Fetal cranial growth trajectories are associated with growth and neurodevelopment at 2 years of age: INTERBIO-21st Fetal Study

José Villar, Robert B. Gunier, Chrystelle O.O. Tshivuila-Matala, Stephen A. Rauch, Francois Nosten, Roseline Ochieng, María C. Restrepo-Méndez, Rose McGready, Fernando C. Barros, Michelle Fernandes, Verena I. Carrara, Cesar G. Victora, Shama Munim, Rachel Craik, Hellen C. Barsosio, Maria Carvalho, James A. Berkley, Leila Cheikh Ismail, Shane A. Norris, Eric O. OhumaAlan Stein, Ann Lambert, Adele Winsey, Ricardo Uauy, Brenda Eskenazi, Zulfiqar A. Bhutta, Aris T. Papageorghiou, Stephen H. Kennedy

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections)1 and preventive interventions (for example, multiple-micronutrient supplementation)2 that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood3. In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites worldwide4, we studied the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks’ gestation, against international standards5,6, and growth and neurodevelopment up to 2 years of age7,8. We identified five trajectories associated with specific neurodevelopmental, behavioral, visual and growth outcomes, independent of fetal abdominal growth, postnatal morbidity and anthropometric measures at birth and age 2. The trajectories, which changed within a 20–25-week gestational age window, were associated with brain development at 2 years of age according to a mirror (positive/negative) pattern, mostly focused on maturation of cognitive, language and visual skills. Further research should explore the potential for preventive interventions in pregnancy to improve infant neurodevelopmental outcomes before the critical window of opportunity that precedes the divergence of growth at 20–25 weeks’ gestation.

Original languageEnglish
Pages (from-to)647-652
Number of pages6
JournalNature Medicine
Issue number4
Publication statusPublished - Apr 2021
Externally publishedYes


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