing of stillbirth. After all exclusions, the final analytic cohort comprised of 626,883 singleton pregnancies that resulted in a live birth or stillbirth. American (black, nonHispanic). Factors that were considered to be associated with stillbirth included maternal age (⬍ 20, 20-24, 25-29, 30-34, and ⱖ 35 years), maternal education (⬍ 8, 8-11, and ⱖ 12 years of completed schooling), parity (nulipara, multipara), marital status (married, single), period during pregnancy when prenatal care was initiated (early or first trimester, late or any time after the first trimester, no care), smoking during pregnancy (yes or no), prepregnancy body mass index (⬍ 18.5, 18.5-25, 25-30, and ⱖ 30 kg/m2), excessive pregnancy weight gain (ⱖ 41 lbs; yes or no), maternal medical conditions (chronic hypertension, diabetes melli500

Statistical analysis We first examined the distribution of risk factors for stillbirth. Rates of antepartum and intrapartum stillbirth were compared in relation to maternal characteristics. We repeated the analysis separately for whites and African Americans. Race-specific crude hazard ratio (HR) and 95% confidence interval (CI) for antepartum and intrapartum stillbirth for each risk factor was estimated from Cox proportional hazards model.16,17 The outcome variable was “time-to-event,” with the “event” being a stillbirth, and “event-time” being gestational week at the time of

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birth. Subsequently, adjusted hazard ratios were derived to assess the relationship between stillbirths and potential risk factors for each race group. Departure from the proportionality assumption in these models was checked graphically. We examined race-specific associations between maternal sociodemographic, behavioral, medical, and obstetrical risk factors and antepartum and intrapartum stillbirths. The completeness of data in birth certificate records varies depending specific variable. Since excluding missing information on potential risk factors may result in incorrect estimation of their association with the outcome, we retained missing values in all analysis. To assess the impact of missing values in the estimate of the associations, we repeated the analysis after excluding missing values. In order to examine race disparity in stillbirth risk, we compared the antepartum and intrapartum stillbirth risks among African American and white women. Population attributable fraction (PAF) was calculated to quantify the proportion of antepartum and intrapartum stillbirth that could have been prevented if a particular factor had not occurred. To estimate the adjusted odds ratio, we repeated the analysis using multivariable logistic regression method. We used the formula PAF ⫽ pdi [(ORi-1)/ORi], where ORi is the adjusted odds ratio for the exposure category, and “pdi” represents the proportion of cases in the population from the ith exposure category.18 The study was approved by the ethics committee of the Institutional Review Board of UMDNJ-Robert Wood Johnson Medical School, NJ. All statistical analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC).

R ESULTS The overall incidence of stillbirth was 5.5 (n ⫽ 3465) per 1000 singleton births. The incidences of antepartum and intrapartum stillbirth were 3.7 (n ⫽ 2337) and 0.6 (n ⫽ 384) per 1000 singleton births, respectively. The rate of missing data on stillbirth was 1.1 (n ⫽ 744) per 1000 singleton births. Rates of antepar-

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www.AJOG.org tum and intrapartum stillbirth among African Americans were 5.6 and 1.1 per 1000 births, respectively, and the corresponding rates among whites were 3.4 and 0.5 per 1000 births, respectively. Table 1 shows the distribution of maternal and fetal characteristics by live birth and stillbirth subtypes. Compared with women that delivered a live birth, those with antepartum and intrapartum stillbirths were more likely to be older (ⱖ 35 years), multiparous, African American, unmarried, less educated, smokers, without prenatal care, either underweight or obese, have small-for-gestational age births at ⬍ 5th and ⬍ 10th percentiles, and less likely to have gained excess weight during their pregnancy. Table 2 shows the rate and adjusted hazard ratio for antepartum and intrapartum stillbirth in relation to maternal and fetal characteristics. Among whites, risk for antepartum stillbirth was associated with advanced maternal age, lower education, multiparity, late initiation or no prenatal care, being either overweight or obese, and prior preterm or SGA births, and current SGA birth. Among African Americans, risk for antepartum stillbirth was strongly associated with women being less educated, multiparous, being either underweight or overweight, and SGA birth. Among whites, risk of intrapartum stillbirth was significantly associated with unmarried status, multiparity, and SGA birth at ⬍ 10th percentile. Among African Americans, risk for intrapartum stillbirth was significantly associated with lower education and being underweight. Excessive weight gain during pregnancy was not associated with antepartum and intrapartum stillbirths in white and African American women. African American versus white disparity in antepartum stillbirth was evident among pregnant women who were between 20 and 30 years of age, with ⬍ 8 and ⱖ 12 years of schooling, BMI ⬍ 25 kg/m2, single, multiparous, smoking, and male fetus pregnancy. African American versus white disparity in intrapartum stillbirth has been noted among pregnant women that were smoking and had SGA birth at ⬍ 5th percentile.

