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ORIGINAL RESEARCH |
From the 1Department of Epidemiology, UMDNJ-School of Public Health, 2Division of Epidemiology and Biostatistics and 3Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey; and 4Department of Maternal and Child Health, University of Alabama at Birmingham, Birmingham, Alabama.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: The Missouri maternally linked cohort data set containing births from 1978 through 1997 was used. We identified the study group (women who experienced a stillbirth in the first pregnancy) and a comparison group (women who delivered a live birth in their first pregnancy) and compared the outcome (stillbirth) in the second pregnancy between the 2 groups.
RESULTS: We analyzed 404,180 women with information on first and second pregnancies (1,979 [0.5%] in the study arm, and 402,201 [99.5%] in the comparison arm). Of the 1,929 cases of stillbirths in the second pregnancy, 45 cases occurred in mothers with a history of stillbirth (stillbirth rate = 22.7/1000) and 1,884 in the comparison group (stillbirth rate 4.7/1,000, P < .001). The adjusted risk of stillbirth was almost 5-fold as high in women with a prior stillbirth (odds ratio 4.7, 95% confidence interval 3.3–6.6). Analysis across racial groups revealed that whites had lower absolute risk for stillbirth recurrence than African Americans (19.1/1,000 compared with 35.9/1,000, P < .05). The elevated stillbirth recurrence risk was confirmed after adjusting for potential confounders (odds ratio 2.6, 95% confidence interval 1.2–5.7).
CONCLUSION: History of stillbirth is associated with a 5-fold increase for subsequent stillbirth. The recurrence of stillbirth is almost tripled in African Americans as compared with whites.
LEVEL OF EVIDENCE: II-2
A useful approach that could strengthen our ability to formulate effective prevention measures vis-à-vis repetition of stillbirth is to delineate determinants of recurrence. It is well known that race influences baseline risk for stillbirth occurrence.1,5–10 Further, with increase in fetal number the baseline risk for stillbirth tends to be modified by race.1 Given this premise, it is therefore reasonable to expect racial variation regarding stillbirth recurrence as well. We undertook this study guided by the following working hypotheses: 1) women who experience a stillbirth have an elevated risk for subsequent stillbirth and 2) race is a determinant of stillbirth recurrence.
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MATERIALS AND METHODS |
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The Missouri maternally linked cohort data contains information on both live birth and fetal death for each sibling and provides a platform for a longitudinal study of birth outcomes for each pregnancy. Of the 1,577,082 births in Missouri from the period 1978 through 1997, we selected pregnancies that satisfied the following inclusion criteria (Fig. 1): 1) singleton births, 2) gestational age range of 20–44 weeks inclusive, and 3) women who delivered both first and second consecutive singleton infants
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They were categorized into an exposed group consisting of those women who experienced a stillbirth delivery in the first pregnancy and a comparison group (those that had a live birth in the first pregnancy). These women were then followed up to their second pregnancy to determine pregnancy outcome. The main outcome of interest was occurrence of stillbirth in the subsequent pregnancy, which we defined as intrauterine fetal death at 20 weeks or more of gestation.
Information on maternal characteristics for each woman in the second pregnancy was considered to evaluate any differences in sociodemographic features (maternal age, marital status, educational status, cigarette smoking during pregnancy, body mass index [BMI] expressed as kg/m2, interpregnancy interval, and adequacy of prenatal care) between the 2 study arms. For live births in the first pregnancy (control group) we also determined whether these were preterm (< 37 weeks of gestation) or small for gestational age (SGA). SGA was defined as less than 10th percentile of birth weight for gestational age using population-based national reference curves for singletons.13 We categorized BMI into 4 groups: underweight (< 19.8), normal (19.8–26.0), overweight (26.1–29.0), and obese (> 29.0) based on a previous publication.14 Adequacy of prenatal care was assessed using the revised graduated index algorithm, which has been found to be more accurate than several others, especially in describing the level of prenatal care use among groups that are at high risk.15,16 This index assesses the adequacy of care based on the trimester that prenatal care began, number of visits, and the gestational age of the infant at birth. The interval between the first day of the last menstrual period (LMP) of the second pregnancy and the date of birth of the child in the first pregnancy was used to compute interpregnancy interval in days.
