Risk of Stillbirth, Preterm Delivery, and Fetal Growth Restriction Following Exposure in a Previous Birth: Systematic Review and Meta-analysis

The leading cause of infant morbidity and mortality are stillbirth, preterm birth (PTB), and small for gestational age (SGA), which can occur as a result of fetal growth restriction (FGR). Contemporary literature shows a significant increase in the risk of stillbirth, PTB, or SGA after its presentation in a prior pregnancy. Traditionally, these adverse events have been studied as individual entities; however, each of these outcomesmight indicate predisposition to subsequent other adverse perinatal outcomes. This systematic review and meta-analysis aimed to determine the nonrecurrent risk of stillbirth, PTB, and SGA after exposure to one or more of these complications in a previous pregnancy. Data were collected from eligible studies through MEDLINE, EMBASE, Maternity and Infant Care, and Global Health through Ovid from inception through November 30, 2016. Studies were eligible if reporting nonrecurrent risk of adverse birth outcomes after exposure to one or more of these in a prior pregnancy and singleton births of gestation greater than 20 weeks. Adverse birth outcomes analyzed were stillbirth, defined as fetal death past 20 weeks of gestation; PTB, defined as birth less than 37 weeks of gestation; and SGA, defined as infant birth weight below the tenth percentile. A total of 17 studies fulfilled the eligibility criteria. The data from the studies included pregnancies from 1967 through 2013. The pooled odds ratio (OR) of stillbirth was 1.70 (95% confidence interval [ CI], 1.34-2.16) after a previous PTB, and 1.98 (95% CI, 1.70-2.31) after a previous SGA birth. If a previous SGA birth was also preterm, the risk for stillbirth was higher (pooled OR, 4.47; 95% CI, 2.58-7.76). Variation in prematurity affected the risk of stillbirth, with a 3-fold and 6-fold increase in risk for stillbirth after PTB less than 34 weeks (pooled OR, 2.98; 95% CI, 2.05-4.34) and preterm SGA less than 34 weeks (pooled OR, 6.00; 95% CI, 3.43-10.49). The OR for SGA stillbirth after PTB was 2.91 (95% CI, 2.05-4.31) and increased 9-fold after PTB less than 34 weeks (OR, 8.90; 95% CI, 5.08-15.62). The pooled OR of PTB after stillbirth was 2.82 (95% CI, 2.31-3.45) and after SGAwas 2.7 (95% CI, 2.0-3.7). The pooledOR of SGA after stillbirth was 1.39 (95% CI, 1.10-1.76) and after PTB was 1.66 (95% CI, 1.53-1.81). The OR of SGA stillbirth after an SGA birth was found to be 12.63 (95% CI, 7.67-20.79), and this doubled if the prior SGA birth was less than 34 weeks of gestation (OR, 24.95; 95% CI, 12.73-48.91). These results demonstrate the interrelation between the studied birth outcomes by showing a significant increase in the risk of stillbirth, PTB, and SGA in women who previously experienced a single adverse birth outcome. The relative risk was compounded when multiple exposures were combined. It is critical for providers to be aware of not only elevated risk of recurrence after one of these exposures, but of all the risks for women with a history of adverse birth outcomes.