Quantifying prenatal and postnatal mortality in extreme early onset fetal growth restriction: A systematic review and incidence analysis.

Background and Objective: Extreme early-onset fetal growth restriction (EE-FGR) is associated with significant perinatal morbidity and mortality. As short- and long-term prognoses are influenced by both gestational age and severity of FGR, quantifying risk is inherently challenging. We hypothesized that a meta-analysis would provide quantifiable estimates of perinatal outcomes in pregnancies complicated by EE-FGR. Methods: We searched PubMed, Scopus, Embase, and Web of Science databases for relevant studies published from inception to March 2024. We included all original studies involving singleton pregnancies with estimated fetal weights (EFWs) or abdominal circumferences < third centile or EFWs < 600 g, between 20 + 0 and 26 + 6 weeks of gestation. Studies were limited to fetuses with no known chromosomal, genetic, or major structural abnormalities. The National Institute of Health Quality Assessment Tool was utilized for the risk of bias assessment. Incidence meta-analyses were performed with proportions (percentages) calculated for each outcome using a random-effects model. Results: Five cohort studies (three prospective and two retrospective), comprising a total of 614 pregnancies, were included in the review. Two studies had overlapping populations; in such cases, the study containing the most relevant variables was selected for analysis. Four studies demonstrated good quality, and one was of fair quality. Pregnancy loss occurred at a rate of 39% (95% confidence interval [CI]: 29%-49%). Among live births, neonatal death was observed in 14% (95% CI: 4%-24%). Preterm birth (<37 weeks) was reported in 68% of cases (95% CI: 40%-96%), with very preterm birth (<32 weeks) accounting for 61% (95% CI: 34%-88%) of these, and extreme preterm birth (<28 weeks) comprising 25%. Additionally, 29% (95% CI: 20%-39%) of pregnancies were complicated by preeclampsia and/or hemolysis, elevated liver enzyme levels, and low platelet levels (HELLP) syndrome, with high heterogeneity ( Conclusion: Our meta-analyses quantitated the incidence of adverse fetal, neonatal, and maternal outcomes with EE-FGR, with the risk of pregnancy loss or neonatal death approaching nearly 50%, and among survivors, more than two thirds were born preterm. These findings provide valuable data for counseling families facing EE-FGR, though high heterogeneity highlights the need for further research. Trial Registration: PROSPERO database [CRD42019120930].