We performed crude frequency comparisons for the presence of common obstetric complications, namely, anemia, cardiac disease, insulin-dependent diabetes mellitus, other types of diabetes mellitus, chronic hypertension, preeclampsia, eclampsia, abruptio placenta, and placenta previa. We also constructed a composite variable indicating the presence of at least 1 of these conditions.
Stillbirth rates were computed by dividing the number of stillbirths by the sum of live birth and stillbirth and expressed as rate per 1,000 birth. The 
2 test was used to determine differences in sociodemographic characteristics and maternal pregnancy complications between the 2 groups. The Student t test was used when the outcome was continuous (eg, interpregnancy intervals). We used unconditional logistic regression analysis to model prior history of stillbirth as a determinant of subsequent stillbirth. Odds ratios were calculated before and after adjustment for maternal sociodemographic characteristics. In subsequent analysis, we further investigated the role of race as a risk factor for stillbirth recurrence. Adjusted odds ratios were estimated to determine the effect of racial subtypes (African Americans and whites) in the recurrence of stillbirth. All tests of hypothesis were 2-tailed, with a type 1 error rate fixed at 5%. SAS 9.1 (SAS Institute, Cary, NC) software was used to perform all analyses. This study was approved by the Institutional Review Board for Human subjects at the University of Alabama at Birmingham.
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RESULTS |
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Comparison of the frequency of maternal complications in the 2 study groups in their second pregnancy is given in Table 2. Women with a history of stillbirth in the first pregnancy had a 57% higher likelihood of having at least 1 complication during the second pregnancy as compared with the control group. When examined individually, complications such as insulin-dependent diabetes mellitus, chronic hypertension, preeclampsia, and placental abruption were more prevalent in the second pregnancy in those with a prior stillbirth in the first pregnancy. On the other hand, the occurrence of anemia was less common in the second pregnancy among women who had stillbirth in their first pregnancy. The prevalence of cardiac disease, other types of diabetes, eclampsia, and placenta previa was similar in the 2 groups.
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In total, there were 1,929 cases of stillbirth in the second pregnancy; 45 (2.3% of all cases) occurred in mothers with a history of stillbirth and 1,884 (97.7% of all cases) among those without such history. The rate (per 1,000) of stillbirth in the second pregnancy in women whose first delivery ended in a stillbirth was 22.7 compared with 4.7 for those who did not have a stillbirth in their first delivery. Stratification of the results according to the 2 main racial groups in the state showed a more pronounced disparity among African-American mothers (35.9/1,000 in those with a history of stillbirth compared with 7.6/1,000 in those with no prior history of stillbirth compared with 19.1/1,000 compared with 4.2/1,000 in whites).
Adjusted estimates for the relationship between prior experience of stillbirth and subsequent stillbirth recurrence are summarized in Table 3. Mothers with a history of stillbirth had a significantly greater likelihood for a stillbirth recurrence overall as well as within specific racial categories (African Americans and whites). The referent category in the analysis that yielded the results in model I (Table 3) comprised women with live birth in the first pregnancy, a group consisting of term, preterm and SGA live births. We further reanalyzed the data by restricting the referent category to term live births only in the first pregnancy. The results remained essentially unchanged; mothers with a previous history of stillbirth had a similar level of elevated risk for stillbirth recurrence when SGA, preterm, or both were excluded from the control group (Models II, III, and IV in Table 3, respectively).
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To determine whether race is a determinant of stillbirth recurrence we restricted our analysis to a cohort of women who experienced a stillbirth in the first pregnancy only. This comprised 1,567 whites (80.0%) and 390 African Americans (20.0%). These women were then followed up to their second pregnancy to determine the incidence of stillbirth (stillbirth recurrence). In African Americans, 14 cases (35.9/1,000) of stillbirth were registered in the second pregnancy as compared with 30 (19.1/1,000) in whites (P < .001). After adjusting for potential confounders, the risk of stillbirth recurrence in African Americans was almost 3 times as likely as in whites (odds ration 2.6, 95% confidence interval 1.2–5.7).
