CLINICAL STUDY Impact of fetal growth restriction on body composition and hormonal status at birth in infants of small and appropriate weight for gestational age R Verkauskiene, J Beltrand, O Claris 1 , D Chevenne 2 , S Deghmoun, S Dorgeret 3 , M Alison 3 , P Gaucherand 4 , O Sibony 5 and C Le ´vy-Marchal INSERM, Unite ´ de recherche U690, Ho ˆpital Robert Debre ´, 48, bd Serurier, 75019 Paris, France, 1 Service de Ne ´onatologie, Ho ˆpital Edouard Herriot, Lyon, France, 2 Service de biochimie et d’hormonologie, 3 Service d’Imagerie Me ´dicale, Ho ˆpital Robert Debre ´, Paris, France, 4 Service de Chirurgie Gynecologie- Obstetrique, Ho ˆpital Eduard Herriot, Lyon, France and 5 Service de Chirurgie Gynecologie-Obstetrique, Ho ˆpital Robert Debre ´, Paris, France (Correspondence should be addressed to RVerkauskiene; Email: rasa.verkauskiene@yahoo.com) Abstract Background: Fetal growth restriction (FGR) has been related to several health risks, which have been generally identified in small-for-gestational age (SGA) individuals. Objective: To evaluate the impact of FGR on body composition and hormonal status in infants born either small- or appropriate-for-gestational age (AGA). Methods: Fetal growth was assessed by ultrasound every 4 weeks from mid-gestation to birth in 248 high-risk pregnancies for SGA. Fetal growth velocity was calculated as change in the estimated fetal weight percentiles and FGR defined as its reduction by more than 20 percentiles from 22 gestational weeks to birth. Impact of FGR on body composition, cord insulin, IGF-I, IGF binding protein-3 (IGFBP-3), and cortisol concentrations was assessed in SGA and AGA newborns. Results: Growth-retarded AGA infants showed significantly reduced birth weight, ponderal index, percentage of fat mass, and bone mineral density when compared with AGA newborns with stable intrauterine growth. Cord IGF-I and IGFBP-3 concentrations were significantly decreased in growth- retarded infants in both SGA and AGA groups. Cord insulin concentration was significantly lower and cord cortisol significantly higher in AGA infants with FGR versus AGA newborns with stable intrauterine growth.After adjustment for gestational ageand gender, birth weight was directly related to fetal growth velocity and cord IGF-I concentration. The variation in infant’s adiposity was best explained by fetal growth velocity and cord insulin concentration. Conclusions: FGR affects body composition and hormonal parameters in newborns with birth weight within the normal range, suggesting these individuals could be at similar metabolic risks as SGA. European Journal of Endocrinology 157 605–612 Introduction A number of short- and long-term health risks for subjects born small-for-gestational age (SGA) have been identified. It is well recognized that fetuses at the extremes of normal birth weight range are at an increased risk of perinatal morbidity, mortality, and adverse developmental outcomes (1, 2). The long-term consequences of small size at birth have also been reported by numerous studies, including hypertension (3), increased cardiovascular mortality (4), insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus (5, 6). Recent research has suggested that programming of the endocrine axis and the cardiovascular system occurs during fetal development and may be affected by intrauterine growth retardation (IUGR) (7). A vast majority of these studies referred to individuals born SGA, a term that refers to size at birth but not to intrauterine growth pattern. However, not all SGA babies will suffer from IUGR and not all growth- retarded fetuses will be born SGA (8). Birth weight is a final result of fetal growth in utero, and IUGR or fetal growth restriction (FGR) are terms that indicate fetal growth pattern with reduced fetal growth velocity, presuming that at least two assessments of fetal size at different time points are available. Separating small babies, who are small simply as a result of adaptation to maternal size, from those who have suffered FGR presents a diagnostic challenge, because it is the FGR group which is at an increased perinatal risk and needs to be identified clinically (2). In addition to gestational age and gender, other pregnancy characteristics, such as maternal height and weight before pregnancy, parity, and ethnicity, account for a considerable part of the variation in fetal growth velocity and weight at birth (9). A computer European Journal of Endocrinology (2007) 157 605–612 ISSN 0804-4643 q 2007 Society of the European Journal of Endocrinology DOI: 10.1530/EJE-07-0286 Online version via www.eje-online.org