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-21^st 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 16^th, 2021). We included full-text articles investigating the ability of INTERGROWTH-21^st 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 <10^th 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.

本研究旨在系统评价并评估采用INTERGROWTH-21st估算胎儿体重（estimated fetal weight, EFW）标准，预测孕产妇、胎儿及新生儿不良结局的相关文献中的偏倚风险。本研究于2014年至2021年4月16日末次检索期间，借助引文检索工具与关键词组合（intergrowth AND (standard OR reference OR formula OR model OR curve)），在Scopus、Web of Science、Medline、Embase、Lilacs、Scielo及Google Scholar共7个电子数据库中开展文献检索。本研究纳入全文发表的文献，需满足以下条件：探讨单胎妊娠且分娩无先天性异常新生儿的孕妇，使用INTERGROWTH-21st EFW标准预测其孕产妇、胎儿或新生儿不良结局的能力。本研究已在PROSPERO平台注册，注册号为CRD42020115462。采用基于CHARMS检查表定制的、包含9个领域的偏倚风险评估工具开展偏倚评价。针对2项及以上方法学同质研究所报告的结局指标，采用相对危险度（relative risk, RR [95%CI]）及汇总受试者工作特征曲线（summary receiver operating characteristic, SROC）开展Meta分析。最终纳入16项研究，共评估15种不同的结局指标。在2个领域存在较高偏倚风险（≥50%的研究具有高偏倚风险）：评估盲法（占比81.3%）与校准评估（占比93.8%）。综合所有纳入研究的结局指标，95%的研究结果显示特异性高于73.0%，但敏感性均低于64.1%。合并分析结果表明，与分类为高于或等于第10百分位的胎儿相比，分类为低于第10百分位的胎儿发生新生儿小于胎龄儿（small for gestational age, SGA，相对危险度为6.71 [5.51–8.17]）、5分钟Apgar评分<7分（2.17 [1.48–3.18]）及新生儿重症监护病房（neonatal intensive care unit, NICU）收治（2.22 [1.76–2.79]）的相对危险度更高。本研究存在局限性：未开展异质性探讨或发表偏倚分析，且单一结局指标的纳入研究数量均未超过5项。INTERGROWTH-21st EFW标准对妊娠不良事件的预测敏感性较低、特异性较高。将胎儿分类为低于第10百分位，可识别出发生孕产妇、胎儿及新生儿不良结局的高危人群，尤其是新生儿小于胎龄儿、5分钟Apgar评分<7分及新生儿重症监护病房收治的情况。未来研究应采用结局评估盲法、使用连续数据开展校准分析，并评估其他截断值。