About 3% of human fetuses are born small for gestational age (SGA). More than 90% of those SGA infants catch-up growth and normalise their body size by the age of 2 yr.
Longitudinal studies have disclosed that SGA-catch-up children tend to become hyperinsulinemic, viscerally adipose and to show an abnormal adipokine profile by 4–6 years of age, even if not obese. Between 6 and 8 years, their circulating levels of sex hormone binding globulin (SHBG) start to be low, and those of dehydroepiandrosterone-sulphate (DHEAS) start to be high; in girls, precocious pubarche (pubic hair < 8 yr) may emerge as clinical marker. A mismatch between early adipogenesis and later lipogenesis, accounting for lipotoxicity, dys-adipokinemia and insulin resistance, seems to encompass this sequence; postnatal overweight amplify these risks. Beyond the age of 8 years, such SGA children tend to experience an early onset of puberty with rapid progression, that may lead to a lower adult stature; low birthweight girls with precocious pubarche are also at increased risk for developing hyperinsulinemic androgen excess in adolescence. In these girls, insulin sensitisation with metformin started in prepuberty and maintained throughout puberty appears to decrease visceral and hepatic adiposity, and to have normalising effects on serum insulin, lipids, leptin and adipokines, on the tempo of puberty, on final stature, and on the prevalence of androgen excess in adolescence.