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TABLE 1

Distribution of maternal and fetal characteristics among singleton births by live birth and stillbirth categories: Missouri, 1989-1997 Stillbirths

Characteristics

Live births n ⴝ 624,162

Antepartum n ⴝ 2,337 (0.4%)

Intrapartum n ⴝ 384 (0.06%)

Maternal age (years) (%)

P value .004

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

⬍ 20

13.9

14.4

19.5

20-24

26.7

27.0

28.7

25-29

29.3

24.5

21.3

30-34

21.1

20.6

15.9

ⱖ 35

9.0

12.8

14.1

Missing

0.0

0.7

0.3

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

⬍.001

Maternal education (years) (%)

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

⬍8

1.3

8.6

9.4

8-11

18.2

20.8

22.7

ⱖ 12

80.4

70.6

67.7

0.2

0.3

0.2

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

Missing

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

⬍.001

Maternal race (%)

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

White

83.6

75.4

70.1

African American

16.3

24.6

29.9

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

⬍.001

Parity (%)

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

Nuliparity

39.2

31.5

28.4

Multiparity

60.8

68.5

71.6

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

⬍.001

Marital status (%)

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

Married

69.7

61.8

55.5

Unmarried

30.0

38.2

44.5

0.1

0.0

0.0

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

Missing

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

⬍.001

Smoking during pregnancy (%)

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

Yes

22.9

27.4

27.3

No

77.7

70.7

71.6

0.4

1.9

1.0

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

Missing

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

⬍.001

Prenatal care (%)

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

Early initiation

82.4

73.0

73.4

Late initiation or no care

16.5

21.1

17.5

1.1

6.0

9.1

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

Missing

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

⬍.001

Body mass index (%)

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

⬍ 18.5 kg/m

7.6

6.2

9.6

18.5-24.9 kg/m

58.2

47.6

49.2

25-29.9 kg/m

18.4

18.1

15.6

ⱖ 30 kg/m

13.2

16.4

13.5

2.6

11.7

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

Missing

12.0

Continued on page 502.

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TABLE 1

Distribution of maternal and fetal characteristics among singleton births by live birth and stillbirth categories: Missouri, 1989-1997 Continued from page 501. Stillbirths

Characteristics

Live births n ⴝ 624,162

Antepartum n ⴝ 2,337 (0.4%)

Intrapartum n ⴝ 384 (0.06%)

P value ⬍.001

Pregnancy weight gain (%)

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

Excessive (ⱖ 41 lb)

18.8

7.9

6.3

Inadequate/adequate (⬍ 41 lb)

77.8

78.3

77.9

3.4

13.8

15.8

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

Missing

Figure 2 shows gestational age specific rates (panel A) and hazard ratios (panel B) for antepartum stillbirth among white and African American women. The hazard ratio for antepartum stillbirth was lower among African Americans compared to whites at preterm gestational ages with cross-over in risk at term gestation. Among pregnancies complicated by intrapartum stillbirth, gestational age-specific stillbirth hazard ratios were comparable between both races (data not shown).

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

⬍.001

Gender (%)

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

Male

51.3

51.1

55.2

Female

48.7

48.1

44.0

Missing

0.0

0.8

0.8

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

⬍.001

Prior preterm/SGA birth (%)

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

Yes

1.4

2.9

5.7

No

98.6

97.1

94.3

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

⬍.001

SGA birth (%)

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

⬍5th percentile

4.6

25.2

15.6

⬍10th percentile

9.3

35.5

24.3

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

⬍.001

Preterm birth (%)

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

⬍32 weeks

1.9

48.4

72.4

⬍34 weeks

3.3

57.2

76.6

⬍37 weeks

10.7

71.5

84.1

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

SGA, small-for-gestational age.

