DOI: 10.1111/j.1471-0528.2011.03137.x www.bjog.org
Infant mortality and subsequent risk of stillbirth: a retrospective cohort study EM August,a HM Salihu,b,c H Weldeselasse,b BJ Biroscak,a AK Mbah,b AP Aliod a Department of Community and Family Health, College of Public Health b Department of Epidemiology and Biostatistics, College of Public Health c Department of Obstetrics and Gynecology, College of Medicine, University of South Florida, Tampa, FL, USA d Department of Community and Preventive Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA Correspondence: Prof H Salihu, Department of Epidemiology & Biostatistics, College of Public Health, University of South Florida, 13201 Bruce B. Downs Blvd, MDC56, Tampa, FL 33612, USA. Email [email protected]
Accepted 25 July 2011. Published Online 21 September 2011.
Objective To examine the association between infant mortality
Main outcome measures Exposure was defined as infant mortality
in a first pregnancy and risk for stillbirth in a second pregnancy.
in the first pregnancy, and the outcome was defined as stillbirth in the second pregnancy.
Design Population-based, retrospective cohort study.
Results Women with prior infant deaths were about three times as likely to experience stillbirth in their subsequent pregnancy (AHR 2.91; 95% CI 2.02–4.18). White women with a previous infant death were nearly twice as likely to experience a subsequent stillbirth, compared with white women with a surviving infant (AHR 1.96; 95% CI 1.13–3.39). Black women with a previous infant death were more than four times as likely to experience subsequent stillbirth, compared with black women with a surviving infant (AHR 4.28; 95% CI 2.61–6.99).
Setting Maternally linked cohort data files for the state of
Missouri. Population Women who had two singleton pregnancies in Missouri during the period 1989–2005 (n = 320 350). Methods Women whose first pregnancy resulted in infant death
were compared with those whose infant from the first pregnancy survived the first year of life. The Kaplan–Meier product limit estimator was employed to compare probabilities for stillbirth in the second pregnancy between both groups of women. Adjusted hazard ratios (AHRs) and 95% confidence intervals (95% CIs) were generated to assess the association between infant mortality in the first pregnancy and stillbirth in the second pregnancy.
Conclusions Previous infant mortality results in an elevated risk
for subsequent stillbirth, with the most profound increase observed among black women. Interconception care should consider prior childbearing experiences to avert subsequent fetal loss. Keywords Health disparity, infant mortality, pregnancy, stillbirth.
Please cite this paper as: August E, Salihu H, Weldeselasse H, Biroscak B, Mbah A, Alio A. Infant mortality and subsequent risk of stillbirth: a retrospective cohort study. BJOG 2011; DOI: 10.1111/j.1471-0528.2011.03137.x.
Introduction Despite reports of an estimated 3.2–3.3 million stillbirths annually worldwide,1–4 stillbirth is relatively absent from global health policy agendas, including the United Nations Millennium Development Goals.5,6 Inconsistent definitions for stillbirth abound, which, along with other data limitations, particularly in developing countries (e.g. fragmented vital records systems, a prevalence of home births, and a lack of political will),2,3,6,7 can hinder efforts to describe, understand, and subsequently prevent the occurrence of stillbirth. Not surprisingly, most interventions to prevent stillbirth also require additional research to improve the quality of evidence.8,9 Many newborn infants that survive the neonatal period are not out of the proverbial woods. Infant mortality, defined
as the death of a child within the first year of life,10 accounts for an estimated 5.75 million deaths worldwide, or 42 infant deaths per 1000 live births.11 The United Nations Millennium Development Goals call for a reduction by two-thirds of the mortality rate of children under the age of 5 years by the year 2015;5 however, it excludes an explicit goal for infant mortality. Preventive efforts must be directed at preterm delivery and low birthweight, which are the main precursors of infant mortality.12 Moreover, racial/ethnic disparities in infant mortality highlight the need to consider more distal factors, such as secondary effects of low socio-economic status, suboptimal social support, and unhealthy neighborhoods.13 Just as the first year of life can be a precarious time period for many infants, pregnancy following a fetal loss can
ª 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2011 RCOG
August et al.
carry with it a heightened risk for subsequent adverse events, such as preterm delivery,14,15 low birthweight,16 and stillbirth recurrence.17–19 A related association that has largely gone unexamined to date is the subsequent risk of stillbirth after the death of a previous infant. Despite the relatively frequent occurrence of both stillbirth and infant mortality in the USA, little is known regarding the association between the two. A recent study conducted in one US county attempted to examine the association between previous infant death and subsequent fetal mortality, but had an insufficient sample size.20 To address this gap in the literature, we used a population-based data set to examine the association between infant mortality and stillbirth during a subsequent pregnancy. Furthermore, we investigated whether racial disparities exist within this association.
Methods We used the Missouri maternally linked cohort data files for the period 1989–2005 (inclusive), with a total population of 1 035 547 births. This data set links siblings to their biological mothers using unique identifiers. The methods and algorithm used in linking birth certificate data with sibling relationships and the process of validation have been described in detail previously.21 The Missouri vital record system is a reliable record system that has been adopted as the gold standard to validate US national data sets that involve matching and linking procedures.22 The Missouri maternally linked cohort data set contains information on both live births and fetal deaths for each sibling, and provides a platform for a longitudinal study of birth outcomes for each pregnancy. The main exposure of interest in the present study was infant mortality (defined as the death of the infant within the period from day 0 to 364) associated with the first pregnancy. We also considered neonatal death (death of a newborn within the first 28 days of life) and post-neonatal death (death of the infant within the period from day 29 to 364). Our primary outcome was stillbirth (in utero fetal death occurring after at least 20 weeks of gestation) associated with the second pregnancy. As our objective was to examine the association between infant mortality and stillbirth in the first and second pregnancies, respectively, we selected two consecutive births from the same mother with a gestational age range of 20–44 weeks. After applying further exclusion criteria (Figure 1), we retained a total of 640 700 births (320 350 from each pregnancy) for this analysis. We compared mothers with previous infant death versus those who had infants who survived their first year with respect to the following maternal characteristics at the time of the second delivery: race, age, marital status, educational level, cigarette smoking during pregnancy, body mass
index, interpregnancy interval, and adequacy of prenatal care. Maternal race was grouped into three categories: white, black, and other. Maternal age was dichotomized as women who were of advanced age (i.e. 35 years old or older) or were younger than 35 years old at the time of the second delivery. Maternal marital status was grouped as either married or unmarried, with all women who were single, divorced, or widowed being classified as unmarried. Maternal educational level was categorized as women with at least a high school diploma or its equivalent (‡12 years of education) and those without a high school diploma ( 44 weeks [47 477 (4.6%)] = 778 441
Eliminate multiple gestations [41 191 (4.0%)] = 825 918
Eliminate cases with no siblings [130 781(12.6%)] = 647 660
Eliminate cases that are not sibling pairs [2 177 (0.21%) = 645 483
Eliminate cases with fetal death in the second pregnancy [1 940 (0.19%)] = 643 543
Eliminate cases with stillbirth in the first pregnancy [1 568 (0.15%)] = 641 975
Eliminate cases with implausible interpregnancy interval (