Prenatal Origins of Obesity: Evidence and Opportunities for Prevention
Emily Oken, MD, MPH
Harvard Medical School and Harvard Pilgrim Health Care Institute, USA
The obesity epidemic has spared no segment of the population, even infants and young children.1 In 2007-08, almost 10% of U.S. infants and toddlers were overweight.2 Recently, researchers have looked to events that occur in very early life, even before birth, to understand the causes of childhood obesity and identify factors that may be targeted for prevention.3 In this section, we outline parameters for normal growth in infancy, review prenatal factors that have been found to be associated with later obesity, and identify areas for intervention.
During well-child visits, pediatric clinicians use growth charts to document serial measures of weight and length, and screen for abnormalities in weight status.4 In the U.S., among children over the age of two, obesity is defined as a body mass index (BMI, weight in kg divided by height in m)2 above the 95th percentile for age and sex, compared with a reference population – typically the Centers for Disease Control and Prevention (CDC) 2000 growth charts.5 Overweight is a BMI between the 85th and 94th percentile.
In infants below 24 months, excess weight has traditionally been defined using weight for length percentiles compared with the CDC reference data. In the past few years, however, evidence is emerging that the World Health Organization (WHO) 2006 Growth Standard might be a better reference for healthy growth in infancy.6 WHO included only term infants who were breast-fed for at least 12 months, followed them longitudinally, and excluded data for children with excess adiposity and growth failure. Using the WHO Growth Standard fewer children are diagnosed with poor weight gain, and more with excess adiposity, than when using the CDC Growth Reference.7,8 Recent recommendations suggest the use of the WHO standard for infants below 24 months, with a BMI above the 97th percentile indicating excess adiposity.9 Since BMI reflects both lean and fat mass, however, BMI screening may result in misdiagnosis of individuals with higher or lower lean body mass than expected.
In addition to an infant’s weight at any given time, a rapid weight gain trajectory predicts later health outcomes including risk for high blood pressure and asthma.10,11 In a study of 44,622 children aged 1 month to 10 years with 122,214 length/height and weight measurements, Taveras et al. found that upward crossing of ≥ 2 major weight-for-length percentiles (i.e., the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentile lines on the growth chart) in the first 6 months of life was not only common but was also associated with the highest risk of obesity 5 and 10 years later.12
Obesity in infancy predicts obesity and related cardio-metabolic risk in later life. Also serious morbidity may occur even within childhood, including asthma, orthopedic problems, psychosocial adversity, high hospital admission rates, and increasingly, type 2 diabetes.13-18 Fat cell number, a major determinant of fat mass in adulthood, appears to be set in the first years of life.19 The fattest babies are not necessarily the biggest – babies born small for gestational age have reduced lean body mass, but are relatively fatter compared with appropriate-for-gestational age babies both at birth and in later life.20 Since the combination of low weight at birth and rapid postnatal weight gain is the strongest predictor of later disease risk, it is especially important avoid ‘fattening up’ these small babies.21
Numerous animal experiments dating back decades show that perturbations before birth can have lifelong effects on health.22,23 Whereas early studies focused on under-nutrition in early life as a risk factor for cardiovascular disease risk, more recently research has focused on over-nutrition and excess adiposity. In humans, accumulating research demonstrates that maternal prenatal obesity, excess weight gain during pregnancy, gestational diabetes, and smoking during pregnancy predict later obesity and its adverse sequelae.24-31
Key Research Questions
Current research into the developmental origins of obesity clusters around the following questions: 1) What factors in early life predict later obesity risk, and how much influence do these early life factors have compared risk factors that occur later on? 2) What are the pathways and mechanisms by which early life exposures influence later health? 3) How can we intervene in these early life exposures to prevent or ameliorate risks for obesity and its adverse health effects?
