Lower hypothalamus subunit volumes link with long-term growth failure after preterm birth: a longitudinal case-control study

Background Preterm birth is associated with an increased risk for impaired growth. While it is known that in prematurity several somatic to environmental factors such as endocrine factors or nutrition modulate short- and long-term growth failure, the contribution of potentially impaired growth control in the brain remains elusive. We hypothesized that the structure of hypothalamic nuclei involved in growth control is altered after preterm birth, with these alterations being associated with aberrant weight development into adulthood. Methods We assessed 101 very preterm (i.e., <32 weeks of gestational age) and/or very low birth weight (i.e., <1500g; VP/VLBW) and 110 full-term born (FT) adults of the population-based Bavarian Longitudinal Study with T1-weighted MRI, deep learning-based hypothalamus subunit segmentation, and multiple body weight assessments from birth into adulthood. Results Volumes of the whole hypothalamus and hypothalamus subunits relevant for growth control were reduced in VP/VLBW adults and associated with birth variables (i.e., gestational age and intensity of neonatal treatment), body weight (i.e., weight at birth and adulthood), and growth trajectories (i.e., trajectory slopes and trajectories of those small for gestational age and with long-term catch-up growth). Concerning VP/VLBW weight trajectories, relatively larger hypothalamic volumes comparable to those of FT adults, especially in subunits including the lateral hypothalamus, were associated with favorable long-term growth trajectories. Conclusions Results: demonstrate lower volumes of growth control-related hypothalamus sub-units after preterm birth that link with long-term growth failure. Data suggest postnatal development of growth-related hypothalamic nuclei in VP/VLBW individuals that corresponds with distinct body growth trajectories into adulthood. Funding This study was supported by the Deutsche Forschungsgemeinschaft (BA 6370/2-1 to C.S.), the German Federal Ministry of Education and Science (BMBF 01ER0801 to P.B. and D.W., BMBF 01ER0803 to C.S.) and the Kommission für Klinische Forschung, Technische Universität München (KKF 8700000474 to D.M.H.).