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

Abstract

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 standards^5,6, and growth and neurodevelopment up to 2 years of age^7,8. 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.

Fig. 1. Fetal cranial growth trajectories in the INTERBIO-21st Study.

Fig. 2. Trajectories of head circumference z-scores from prenatal measurements through 2 years of age, stratified by fetal cranial growth trajectories

Fetal measures are from the ultrasound visit closest to 27 weeks’ gestation. Error bars represent the 95% confidence intervals of the means.

Fig. 3. Changes at 2 years of age associated with fetal cranial growth trajectories in the INTERBIO-21st Study

Child neurodevelopmental outcomes. For cognitive, language, motor and positive behavior outcomes, higher scores represent better outcomes; for negative behavior, attentional problems and emotional reactivity, higher scores represent worse outcomes. b, Child vision. Relative risks > 1 refer to an increased risk of poor visual performance; relative risks < 1 refer to a reduced risk of problems. c, Child growth: change in z-scores. Median growth tracking trajectory is the reference group. Models include maternal education and age at birth, preterm birth and smoking in pregnancy, and child sex and age at assessment.