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DISCUSSION |
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Information on stillbirth recurrence is scanty, especially, at the population level. Although previous studies that addressed the issue seemed to have established a consensus that a woman with a history of stillbirth is at an elevated risk of losing her fetus in a subsequent pregnancy,3–4,17 a recent publication did not detect an association.18 The latter study was, however, severely underpowered because only 2 cases of stillbirth were observed in the group with a prior history of stillbirth.18 Our results are in consonance with the predominant reports in the literature.3–4,17,19
It is, however, pertinent to point out that our study examined stillbirth in general rather than unexplained stillbirth, for which no association has been reported with prior stillbirth.18 A persistent maternal condition (eg, diabetes) or a recurrent fetal condition (eg, congenital malformation) could explain the recurrence of stillbirth in a subsequent pregnancy. Our analysis did not explore the contribution of maternal and fetal conditions to stillbirth recurrence, because documentation of these on the birth certificate may not reach the level of accuracy needed to avoid biased information. Also, the causes of fetal death as recorded on birth certificates may not be accurate or useful in many instances, as reported by Kirby et al,20 and this limits our ability to offer biologic explanation for our findings.
The second hypothesis posits that race is a potential determinant of stillbirth recurrence. To our knowledge, analysis in this direction is lacking. We observed that when African-American and white women with a prior history of stillbirth were compared, stillbirth recurrence was almost tripled in African Americans. This indicates that within the general population racial variation exists regarding risk levels for stillbirth recurrence. This is important for a number of reasons. To attain the Healthy People 2010 objective21 of reducing racial disparities in health outcomes (including stillbirth), it is important to establish absolute as well as relative risk profiles of various groups within the population, a step that is critical in formulating effective prevention measures, including resource allocation. Nevertheless, a shortcoming in our analysis is the absence of information on other racial groups, especially the Hispanic population, a subgroup that now has the highest birth rate in the United States.22
A second reason that adds to the importance and timeliness of this analysis is the urgent need for a comprehensive research agenda to address the burden of stillbirth and its recurrence in the United States as expounded in previous publications.1 A third beneficial component of this investigation is its potential importance for counseling purposes. African-American pregnant women and health care providers need to be aware of the elevated absolute and relative risk for repeat stillbirth in African Americans.
A history of preterm or small for gestational age is a risk factor for subsequent stillbirth.22 Our results could have been confounded by the occurrence of small for gestational age or preterm delivery in the first pregnancy. Among women with live birth in the first pregnancy, SGA or preterm could have elevated their risk for subsequent stillbirth,23 leading to an underestimate of the relative risk for stillbirth recurrence. To determine the extent of this bias, we ran 3 additional models that excluded sequentially mothers with SGA, preterm, and any 1 of the 2 (Models II, III, and IV, respectively). The results did not change, implying that the association between prior stillbirth and subsequent stillbirth is so strong that the potential confounding effects of SGA or preterm may not influence the relationship.
A limitation in this study is the relatively few stillbirth cases in the subanalysis we conducted to elucidate the role of race as a determinant of subsequent stillbirth. Nonetheless, the fact that we did observe a difference is evidence that race may actually play an important role in stillbirth recurrence, and the association is strong.
A strength of this study is that it is population-based, which makes our findings generalizable. Another merit of this study is our ability to adjust for the effect of maternal BMI. Previous studies that have addressed the issue of stillbirth recurrence3–4,17–19 have failed to account for the influence of maternal BMI, an important cause of adverse pregnancy outcomes.
In summary, we found a history of stillbirth to be associated with a 5-fold increase for subsequent stillbirth. In addition, we found race to be a strong determinant of stillbirth recurrence. These findings will contribute to the enhancement of our current understanding of stillbirth recurrence, an area that has been poorly researched. The results could potentially be useful for counseling purposes.
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Footnotes |
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Supported through a Young Clinical Scientist Award to Dr. Hamisu Salihu by the Flight Attendant Medical Research Institute. The funding agency did not play any role in any aspect of the study. Dr. Ananth is partially supported through a grant (R01-HD038902) awarded to him from the National Institutes of Health.
Corresponding author: Hamisu Salihu, MD, PhD, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977; e-mail: hamisu.salihu{at}gmail.com.
doi:10.1097/01.AOG.0000196501.32272.44
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REFERENCES |
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2. Goldenberg RL, Kirby R, Culhane JF. Stillbirth: a review. J Matern Fetal Neonatal Med 2004;16:79–94.[Medline]
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