Estimated fetal weight standards of the INTERGROWTH-21^st project for the prediction of adverse outcomes: a systematic review with meta-analysis

To systematically review and assess the risk of bias in the literature evaluating the performance of INTERGROWTH-21st estimated fetal weight (EFW) standards to predict maternal, fetal and neonatal adverse outcomes.Searches were performed in seven electronic databases (Scopus, Web of Science, Medline, Embase, Lilacs, Scielo and Google Scholar) using citation tools and keywords (intergrowth AND (standard OR reference OR formula OR model OR curve); all from 2014 to the last search on April 16th, 2021). We included full-text articles investigating the ability of INTERGROWTH-21st EFW standards to predict maternal, fetal or neonatal adverse outcomes in women with a singleton pregnancy who gave birth to infants with no congenital abnormalities. The study was registered on PROSPERO under the number CRD42020115462. Risk of bias was assessed with a customized instrument based on the CHARMS checklist and composed of 9 domains. Meta-analysis was performed using relative risk (RR [95%CI]) and summary ROC curves on outcomes reported by two or more methodologically homogeneous studies.Sixteen studies evaluating fifteen different outcomes were selected. The risk of bias was high (>50% of studies with high risk) for two domains: blindness of assessment (81.3%) and calibration assessment (93.8%). Considering all the outcomes investigated, for 95% of the results, the specificity was above 73.0%, but the sensitivity was below 64.1%. Pooled results demonstrated a higher RR of neonatal small for gestational age (6.71 [5.51-8.17]), Apgar <7 at 5 min (2.17 [1.48-3.18]), and neonatal intensive care unit admission (2.22 [1.76-2.79]) for fetuses classified <10th percentile when compared to those classified above this limit. The limitation of the study is the absence of heterogeneity exploration or publication bias investigation, whereas no outcomes were evaluated by more than five studies.The IG-21 EFW standard has low sensitivity and high specificity for adverse events of pregnancy. Classification <10th percentile identifies a high-risk group for developing maternal, fetal and neonatal adverse outcomes, especially neonatal small for gestational age, Apgar <7 at 5 min, and neonatal intensive care unit admission. Future studies should include blind assessment of outcomes, perform calibration analysis with continuous data, and evaluate alternative cutoff points.