Abstract
To construct international ultrasound-based standards for fetal cerebellar growth and Sylvian fissure maturation. Healthy, well nourished pregnant women, enrolled at < 14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of INTERGROWTH-21st , an international multicenter, population-based project, underwent serial three-dimensional (3D) fetal ultrasound scans every 5 ± 1 weeks until delivery in study sites located in Brazil, India, Italy, Kenya and the UK. In the present analysis, only those fetuses that underwent developmental assessment at 2 years of age were included. We measured the transcerebellar diameter and assessed Sylvian fissure maturation using two-dimensional ultrasound images extracted from available 3D fetal head volumes. The appropriateness of pooling data from the five sites was assessed using variance component analysis and standardized site differences. For each Sylvian fissure maturation score (left or right side), mean gestational age and 95% CI were calculated. Transcerebellar diameter was modeled using fractional polynomial regression, and goodness of fit was assessed. Of those children in the original FGLS cohort who had developmental assessment at 2 years of age, 1130 also had an available 3D ultrasound fetal head volume. The sociodemographic characteristics and pregnancy/perinatal outcomes of the study sample confirmed the health and low-risk status of the population studied. In addition, the fetuses had low morbidity and adequate growth and development at 2 years of age. In total, 3016 and 2359 individual volumes were available for transcerebellar-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 modeling transcerebellar diameter; we then estimated gestational-age-specific 3rd , 50th and 97th smoothed centiles. Goodness-of-fit analysis comparing empirical centiles with 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% CIs between the sexes for each development score. No differences in Sylvian fissure maturation between the right and left hemispheres were observed. We present, 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. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Highlights
The fetal central nervous system undergoes extraordinary transformation throughout pregnancy
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
We present international standards for fetal cerebellar growth and Sylvian fissure (SF) maturation based on data from a large, longitudinal sample, obtained under rigorously controlled conditions, from well nourished women living in environments with minimal constraints on fetal growth, across five geographically diverse urban areas worldwide
Summary
The fetal central nervous system undergoes extraordinary transformation throughout pregnancy. The cerebellum, which is associated later in life with sensorimotor, cognitive and affective regulation[1,3], can be identified during fetal life by ultrasonography as early as 12 weeks’ gestation[4]. Ultrasonography is used to evaluate the anatomical integrity of the fetal cerebellum and linear growth of the transcerebellar diameter (TCD)[1,3,5]. Measuring the TCD enables estimation of gestational age in cases of uncertain dates in the third trimester[6,7], and may be more suitable when there are fetal growth disturbances, because cerebellar growth is less affected by placental insufficiency due to the ‘brain-sparing’ phenomenon[6,8]. A leading marker of these processes, which follow a predictable timetable[9,11,12], is the development (operculization) of the Sylvian fissure (SF) on the lateral convexities of the cerebral hemispheres
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