Risk of stillbirth, preterm delivery and fetal growth restriction following exposure in previous birth: systematic review and meta-analysis

Background: Little is known about the risk of non-recurrent adverse birth outcomes. Objectives: To evaluate the risk of stillbirth, preterm birth (PTB), and small for gestational age (SGA) as a proxy for fetal growth restriction (FGR) following exposure to one or more of these factors in a previous birth. Search strategy: We searched MEDLINE, EMBASE, Maternity and Infant Care, and Global Health from inception to 30 November 2016. Selection criteria: Studies were included if they investigated the association between stillbirth, PTB, or SGA (as a proxy for FGR) in two subsequent births. Data collection and analysis: Meta-analysis and pooled association presented as odds ratios (ORs) and adjusted odds ratios (aORs). Main results: Of the 3399 studies identified, 17 met the inclusion criteria. A PTB or SGA (as a proxy for FGR) infant increased the risk of subsequent stillbirth ((pooled OR 1.70; 95% confidence interval, 95% CI, 1.34–2.16) and (pooled OR 1.98; 95% CI 1.70–2.31), respectively). A combination of exposures, such as a preterm SGA (as a proxy for FGR) birth, doubled the risk of subsequent stillbirth (pooled OR 4.47; 95% CI 2.58–7.76). The risk of stillbirth also varied with prematurity, increasing three-fold following PTB <34 weeks of gestation (pooled OR 2.98; 95% CI 2.05–4.34) and six-fold following preterm SGA (as a proxy for FGR) <34 weeks of gestation (pooled OR 6.00; 95% CI 3.43–10.49). A previous stillbirth increased the risk of PTB (pooled OR 2.82; 95% CI 2.31–3.45), and subsequent SGA (as a proxy for FGR) (pooled OR 1.39; 95% CI 1.10–1.76). Conclusion: The risk of stillbirth, PTB, or SGA (as a proxy for FGR) was moderately elevated in women who previously experienced a single exposure, but increased between two- and three-fold when two prior adverse outcomes were combined. Clinical guidelines should consider the inter-relationship of stillbirth, PTB, and SGA, and that each condition is an independent risk factor for the other conditions