Fetal cerebellar growth and Sylvian fissure maturation: International standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.
Rodriguez-Sibaja MJ., Villar J., Ohuma EO., Napolitano R., Heyl S., Carvalho M., Jaffer YA., Noble JA., Oberto M., Purwar M., Pang R., Ismail LC., Lambert A., Gravett MG., Salomon LJ., Drukker L., Barros FC., Kennedy SH., Bhutta ZA., Papageorghiou AT.
OBJECTIVE: To construct international ultrasound-based standards for cerebellar growth and Sylvian fissure maturation. METHODS: Healthy, well-nourished pregnant women, enrolled at <14 weeks of gestation in the Fetal Growth Longitudinal Study (FGLS) of INTERGROWTH-21st , an international multicenter, population-based project, underwent 3D serial fetal ultrasound scans every 5±1 weeks until delivery in study sites located in Brazil, India, Italy, Kenya and the UK. We measured the trans-cerebellar diameter and assessed Sylvian fissure maturation using 2D images extracted from the available 3D fetal head volumes acquired. For each Sylvian fissure maturation score (left and right), we calculated the mean gestational age and 95% CI. We assessed goodness of fit of the resultant model and the possibility of pooling data from the five sites using variance component analysis and standardized site differences. We modelled trans-cerebellar diameter and Sylvian fissure maturation using fractional polynomial regression and fitted centiles. RESULTS: Of those children in the original FGLS cohort who had a developmental assessment at 2 years of age, 1,130 also had an available 3D fetal head volume. The socio-demographic characteristics and pregnancy/perinatal outcomes of the study sample confirmed the health and low-risk status of the population studied. In total, 3,016 and 2,359 individual volumes were available for trans-cerebellar diameter and Sylvian fissure analysis, respectively. Variance component analysis and standardized site differences showed that the five study populations were sufficiently similar on the basis of predefined criteria for the data to be pooled to produce international standards. A second-degree fractional polynomial provided the best fit for modelling trans-cerebellar diameter; we then estimated gestational age-specific 3rd , 50th and 97th smoothed centiles. Goodness of fit comparing empirical centiles to smoothed centile curves showed good agreement. The Sylvian fissure increased in maturation with advancing gestation with complete overlap of the mean gestational age and 95% CI between the sexes for each development score. No differences in maturation between the right and left hemispheres were observed. CONCLUSION: We present here, for the first time, international standards for fetal cerebellar growth and Sylvian fissure maturation throughout pregnancy based on a healthy fetal population that exhibited adequate growth and development at 2 years of age. This article is protected by copyright. All rights reserved.