Early indicators for adverse development of cardiovascular, renal and metabolic function in children born with low birth weight

Abstract: Prematurity affects more than 10% of infants worldwide and is the main reason for neonatal mortality. Improvements in neonatal care have led to higher survival rates into adulthood. Adverse events during organogenesis and development, intra-or extrauterine, can increase the risk for chronic disease later in life. Developmental origins of health and disease is the epidemiologic research field linking early life events to related clinical phenotypes. In this thesis, we present 4 studies designed to follow up consequences of prematurity or low birth weight at term compared to term controls with normal birth weight in two different cohorts. The first cohort of children, studied at a mean age of 9.7 and again at 12.6 years (studies I-III), were born either very preterm (<32 weeks gestational age) or at term but small for gestational age. We studied kidney volume and function, the autonomous nervous system using heart rate variability and identified markers for insulin resistance. The second cohort of children, studied at a mean age of 7.7 years (study IV), were born extremely preterm (<28 weeks gestational age). We measured kidney volume and function and divided the group into those who developed and those who did not developed nephrocalcinosis during the neonatal period. We also studied blood pressure at the time of their visit, including 24-h ambulatory blood pressure measurements. Kidney volume or function was not significantly different between the three groups in study I. In study IV we found that children born extremely premature had smaller kidneys then children born at term, in particular the right sided kidney volume was significantly smaller compared to controls. Preterm born girls had smaller kidneys than full-term born girls (controls) but preterm born boys were not different to controls. Among preterm born children without nephrocalcinosis girls, had smaller kidney volumes than boys. Kidney function was normal and not affected by kidney volume. Paper II showed signs for insulin resistance in very preterm born children and children born small for gestational age. Preterm born children presented signs for hepatic insulin resistance while small for gestational age born children had a decreased peripheral insulin sensitivity. Both, very preterm and full-term small for gestational age born children had a generalized depression of heart rate variability compared to controls indicating an impaired function of the autonomous nervous system (study III). Office blood pressure as well as 24-hour ambulatory blood pressure were in the normal range for children born very or extremely preterm as well as for children born small for gestational age at term. Circadian blood pressure regulation was adversely affected in 50% of children born extremely preterm illustrated by the absence of normal day-to-night dipping in 24-hour ambulatory blood pressure measurements (study IV). In conclusion, children born preterm or full-term but small for gestational age showed several morphological or functional changes at early school age. The detected changes are indicating a possible development towards impaired kidney function, hypertension and the metabolic syndrome.