Fetal Growth versus Birthweight: The Role of Placenta versus Other Determinants Marie Cecilie Paasche Roland 1 *, Camilla M. Friis 1 , Nanna Voldner 1 , Kristin Godang 2 , Jens Bollerslev 2,3 , Guttorm Haugen 1,3 , Tore Henriksen 1,3 1 Department of Obstetrics, Oslo University Hospital, Oslo, Norway, 2 Department of Specialized Endocrinology, Oslo University Hospital, Oslo, Norway, 3 University of Oslo, Oslo, Norway Abstract Introduction: Birthweight is used as an indicator of intrauterine growth, and determinants of birthweight are widely studied. Less is known about determinants of deviating patterns of growth in utero. We aimed to study the effects of maternal characteristics on both birthweight and fetal growth in third trimester and introduce placental weight as a possible determinant of both birthweight and fetal growth in third trimester. Methods: The STORK study is a prospective cohort study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (age, parity, body mass index (BMI), gestational weight gain and fasting plasma glucose) of birthweight and fetal growth estimated by biometric ultrasound measures were explored by linear regression models. Two models were fitted, one with only maternal characteristics and one which included placental weight. Results: Placental weight was a significant determinant of birthweight. Parity, BMI, weight gain and fasting glucose remained significant when adjusted for placental weight. Introducing placental weight as a covariate reduced the effect estimate of the other variables in the model by 62% for BMI, 40% for weight gain, 33% for glucose and 22% for parity. Determinants of fetal growth were parity, BMI and weight gain, but not fasting glucose. Placental weight was significant as an independent variable. Parity, BMI and weight gain remained significant when adjusted for placental weight. Introducing placental weight reduced the effect of BMI on fetal growth by 23%, weight gain by 14% and parity by 17%. Conclusion: In conclusion, we find that placental weight is an important determinant of both birthweight and fetal growth. Our findings indicate that placental weight markedly modifies the effect of maternal determinants of both birthweight and fetal growth. The differential effect of third trimester glucose on birthweight and growth parameters illustrates that birthweight and fetal growth are not identical entities. Citation: Roland MCP, Friis CM, Voldner N, Godang K, Bollerslev J, et al. (2012) Fetal Growth versus Birthweight: The Role of Placenta versus Other Determinants. PLoS ONE 7(6): e39324. doi:10.1371/journal.pone.0039324 Editor: Nick Harvey, University of Southampton, United Kingdom Received January 29, 2012; Accepted May 19, 2012; Published June 18, 2012 Copyright: ß 2012 Roland et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This project has been financially supported by: University of Oslo; Thematic research: Perinatal nutrition. Oslo University Hospital, Department of Obstetrics. The Norwegian Health Association. The Norwegian Extrafoundation for Health and Rehabilitation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: mcpaasche@hotmail.com Introduction Birthweight is associated with long term effects on health and disease in adult life. Low birthweight is a well established risk factor for adverse long term health, particularly cardiovascular disease and metabolic syndrome [1]. Numerous studies have identified determinants of abnormal birthweight, particularly low birthweight, but also more recently of high birthweight [2–4]. Birthweight is used as an indicator of intrauterine growth. The actual pattern of growth in utero can, however, only be estimated by serial ultrasound measurements during pregnancy. Far less is known about determinants of deviating patterns of growth in utero than that of abnormal birthweights. Fetal growth is a result of multiple factors including genetic potential for growth, maternal nutrition, maternal metabolism, endocrine factors and placental perfusion and function [5]. In addition, the ability of the fetus to respond to nutrients and other growth regulatory factors may play a role. The Hyperglycaemia and Adverse Pregnancy Outcomes study (HAPO) has established maternal blood glucose and body mass index (BMI) as independent determinants of large for gestational age (LGA) newborns and excessive body fat at birth [6,7]. It is implicative in these findings that maternal plasma glucose and other not specified biological factors associated with maternal BMI affect fetal growth and neonatal body composition. The biological mechanisms underlying the effect of glucose on fetal growth are best explained by the Pedersen hypothesis [8]. Pedersen postulated that maternal hyperglycemia was transferred to the fetus, which, in turn, produced and released large amounts of insulin, with fetal hyperinsulinemia as a result. However, the independent effect of BMI is not well explained by any hypotheses that consistently fit observations to the extent that the Pedersen hypothesis does. PLoS ONE | www.plosone.org 1 June 2012 | Volume 7 | Issue 6 | e39324