Poor outcome in first pregnancy may predict stillbirth in second one.

The odds that a second pregnancy will end in stillbirth are twice as high among women whose first pregnancy ends in the term delivery of an infant who is small for gestational age as among those whose first infant is born at term and is not undersized. (1) The differential is even greater (odds ratios, 3.4-5.0) if the undersized infant is also born moderately or very preterm. In addition, women whose first pregnancy ends in stillbirth have elevated odds of having the same outcome in their second pregnancy (2.5).

To assess relationships between adverse outcomes of a first pregnancy and the likelihood of stillbirth in a second pregnancy, researchers analyzed data from the Swedish Medical Birth Register, which includes virtually all births in the country, for the years 1983-1997. Analyses were restricted to women who delivered first and second consecutive singleton infants. The researchers determined maternal social and demographic characteristics and complications of pregnancies from the birth register and linked databases. Pregnancy outcomes were classified as live births or stillbirths (fetal death at 28 weeks' gestation or later). Live births were further classified as occurring at term (37 or more weeks of completed pregnancy), moderately preterm (32-36 weeks) or very preterm (fewer than 32 weeks). An infant having a birth weight that was more than two standard deviations below average for gestational age was defined as being small for gestational age.

Overall, the 410,021 women included in the analyses had 2.6 stillbirths per 1,000 births in their second pregnancy. The rate was lowest among women whose first pregnancy ended in the term birth of an infant who was not undersized (2.4 per 1,000) and highest among those whose first infant was both small for gestational age and very preterm (19.0 per 1,000). In unadjusted analyses using the former women as the reference group, the odds of stillbirth were significantly elevated for women whose first infant was not undersized but was very preterm, for women whose first infant was small for gestational age, regardless of the duration of pregnancy, and for women whose first infant was stillborn.

Additionally, unadjusted analyses suggested that several complications of pregnancy and maternal characteristics were related to the likelihood of stillbirth. The odds were increased among women who had bleeding or hypertension during their second pregnancy, were overweight or obese (as measured by body mass index), were 35 or older, smoked, had been born in a non-Nordic country, or had had their first two pregnancies within a short interval (three months or less) or spaced very far apart (72 months or more).

In adjusted analyses, all of these characteristics except maternal body mass index, plus several other social and demographic factors, were controlled for; again, women whose first pregnancy ended in the term birth of an infant who was not small for gestational age constituted the reference group. In these calculations, the odds of stillbirth in the second pregnancy were elevated for women whose first pregnancy ended in the preterm birth of an infant who was not undersized (odds ratio, 2.0), but the association was no longer statistically significant after further adjustment for maternal body mass index and height. The odds were raised among women whose first infant was small for gestational age and born at term (2.1), and were sharply elevated for women whose first infant was undersized and either moderately preterm (3.4) or very preterm (5.0). In addition, women whose first infant was stillborn were at increased risk of having their second pregnancy end in a stillbirth (2.5). These associations persisted after further adjustment for maternal body mass index and height.

The researchers speculate that some of the same factors affecting fetal growth in a womman's first pregnancy may affect fetal survival in her second pregnancy, and they note that the findings highlight the "central role of fetal growth restriction" in the etiology of stillbirth. While commenting that many of the odds ratios from their analyses are large, they observe that "the rates and absolute risks of stillbirth during a second pregnancy are still quite low, and the overwhelming majority of women whose first infant was small for gestational age delivered liveborn second infants." They conclude that although some fetuses at increased risk for stillbirth can now be identified, the optimal intervention if such a fetus is identified very preterm remains uncertain.

REFERENCE

(1.) Surkan PJ et al., Previous preterm and small-for-gestational-age births and the subsequent risk of stillbirth, New England Journal of Medicine, 2004, 350(8): 777-785.