Recent Research Results
Obese mothers tend to have obese children.32-34 Initially these associations were mostly studied as evidence for a genetic underpinning of obesity risk.35 More recently, numerous investigators have found evidence that the obese intrauterine environment itself programs body weight.36 Similarly, a number of epidemiologic studies have found that higher maternal gestational weight gain is associated with higher child weight in childhood and adolescence, and consequent risk for obesity and elevated blood pressure.27,37-40 Infants born to mothers with diabetes during pregnancy are heavier at birth, but then grow slower after birth and are often no larger during the preschool years. However, even in early life they are likely to have more body fat,41 and beginning in mid-childhood these children are heavier than their peers who were not born to mothers with diabetes during pregnancy.24 Finally, although infants born to mothers who smoked during pregnancy are small at birth, they grow faster and have a higher risk for obesity in childhood and adulthood.28
The question remains whether these intrauterine experiences actually program long-term weight regulation and disease risk, or whether they are solely markers for other, shared causes of both maternal weight and child weight. Shared genes and extra-uterine environment certainly account for some of the similarity in maternal and offspring weight.42,43 For example, parents and children tend to have similar diet quality and physical activity habits.44 Also, mothers who smoke, are obese, had gestational diabetes, or gained excessive weight during pregnancy are less likely to breastfeed, which itself predicts later overweight.45-48
However, associations of these prenatal factors with child weight persist even after statistical adjustment for factors such as socioeconomic status, infant feeding, and child diet and physical activity.37 Furthermore, studies that compare siblings with discordant prenatal exposures but presumably otherwise similar genetic and extra-uterine experiences, provide additional evidence that the prenatal is a critical period for obesity risk.49-51 Also, these human findings are supported by abundant evidence from animal studies among rodents, sheep and primates.52-54
An optimal approach to understanding the role of intrauterine exposures for later health would be to conduct a well-powered randomized clinical trial, in which women are randomized to usual care or to an effective weight change intervention before and/or during pregnancy, and follow children longitudinally. No previous randomized trials have been performed of an intervention delivered before pregnancy. Trials to improve diet or other behaviours during pregnancy have generally included small numbers of women, and few have followed infants after delivery.55 To date, the limited data available suggest that studied interventions have not been successful in reducing rates of large for gestational age births.56 Ongoing studies with larger sample sizes are expected to provide additional information in the coming years.
Childhood overweight is common and an important predictor of later health. Numerous observational studies among humans and abundant experimental data from animals suggest that experiences before birth including intrauterine exposure to maternal smoking, obesity, excess gestational weight gain or diabetes can “program” trajectories of adiposity and metabolic health throughout life. Clear guidelines exist for each of these factors, including recommendations for optimal maternal BMI before pregnancy, gestational weight gain guidelines, advice against smoking during pregnancy, and recommendations for universal gestational diabetes screening.57,58 What is less clear, however, is how to help women achieve these optimal behaviours.
Implications for Parents, Service Providers, and Policy Makers
All young women should be encouraged to maintain a healthy weight and abstain from smoking prior to pregnancy. During pregnancy, provider advice is an important predictor of healthful behaviours and of weight gain concordant with guidelines. Women should be counseled regarding the implications of their own weight and health status for their child’s health.
Pediatricians should identify and document prenatal and familial factors that are likely to increase a child’s obesity risk, including parental obesity and maternal smoking, excess gestational weight gain and gestational diabetes. All infants and children should be routinely screened for overweight and for rapid weight gain using standard measurement techniques and the appropriate growth charts. The postpartum period is an opportunity to promote healthful behaviors that may not only improve the mother’s long-term health and provide a role model for the infant’s future behaviours, but also may optimize the mother’s health entering subsequent pregnancies.
- Kim J, Peterson KE, Scanlon KS, et al. Trends in Overweight from 1980 through 2001 among Preschool-Aged Children Enrolled in a Health Maintenance Organization[ast]. Obesity. 2006;14(7):1107-1112.
- Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM. Prevalence of high body mass index in US children and adolescents, 2007-2008. JAMA. Jan 20 2010;303(3):242-249.
- Oken E, Gillman MW. Fetal origins of obesity. Obes Res. Apr 2003;11(4):496-506.
- Story M, Holt K, Sofka D, eds. Bright futures in practice (Nutrition). 2nd ed. Arlington, VA: National Center for Education in Maternal and Child Health; 2002.
- Centers for Disease Control and Prevention, National Center for Health Statistics. CDC Growth Charts: United States. 2000.
- World Health Organization. WHO child growth standards: length/height-for-age, weight-for-age, weight-for-height and body mass index-for-age: Methods and development. Geneva, Switzerland: World Health Organization; 2006.
- Maalouf-Manasseh Z, Metallinos-Katsaras E, Dewey KG. Obesity in preschool children is more prevalent and identified at a younger age when WHO growth charts are used compared with CDC charts. J Nutr. Jun 2011;141(6):1154-1158.
- Parsons HG, George MA, Innis SM. Growth assessment in clinical practice: whose growth curve? Curr Gastroenterol Rep. Jun 2011;13(3):286-292.
- Grummer-Strawn LM, Reinold C, Krebs NF. Use of World Health Organization and CDC growth charts for children aged 0-59 months in the United States. MMWR Recomm Rep. Sep 10 2010;59(RR-9):1-15.
- Taveras EM, Camargo CA, Jr., Rifas-Shiman SL, et al. Association of birth weight with asthma-related outcomes at age 2 years. Pediatr Pulmonol. Jul 2006;41(7):643-648.
