The clinical performance and population health impact of birth weight-for-gestational age indices with regard to adverse neonatal outcomes in term infants

Background Despite the recent creation of several birth weight-for-gestational age references and standards, none has proven superior. We identified birth weight-for-gestational age cut-offs, and corresponding United States population-based, Intergrowth 21st and World Health Organization centiles associated with higher risks of adverse neonatal outcomes, and evaluated their ability to predict serious neonatal morbidity and neonatal mortality (SNMM). Methods and findings The study population comprised singleton live births at 37-41 weeks’ gestation in the United States, 2003-2017. Birth weight-specific SNMM, which included 5-minute Apgar score<4, neonatal seizures, assisted ventilation and neonatal death, was modeled by gestational week using penalized B-splines. We estimated the birth weights at which SNMM odds was minimized (and higher by 10%, 50% and 100%), and identified the corresponding population, Intergrowth 21st and World Health Organization (WHO) centiles. We then evaluated the individual- and population-level performance of these cut-offs for predicting SNMM. The study included 40,179,663 live births at 37-41 weeks’ gestation and 991,486 SNMM cases. Among female singletons at 39 weeks’ gestation, SNMM odds was lowest at 3,203 g birth weight (population, Intergrowth and WHO centiles 40, 52 and 46, respectively), and 10% higher at 2,835 g and 3,685 g (population centiles 11th and 82nd, Intergrowth centiles 17th and 88th and WHO centiles 15th and 85th). SNMM odds were 50% higher at 2,495 g and 4,224 g and 100% higher at 2,268 g and 4,593 g. Birth weight cut-offs were poor predictors of SNMM. For example, the birth weight cut-off associated with 10% higher odds of SNMM among female singletons at 39 weeks’ gestation resulted in a sensitivity of 12.5%, specificity of 89.4% and population attributable fraction of 2.1%, while the cut-off associated with 50% higher odds resulted in a sensitivity of 2.9%, specificity of 98.4% and population attributable fraction of 1.3%. Conclusions Birth weight-for-gestational age cut-offs and centiles perform poorly when used to predict adverse neonatal outcomes in individual infants, and the population impact associated with these cut-offs is also small. Funding Canadian Institutes of Health Research (MOP-67125 and PJT153439). Why was this study done What did the researchers do and find? What do these findings mean? ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Canadian Institutes of Health Research (grant MOP-67125 and PJT 153439). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data source: Birth-infant death files of the National Center for Health Statistics, CDC, USA. Data are publicly available at I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data used in this study are available from the National Center for Health Statistics, Centers for Disease Control and Prevention () * AGA : Appropriate for gestational age LGA : Large for gestational age PAF : Population attributable fraction SGA : Small for gestational age SNMM : Serious neonatal morbidity or neonatal mortality