Table 3 shows associations between maternal medical and obstetrical as well as fetal conditions with stillbirth subtypes. Among whites, any congenital anomaly, placental abruption, and cord complications were significantly associated with antepartum stillbirth. Among African Americans, any form of congenital anomaly, chronic hypertension, abruption, other excessive vaginal bleeding during pregnancy, and cord complications were significantly associated with antepartum stillbirth. Among whites, PROM regardless of fever, abruption, other excessive bleeding during pregnancy, renal disease, and cord complications were significantly associated with intrapartum stillbirth. Among African Americans, congenital anomaly, PROM with or without fever, fever only, abruption, and cord compli502

cations were significantly associated with intrapartum stillbirth. A strong race disparity in antepartum stillbirth was apparent in pregnancies complicated by chronic hypertension, pregnancy-induced hypertension, PROM with or without fever, and placental abruption. Table 4 shows population attributable fractions for risk factors for stillbirth. The PAFs for antepartum and intrapartum stillbirths were much higher for African Americans (54.9% and 19.7%) as compared to whites (46.6% and 11.9%). In other words, 45.1% and 80.3% of antepartum and intrapartum stillbirth cases among African Americans, and 53.4% and 88.1% of antepartum and intrapartum stillbirth cases among whites remained unexplained by the risk factors.

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D ISCUSSION Our large population-based study corroborates findings from several earlier studies on potential risk factors for antepartum and intrapartum stillbirths, including maternal age, lower education, unmarried status, smoking during pregnancy, being overweight and obese, and maternal medical and obstetrical as well as fetal risk factors.8,9,11,19 This study additionally provides insights into the patterns of racial disparity in risk factors for both antepartum and intrapartum stillbirths. Recent studies have reported a declining trend in stillbirth rates in the United States with African American women continue to have a higher incidence rate as compared with white women.2,3 However, very little is known about racial disparity in risk factor profiles for antepartum and intrapartum stillbirth. An examination of the racial disparity by stillbirth subtypes (antepartum and intrapartum stillbirth) revealed that not only are African American women at increased risk of antepartum and intrapartum stillbirth compared with white women, but the magnitude of associations with most risk factors were also relatively larger. Little and Weinberg8 reported in their case control study that women with higher body mass index are at increased risk for both antepartum and intrapartum stillbirth though with greater risks for intrapartum stillbirth. Equally, Stephansson et al9 reported, using data from a relatively homogenous Swedish population, an increased risk of late antepartum stillbirth (at ⱖ 28 weeks of gestation) with higher maternal prepreg-

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TABLE 2

Race-specific association between maternal and fetal factors and stillbirths: Missouri, 1989-1997 Antepartum stillbirths Whites Characteristics

Rate (%)

Intrapartum stillbirths African Americans

HR (95% CI)

Rate (%)

HR (95% CI)

African Americans vs. Whites HR (95% CI)

Whites Rate (%)

African Americans HR (95% CI)

Rate (%)

HR (95% CI)

African Americans vs. Whites HR (95% CI)

Maternal age (years)

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

⬍ 20

0.37

0.9 (0.7, 1.0)

0.42

0.7 (0.6, 1.0)

1.3 (0.9, 1.7)

0.07

0.6 (0.4, 1.1)

0.13

0.9 (0.4, 2.0)

20-24

0.34

1.0*

0.53

1.0*

1.2 (1.0, 1.6)

0.06

1.0*

0.10

1.0*

0.9 (0.5, 1.6)

25-29

0.27

1.0 (0.8, 1.1)

0.58

1.0 (0.8, 1.4)

1.5 (1.1, 1.9)

0.04

0.8 (0.5, 1.2)

0.07

0.6 (0.2, 1.4)

0.9 (0.4, 2.2)

30-34

0.33

1.1 (0.9, 1.2)

0.67

1.0 (0.8, 1.5)

1.3 (0.9, 1.8)

0.04

0.6 (0.4, 1.0)

0.10

0.7 (0.3, 1.7)

1.0 (0.4, 2.8)

ⱖ 35

0.49

1.5 (1.2, 1.8)

0.90

1.2 (0.8, 1.8)

