We carried out a population-based retrospective cohort study of all twin births in the United States for the period of 1995-1997, using the matched multiple birth file created by the Centers for Disease Control and Prevention. This database was created by linking the twin birth file and the corresponding death report file. The linkage was successful in 98.8% of the records. Fetal death was defined as stillbirth weighing 350 g or more, or if weight was unknown, 20 completed gestation weeks or more. Available study variables in the database include sociodemographic information of the parents, maternal lifestyle factors, such as smoking and alcohol consumption, during pregnancy, obstetric history, complications of the pregnancy, labor and delivery, and birthweight, gestational age, and other infant outcome variables. Only matched twin sets were included in the current study, with individual twin as the unit of analysis.
The outcomes (dependent variables) of the study were fetal and infant deaths. Fetal death was further divided into early fetal death (20-27 gestation weeks) and late fetal death (>28 gestation weeks); and infant death was further divided into early neonatal death (0-6 days), late neonatal death (7-27 days), and postneonatal death (28-364 days).
A conceptual framework for perinatal surveillance that focuses on preventable feto-infant mortality was described by Dr. Brian McCarthy, Centers for Disease Control and Prevention, Atlanta, GA. To this framework, factors affecting maternal health, maternal care, neonatal intensive care, or infant environment may have different effects on late fetal, neonatal, and postneonatal deaths. Such effects may be modified by birthweight. Separating feto-infant mortality into different components may help to suggest opportunity gaps among population subgroups in terms of maternal health and the quality of maternal and newborn care, and infant environment. For example, if most of the excessive mortality among blacks occurred in postneonatal period, effort should be made to improve environment (e.g., injury prevention and control) for black infants.
The independent variable (exposure) of the study was the parental race. Because most of the parents were either white or black, we excluded infants whose parents were other races or unknown. The eligible study subjects were divided into four groups according to parental race: both parents whites (W-W), both parents blacks (B-B), father black and mother white (FB-MW), and father white and mother black (FW-MB).
We also considered and controlled for potential confounding factors, including parents’ age, maternal education, cigarette smoking during pregnancy, prenatal care service, fetal growth restriction (FGR), preterm birth, and very low birthweight (VLBW). The prenatal care service was defined as adequate,
intermediate, and inadequate according to the time of prenatal care visit initiation and the number of prenatal visits using the criteria developed by Ressner. FGR was defined as birthweight-for-gestation-al-age z score less than 10th percentiles. The birth-weight-for-gestational-age z score was calculated using the following formula:
Z-score = (observed birthweight – mean of birthweight) / SD
where mean and SD was based on all infants in the database, stratified by gender and gestational week.
Preterm birth was defined as gestational age less than 32 complete weeks. Gestational age in the database was estimated by the interval between the first day of last menstrual period (LMP) and the date of delivery. If the date of LMP was not recorded or if the calculated gestation weeks fell beyond the duration considered biologically plausible, gestational age estimated by physician was used. VLBW was defined as birthweight less than 1,500 g.
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We first described the distribution of baseline characteristics and then compared the fetal and infant mortality rates among the four study groups. To assess the independent effect of parental race, we calculated the fetal and infant mortality rate ratio among the B-B, FB-MW, and FW-MB groups compared with the W-W group by a step-by-step “risk-free” analysis. Step-by-step “risk-free” analysis makes it possible to assess whether and to what extent the observed association between parental race and fetal and infant mortality is attributable to the differences in risk factors or combination of risk factors among the study groups. In a previous study, we have found that “riskfree” is a more effective and efficient analytic approach to reveal the differences in birthweight distribution between Chinese and white infants than conventional analysis, such as regression models. We used six “risk-free” steps: step 1 excluded subjects with parents’ age less than 20 and maternal education less than 12 years; step 2 excluded subjects with mother smoked cigarette during pregnancy, in addition to subjects excluded in step 1; step 3 excluded subjects with inadequate perinatal care service, in addition to subjects excluded in step 2; step 4 excluded subjects with FGR, in addition to subjects excluded in step 3; step 5 excluded subjects with preterm birth, in addition to subjects excluded in step 4; and step 6 excluded subjects with VLBW, in addition to subjects excluded in step 5.