- Belfort MB, Rifas-Shiman SL, Rich-Edwards J, Kleinman KP, Gillman MW. Size at birth, infant growth, and blood pressure at three years of age. J Pediatr. Dec 2007;151(6):670-674.
- Taveras EM, Rifas-Shiman SL, Sherry B, et al. Crossing growth percentiles in infancy and risk of obesity in childhood. Arch Pediatr Adolesc Med. Nov 2011;165(11):993-998.
- Charney E, Goodman HC, McBride M, Lyon B, Pratt R. Childhood antecedents of adult obesity. Do chubby infants become obese adults? N Engl J Med. Jul 1 1976;295(1):6-9.
- Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, Looker HC. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med. Feb 11 2010;362(6):485-493.
- Biro FM, Wien M. Childhood obesity and adult morbidities. Am J Clin Nutr. May 2010;91(5):1499S-1505S.
- Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med. Mar 14 2002;346(11):802-810.
- Noal RB, Menezes AM, Macedo SE, Dumith SC. Childhood body mass index and risk of asthma in adolescence: a systematic review. Obes Rev. Feb 2011;12(2):93-104.
- Shibli R, Rubin L, Akons H, Shaoul R. Morbidity of overweight (>or=85th percentile) in the first 2 years of life. Pediatrics. Aug 2008;122(2):267-272.
- Spalding KL, Arner E, Westermark PO, et al. Dynamics of fat cell turnover in humans. Nature. Jun 5 2008;453(7196):783-787.
- Hediger ML, Overpeck MD, Kuczmarski RJ, McGlynn A, Maurer KR, Davis WW. Muscularity and fatness of infants and young children born small- or large-for-gestational-age. Pediatrics. 1998;102(5):E60.
- Barker D. Mothers, babies, and health in later life. Second ed. Edinburgh: Harcourt Brace and Company; 1998.
- McCance RA, Widdowson EM. The determinants of growth and form. Proc R Soc Lond. 1974;185:1-17.
- Plagemann A, Heidrich I, Gotz F, Rohde W, Dorner G. Obesity and enhanced diabetes and cardiovascular risk in adult rats due to early postnatal overfeeding. Exp Clin Endocrinol. 1992;99(3):154-158.
- Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. Mar 2003;111(3):e221-226.
- Moore TR. Fetal exposure to gestational diabetes contributes to subsequent adult metabolic syndrome. Am J Obstet Gynecol. Jun 2010;202(6):643-649.
- Oken E, Huh SY, Taveras EM, Rich-Edwards JW, Gillman MW. Associations of maternal prenatal smoking with child adiposity and blood pressure. Obes Res. Nov 2005;13(11):2021-2028.
- Oken E, Kleinman KP, Belfort MB, Hammitt JK, Gillman MW. Associations of gestational weight gain with short- and longer-term maternal and child health outcomes. Am J Epidemiol. Jul 15 2009;170(2):173-180.
- Oken E, Levitan EB, Gillman MW. Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis. Int J Obes (Lond). Feb 2008;32(2):201-210.
- Oken E, Rifas-Shiman SL, Field AE, Frazier AL, Gillman MW. Maternal gestational weight gain and offspring weight in adolescence. Obstet Gynecol. Nov 2008;112(5):999-1006.
- Taveras EM, Rifas-Shiman SL, Oken E, Gunderson EP, Gillman MW. Short Sleep Duration in Infancy and Risk of Childhood Overweight. Arch Pediatr Adolesc Med. 2008;162(4):305-311.
- Taveras EM, Sandora TJ, Shih MC, Ross-Degnan D, Goldmann DA, Gillman MW. The association of television and video viewing with fast food intake by preschool-age children. Obesity (Silver Spring). Nov 2006;14(11):2034-2041.
- Guillaume M, Lapidus L, Beckers F, Lambert A, Bjorntorp P. Familial trends of obesity through three generations. Int J Obes Relat Metab Disord. 1995;19 Suppl 3:S5-9.
- Lake JK, Power C, Cole TJ. Child to adult body mass index in the 1958 British birth cohort: associations with parental obesity. Arch Dis Child. Nov 1997;77(5):376-381.
- Fisch RO, Bilek MK, Ulstrom R. Obesity and leanness at birth and their relationship to body habitus in later childhood. Pediatrics. 1975;56(4):521-528.
- Stunkard AJ, Sorensen TI, Hanis C, et al. An adoption study of human obesity. N Engl J Med. Jan 23 1986;314(4):193-198.
- Oken E. Maternal and child obesity: the causal link. Obstet Gynecol Clin North Am. Jun 2009;36(2):361-377, ix-x.