1.1 (0.7, 1.0)

0.08

0.9 (0.5, 1.6)

0.25

0.8 (0.3, 2.3)

1.5 (0.5, 4.5)

1.4 (0.7, 3.6)

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

Maternal education

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

⬍8

1.08

2.4 (1.9, 3.0)

2.00

2.3 (1.7, 3.2)

1.4 (1.0, 2.1)

0.15

1.7 (0.9, 3.4)

0.52

2.6 (1.1,6.4)

1.8 (0.5, 5.2)

8-11

0.40

1.2 (1.0, 1.5)

0.46

1.1 (0.9, 1.4)

1.2 (0.9, 1.5)

0.07

1.5 (0.9, 2.3)

0.09

1.4 (0.7, 2.8)

1.2 (0.6, 2.4)

ⱖ 12

0.30

1.0*

0.51

1.0*

1.3 (1.1, 1.5)

0.05

1.0*

0.09

1.0*

0.9 (0.6, 1.4)

0.41

1.0 (0.9, 1.1)

0.55

0.9 (0.7, 1.2)

1.2 (1.0, 1.4)

0.07

1.5 (1.0, 2.1)

0.11

0.8 (0.4, 1.7)

0.9 (0.6, 1.4)

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

Unmarried status

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

Parity

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

Nullipara

0.28

1.0*

0.39

1.0*

1.2 (0.9, 1.5)

0.04

1.0*

0.07

1.0*

0.8 (0.4, 1.7)

Multipara

0.37

1.3 (1.1, 1.4)

0.66

1.5 (1.2, 1.9)

1.3 (1.1, 1.5)

0.06

1.4 (1.0, 1.9)

0.14

0.7 (0.8, 2.9)

1.1 (0.8, 1.7)

0.47

1.3 (1.1, 1.5)

0.50

1.0 (0.8, 1.2)

1.0 (0.8, 1.3)

0.06

1.1 (0.7, 1.6)

0.09

0.7 (0.3, 1.3)

0.8 (0.4, 1.7)

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

Late/no prenatal care

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

Body-mass index

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

⬍ 18.5

0.27

0.7 (0.5, 1.0)

0.48

1.4 (1.1, 1.9)

1.6 (1.2, 2.2)

0.07

1.0 (0.6, 1.6)

0.10

1.9 (1.0, 4.1)

1.6 (0.8, 3.4)

18.5-25

0.29

1.0*

0.42

1.0*

1.2 (1.0, 1.4)

0.05

1.0*

0.09

1.0*

1.0 (0.6, 1.6)

25-30

0.33

1.2 (1.1, 1.4)

0.51

1.2 (1.0, 1.6)

1.1 (0.8, 1.5)

0.05

1.0 (0.6, 1.5)

0.08

0.8 (0.3, 1.8)

0.7 (0.3, 1.7)

ⱖ 30

0.43

1.3 (1.1, 1.6)

0.58

1.2 (0.9, 1.5)

1.2 (0.9, 1.7)

0.05

0.7 (0.4, 1.2)

0.10

1.1 (0.5, 2.6)

1.4 (0.6, 3.6)

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

Excess weight gain

0.16

0.6 (0.5, 0.8)

0.14

0.4 (0.3, 0.6)

0.9 (0.5, 1.3)

0.02

0.5 (0.3, 0.9)

0.03

0.3 (0.1, 1.2)

0.5 (0.1, 2.4)

Smoking

0.43

1.0 (0.8, 1.1)

0.67

1.1 (0.8, 1.3)

1.2 (1.0, 1.6)

0.06

0.7 (0.4, 1.0)

0.18

1.6 (0.8, 3.2)

2.1 (1.1, 4.3)

Male gender

0.33

1.0 (0.9, 1.1)

0.57

1.1 (0.9, 1.3)

1.3 (1.1, 1.6)

0.05

1.1 (0.8, 1.6)

0.13

1.2 (0.7, 2.0)

1.1 (0.7, 1.7)

Prior preterm or SGA birth

0.69

1.3 (1.0, 1.9)

0.98

0.9 (0.5, 1.6)

1.1 (0.5, 2.4)

0.20

1.4 (0.6, 3.3)

0.40

1.6 (0.5, 5.0)

