First pregnancy as a window of opportunity to identify future risk for perinatal mortality

Objective
Perinatal mortality occurs in 6.3 million fetuses and newborns/year, and it emerges as a prominent component of early childhood mortality, therefore the World Health Organization set a goal to reduce perinatal mortality. We aimed to identify risk factors in first pregnancy for perinatal mortality in the subsequent pregnancy.

Study Design
A retrospective population-based nested case-control study was conducted, including all women with two first singleton consecutive deliveries. Women with perinatal mortality in the first pregnancy were excluded. Cases were defined as women with perinatal mortality in second pregnancy, and they were compared to the controls, defined as women delivering a live birth. Characteristics and complications of the first pregnancy were compared between cases and controls, and multivariable logistic models were used to study the association between pregnancy complications in the first pregnancy and perinatal mortality in the subsequent pregnancy, while adjusting for confounders.

Results
A total of 43,043 women were included in the study, 0.9% of second pregnancies ended with perinatal mortality (n=385, i.e., Cases). Cases, as compared to controls (live births), were younger, with shorter inter-pregnancy interval, and were more likely to have the following complications in their first pregnancy (Table): small for gestational age (12.5% vs. 8.8%), preterm delivery (17.7% vs. 7.8%) and congenital or chromosomal malformations (9.6% vs. 5.9%; Table). In the multivariable model, which adjusted for maternal age and inter-pregnancy interval, either one of these first pregnancy complications were associated with an increased risk for preterm delivery (adjusted OR=1.73; 95% CI 1.37-2.14, p< 0.001), and the risk was greater for additional complication (adjusted OR for ≥2 risk factors= 3.54; 95% CI 2.28- 5.52, p< 0.001 (Graph).

Conclusion
Complications in first pregnancy ending with a live birth, are associated with an increased risk for perinatal mortality, and may serve as a window of opportunity to identify pregnancies at risk for future perinatal mortality.