- Oken E, Taveras EM, Kleinman KP, Rich-Edwards JW, Gillman MW. Gestational weight gain and child adiposity at age 3 years. Am J Obstet Gynecol. Apr 2007;196(4):322 e321-328.
- Wrotniak BH, Shults J, Butts S, Stettler N. Gestational weight gain and risk of overweight in the offspring at age 7 y in a multicenter, multiethnic cohort study. Am J Clin Nutr. Jun 2008;87(6):1818-1824.
- Oken E, Rifas-Shiman SL, Field AE, Frazier AL, Gillman MW. Maternal gestational weight gain and offspring weight in adolescence. Obstet Gynecol. Nov 2008;112(5):999-1006.
- Seidman DS. Excessive maternal weight gain during pregnancy and being overweight at 17 years of age [abstract]. Pediatr Res. 1996;39:112A.
- Wright CS, Rifas-Shiman SL, Rich-Edwards JW, Taveras EM, Gillman MW, Oken E. Intrauterine exposure to gestational diabetes, child adiposity, and blood pressure. Am J Hypertens. Feb 2009;22(2):215-220.
- Rankinen T, Zuberi A, Chagnon YC, et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring). Apr 2006;14(4):529-644.
- Nelson MC, Gordon-Larsen P, North KE, Adair LS. Body mass index gain, fast food, and physical activity: effects of shared environments over time. Obesity (Silver Spring). Apr 2006;14(4):701-709.
- Oliveria SA, Ellison RC, Moore LL, Gillman MW, Garrahie EJ, Singer MR. Parent-child relationships in nutrient intake: the Framingham Children's Study. Am J Clin Nutr. Sep 1992;56(3):593-598.
- Gunderson EP. Breastfeeding after gestational diabetes pregnancy: subsequent obesity and type 2 diabetes in women and their offspring. Diabetes Care. Jul 2007;30 Suppl 2:S161-168.
- Li R, Jewell S, Grummer-Strawn L. Maternal obesity and breast-feeding practices. Am J Clin Nutr. Apr 2003;77(4):931-936.
- Hilson JA, Rasmussen KM, Kjolhede CL. Excessive weight gain during pregnancy is associated with earlier termination of breast-feeding among White women. J Nutr. Jan 2006;136(1):140-146.
- Hilson JA, Rasmussen KM, Kjolhede CL. High pre-pregnant body mass index is associated with poor lactation outcomes among white, rural women independent of psychosocial and demographic correlates. J Hum Lact. Feb 2004;20(1):18-29.
- Dabelea D, Hanson RL, Lindsay RS, et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. Dec 2000;49(12):2208-2211.
- Ludwig DS, Currie J. The association between pregnancy weight gain and birthweight: a within-family comparison. Lancet. Sep 18 2010;376(9745):984-990.
- Smith J, Cianflone K, Biron S, et al. Effects of maternal surgical weight loss in mothers on intergenerational transmission of obesity. J Clin Endocrinol Metab. Nov 2009;94(11):4275-4283.
- Howie GJ, Sloboda DM, Kamal T, Vickers MH. Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol. Feb 15 2009;587(Pt 4):905-915.
- Wu Q, Suzuki M. Parental obesity and overweight affect the body-fat accumulation in the offspring: the possible effect of a high-fat diet through epigenetic inheritance. Obes Rev. May 2006;7(2):201-208.
- Robinson S, Marriott L, Poole J, et al. Dietary patterns in infancy: the importance of maternal and family influences on feeding practice. Br J Nutr. Nov 2007;98(5):1029-1037.
- Oken E, Gillman MW. Intervention strategies to improve outcome in obese pregnancy I: Focus on Gestational Weight gain. In: Gillman MW, Poston L, eds. Maternal Obesity. Cambridge, UK: Cambridge University Press; 2012.
- Dodd JM, Grivell RM, Crowther CA, Robinson JS. Antenatal interventions for overweight or obese pregnant women: a systematic review of randomised trials. Bjog. Oct 2010;117(11):1316-1326.
- Institute of Medicine and National Research Council of the National Academies. Weight Gain During Pregnancy: Reexamining the Guidelines. Washington, DC: National Academies Press; 2009.
- American Diabetes Association. Standards of medical care in diabetes--2011. Diabetes Care. Jan 2011;34 Suppl 1:S11-61.
How to cite this article:
Oken E. Prenatal Origins of Obesity: Evidence and Opportunities for Prevention. In: Tremblay RE, Boivin M, Peters RDeV, eds. Fisher JO, topic ed. Encyclopedia on Early Childhood Development [online]. http://www.child-encyclopedia.com/child-obesity/according-experts/prenatal-origins-obesity-evidence-and-opportunities-prevention. Published April 2012. Accessed September 26, 2018.