1.5 (0.3, 8.4)

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

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

Current SGA birth

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

⬍ 5th percentile

1.70

2.2 (1.8, 2.7)

1.33

1.7 (1.2, 2.4)

0.8 (0.6, 1.0)

0.10

0.8 (0.4, 1.6)

0.18

3.8 (0.9, 16.9) 3.4 (1.5, 7.7)

⬍ 10th percentile

1.32

3.0 (2.5, 3.6)

0.97

1.6 (1.2, 2.2)

0.9 (0.7, 1.1)

0.09

1.9 (1.1, 3.1)

0.11

0.5 (0.1, 2.1)

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

1.5 (0.7, 2.9)

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

Rates correspond to stillbirth rate per 100 total births. Hazard ratios were adjusted for variables in this table and that shown in table 3. SGA, small-for-gestational age. * Reference.

nancy body mass index as compared with lean women (body mass index ⱕ 19.9 kg/m2). Our finding of increased association between overweight and obese white women and antepartum stillbirths concurs with these studies. This study provides additional interesting findings in that among African American women, lean body weight (⬍ 18.5 kg/ m2) was associated with antepartum

and intrapartum stillbirth. We also showed a 60% excess risk of antepartum and intrapartum stillbirth among African American compared with white underweight women. Although the underlining reason for the race disparity cannot be explained by this study, targeting this segment of pregnant women may provide an opportunity to reduce the disparity gap. Conversely, obesity was associated with

antepartum stillbirths among white but not among African American women. Excessive weight gain during pregnancy was not associated with risk in both races. Although our original analysis was limited to gestational age between 20 and 43 completed weeks, restricting the data to late antepartum stillbirths (at ⱖ 28 weeks) further strengthened these associations (data not shown).

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TABLE 3

Association between maternal and fetal explained conditions and stillbirths: Missouri, 1989-1997 Antepartum stillbirth Whites Conditions

Rate (%) HR (95% CI)

Any congenital

3.17

Intrapartum stillbirth African Americans African Whites Americans vs. Rate Whites Rate (%) HR (95% CI) HR (95% CI) (%) HR (95% CI)

4.7 (3.7, 5.9) 3.54

3.9 (2.4, 6.3)

1.0 (0.7, 1.6)

African Americans Rate (%) HR (95% CI)

African Americans vs. Whites HR (95% CI)

0.86 10.9 (7.3, 16.2) 1.31 12.8 (6.0, 27.3) 1.1 (0.5, 2.3)

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

Anomaly

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

Diabetes mellitus

0.37

0.8 (0.5, 1.1) 0.76

0.8 (0.4, 1.4)

1.5 (0.8, 3.1)

0.07

0.6 (0.3, 1.5) 0.08

0.6 (0.1, 4.6)

0.8 (0.1, 8.2)

Chronic hypertension 0.84

1.2 (0.8, 1.8) 2.04

1.7 (1.0, 2.8)

1.9 (0.9, 4.1)

0.21

2.2 (0.9, 5.6) 0.37

3.0 (0.6, 13.8) 1.3 (0.1, 30.5)

PIH*

0.7 (0.5, 0.9) 0.98

1.2 (0.8, 1.8)

1.9 (1.2, 3.0)

0.07

0.7 (0.3, 1.4) 0.11

0.3 (0.1, 2.2)

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

0.41

1.1 (0.1, 11.0)

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

PROM/Maternal fever

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

PROM –No fever 0.46

0.5 (0.4, 0.8) 1.02

0.8 (0.5, 1.3)

1.7 (1.0, 3.2)

0.39

3.2 (2.1, 5.1) 0.86

5.0 (2.4, 10.7) 1.2 (0.6, 2.6)

No PROM - Fever 0.72

1.2 (0.8, 1.8) 0.83

1.0 (0.6, 1.9)

1.3 (0.6, 2.9)

0.18

1.8 (0.8, 4.0) 0.21

3.5 (1.1, 11.3) 1.8 (0.3, 10.1)

PROM and Fever 0.48

0.5 (0.1, 2.0) 1.46

1.8 (0.7, 4.6) 16.1 (1.9, 135.9) 1.03 11.6 (5.2, 25.8) 1.10

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

7.1 (1.6, 31.8) 0.5 (0.1, 3.1)

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

Placental abruption

4.69 10.2 (8.1, 12.9) 6.82 10.9 (7.4, 15.9) 1.5 (1.1, 2.1)

1.25 10.9 (7.1, 16.8) 2.03 26.6 (13.0, 54.2) 1.3 (0.7, 2.7)

Placenta previa

1.08

1.1 (0.6, 1.9) 0.80

0.3 (0.1, 2.3)

0.2 (0.0, 2.3)

0.39

1.7 (0.6, 4.7) 0.27

--

--

Excessive bleeding

1.59

1.3 (0.9, 1.9) 3.07

2.2 (1.2, 3.7)

1.8 (0.9, 3.6)

1.12

5.7 (3.5, 9.3) 0.30

--

--

Renal disease

0.66

0.9 (0.4, 2.2) 1.57

1.5 (0.5, 4.8)

3.8 (0.4, 33.7) 0.49

3.1 (1.0, 9.8) 1.26

--

--

Fetal distress

0.10

0.1 (0.1, 0.2) 0.05

0.1 (0.1, 0.2)

0.5 (0.2, 1.6)

0.10

0.8 (0.5, 1.2) 0.16

1.4 (0.7, 2.9)

1.6 (0.7, 3.8)

Cord complications

2.53

4.7 (3.3, 6.6) 3.09

3.5 (1.8, 6.9)

0.9 (0.4, 2.0)

1.03

9.9 (5.6, 17.5) 1.11

6.0 (1.8, 20.5) 0.7 (0.2, 2.9)

Any one condition

0.76

2.1 (1.6, 2.7) 1.00

1.9 (1.3, 2.8)

1.4 (1.1, 1.7)

0.23

5.3 (3.1, 8.9) 0.34

1.9 (0.8, 4.7)

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ‡ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................

1.4 (1.0, 1.7)

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

Rates correspond to stillbirth rate per 100 total births. Hazard ratios were adjusted for variables in this table and those shown in Table 2 * PIH (Pregnancy induced hypertension). ‡

Excludes placental abruption and placenta previa.

TABLE 4

Population attributable fraction for selected risks factors for antepartum and intrapartum stillbirth Antepartum stillbirth Selected characteristic

Whites %

African Americans %

Intrapartum stillbirth Whites %

African Americans %

Age ⱖ35 years or Parity ⱖ4

1.8

2.6

0.1

0.6

Smoking during pregnancy

0.1

0.6

0.0

0.7

Education ⬍8 years, No PNC

2.2

1.9

0.2

0.0

Underweight (⬍18.5 kg/m )

0.3

0.1

0.1

0.6

Chronic medical conditions

1.1

5.3

0.3

0.3

Preeclampsia/abruption

4.1

8.7

2.6

5.1

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

Small-for-gestational age birth

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

⬍10th centile

9.3

6.1

0.4

0.0

Any congenital anomaly

27.7

29.6

8.2

12.4

Total

46.6

54.9

11.9

19.7

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

PNC, prenatal care.

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Studies that have examined the risk of stillbirth by gestational age have reported risks to be higher at very preterm and postterm gestations compared with term gestations.20 The risk for antepartum stillbirth at ⱕ 30 weeks gestation was lower in African American compared to in white women (Figure 2). One explanation is the possibility of an artifact in early detection of fetal demise through better access to specialized care. Early identified fetal demise might be subjected to early intervention through induction of labor. Although we attempted to control for socioeconomic disparity using proxies such as maternal education and time at which prenatal care began, there is still the possibility that some unaccounted factors might have been responsible for this increase. Stillbirth is an important public health problem, the etiology of which is largely unknown. From a public health perspec-

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FIGURE 2

Race-specific rate and hazard ratio of antepartum stillbirth among singleton births by gestational age categories: Missouri, 1989-1997

A, Race-specific rate, B, hazard ratio.

tive, the association between lack of education, being overweight or obese, and lack of prenatal care among white women and lack of education and being underweight or overweight among black women and antepartum stillbirth is important. Increasing community awareness through education (modifiable factors) might contribute to reducing risks. Knowledge on race-specific risk factor profiles for stillbirth based on the timing of occurrence also has clinical importance. Early detection of less-modifiable risks resulting from placental abnormalities and other prenatal risk factors including premature rupture of membranes with or without fever and excessive bleeding may help clinicians in lowering risk through closely monitoring and timely intervention of the affected patient.

Our study has limitations. The birth certificate data are prone to some degree of underreporting of medical and obstetrical risk factors as well as recall bias of certain exposures (such as smoking during pregnancy).21-25 The observation that women with stillbirth may report smoking more often than women that have delivered a live born infant may lead to a differential misclassification bias with regard to smoking during pregnancy. Such misclassification, if present, will likely result in hazard ratios being driven away from null.26 Although congenital anomalies are well documented, etiological factors for stillbirth and the poor reliability and validity of birth defect reporting in birth certificate records27,28 prevented us from examining the association between individual birth defect and antepartum and intra-

partum stillbirths. An imposition of a moratorium on the publication of birth defect-related studies that utilize birth certificate data until the reliability and validity of this data has improved has been suggested.28 However, we showed data on overall congenital anomaly for the reason that although records on individual birth defect category may not be complete, completely ignoring the impact of birth defect on the association with stillbirth may limit the interpretation of the study finding. Nonetheless, interpretations of the findings with respect to congenital anomaly should be tempered with caution. An estimate of gestational age at extremes of pregnancy is most likely to be inaccurate in birth certificate files.24 For example, congenital malformations such as anencephaly and chro-

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mosomal anomalies, including trisomy 13 and 18, may not be compatible with life and may have led to fetal demise at an early gestation resulting in an inaccurate estimate of the timing of fetal demise. We excluded fetuses at ⬍ 20 weeks and ⱖ 44 weeks of gestation from the study to avoid errors in gestational age estimation. Therefore, the associations reported in this study may be conservative. Since data on other risk factors for stillbirths such as low socioeconomic factors,7 cocaine and drug use, genetic factors, medical (eg, systemic lupus erythomatosus, thyroid disorders, thrombophilias, and many more metabolic disorders) and psychosocial conditions were unavailable in the data set used for this study,29-31 we were unable to examine the extent to which these risk factors are associated with antepartum and intrapartum stillbirth. Therefore, our approach may not completely eliminate the confounding effect of these and other unmeasured factors, leaving a residual confounding. However, using the available data, we were able to demonstrate that risk factor profiles for stillbirth vary by race and timing (antepartum versus intrapartum) of birth. Further research is needed to examine maternal genetics, detailed medical and psychosocial domains to advance the understanding of these exposures to the risk for antepartum and intrapartum stillbirths. Birth certificate records are a major source of population-based data on maternal and infant health, but the completeness of data (Table 1) varies depending on specific factors. Overall, congenital anomaly, BMI, and weight gain during pregnancy are, in general, less complete and warrant a careful interpretation. Maternal medical and obstetrical risk factors that were examined were absent in up to 1% of records. Plurality was reported in all cases. To examine the impact of missing values on associations noted, we replicated the analysis after excluding missing values (not shown). These results were essentially unchanged from those shown. Since our objective was to examine risk factors for antepartum and intra506

www.AJOG.org partum stillbirth by race, missing data on the timing of stillbirth (21%, n ⫽ 744) was excluded from the analysis. However, in order to assess any bias due to missing data we conducted sensitivity analysis by reassigning the missing values on timing of stillbirth to antepartum stillbirths (not shown). The results were fairly similar to those shown. The strengths of the study include its population-based nature that includes a large number of pregnancies. Unlike many other birth certificate records that lack data on the timing of fetal death, the Missouri linked birth and fetal mortality data files contains this information in sizable proportion. The rate of missing data on the timing of fetal death was only 1.1 per 1000 singleton births.

C ONCLUSION The study reveals considerable heterogeneity in risk factors between antepartum and intrapartum stillbirths. Knowledge on timing of stillbirth specific risk factors may help clinicians in decreasing antepartum and intrapartum stillbirth risks through monitoring and timely interventions. f ACKNOWLEDGMENTS We are grateful to the Missouri Department of Health and Senior Services for graciously allowing us to use the state maternally linked longitudinal data file. We also thank Anthony Vintzileos, MD, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School for critically reviewing the manuscript and for offering suggestions that vastly improved its contents and thank Susan Fosber for her assistance during the preparation of the manuscript.

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