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Prenatal and Early Life Influences

Understanding Obesity’s Developmental Origins

Obesity, once thought to be little more than an unfortunate failure of will and self-restraint, has much deeper and more complex roots. Genes clearly play a role in driving an individual’s propensity to gain excess weight, as does the environment and gene–environment interactions. Early-life influences, beginning with the intrauterine environment and continuing through the first few years of life, also shape the trajectory of weight gain and body fatness throughout the life course.

 

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If a mother smokes during pregnancy or gains too much weight, there’s a greater chance that her child will be obese. Lack of sleep or too-rapid weight gain during infancy may also increase obesity risk. Learn more about prenatal and early life factors that affect weight.

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In the 1980s, intriguing research from British epidemiologist David Barker and colleagues sparked a flutter of research into what was then called the “fetal origins hypothesis” of chronic disease. (1) They proposed that coronary heart disease, type 2 diabetes, stroke, hypertension, and other chronic diseases develop in part due to undernutrition during fetal life and infancy. (2)

Later data showing that higher birth weight is also associated with obesity, diabetes, and other adult diseases has helped extend this concept into the “developmental origins hypothesis,” which encompasses the preconception period as well as many critical periods of fetal and infant development. During each of these periods, several factors appear to have a substantial impact on obesity in childhood and adulthood. This article briefly outlines some of the key prenatal and early life influences on the development of adult weight and obesity.

Prenatal Influences on Obesity

The warm, nutrient- and hormone-rich environment of the uterus has a profound effect on fetal development. Brief or fluctuating changes in the intrauterine environment at critical or sensitive periods of the developmental process, as well as longer term alterations, could have irreversible, lifelong consequences. Three modifiable prenatal factors that appear to shape fetal nutrition and health in later life are

  • the mother’s smoking habits during pregnancy;
  • the mother’s weight gain during pregnancy; and
  • the mother’s blood sugar levels during pregnancy, specifically, whether she develops pregnancy-related (gestational) diabetes.

It makes intuitive sense that the mother’s diet during pregnancy should also affect fetal development and birth weight, but evidence for this is inconsistent.

Maternal Smoking During Pregnancy and Child Obesity Risk

Although smoking during pregnancy tends to slow the rate of fetal growth, children of women who smoke during pregnancy are more likely to be obese than the children of women who don’t. In a meta-analysis of 14 studies, maternal smoking during pregnancy was associated with a 50 percent higher risk of childhood obesity. Most of the studies looked at children’s obesity status at ages 3 to 7; one study assessed obesity at age 14, and another tracked the children all the way to young adulthood. (3)

Gestational Weight Gain and Childhood Obesity Risk

Excessive weight gain during pregnancy is more common now than it was in 1990 when the Institute of Medicine (IOM) first offered recommendations for pregnancy-related weight gain. (4) In addition, more women are beginning pregnancy overweight or obese. These worrisome changes prompted the IOM to reevaluate what constitutes healthy weight gain during pregnancy, with new evidence suggesting that weight gain scale (scale.jpg)once considered normal by the IOM actually increases the risk of childhood obesity.

Project Viva, for example, is a Boston-area study that began following more than 2,000 pregnant women and their offspring from soon after the women discovered they were pregnant, and it will continue following the women and children at least through early adolescence. Using data from this cohort, investigators looked at the relationship between a mother’s weight gain during pregnancy, defined by the 1990 IOM guidelines, and her child’s risk of obesity at age 3.

Children of women who gained an “excessive” amount of weight had more than four times the risk of being overweight at age 3, compared with children of women who gained an “inadequate” amount of weight. Even women who gained what was considered at the time to be an “adequate” amount of weight bore children who were nearly four times more likely to be overweight at age 3 than children of women who gained an “inadequate” amount of weight. (5)

More recently, a population-based cohort study of sibling births in Michigan and New Jersey between 1989 and 2003 noted a consistent association between pregnancy weight gain and birth weight among 513,501 women and their 1,164,750 offspring. (6) Compared with infants of women who gained 18–22 pounds during pregnancy, infants of women who gained more than 53 pounds during pregnancy were about 5 ounces heavier at birth and were twice as likely to weigh more than 8.8 pounds at birth.

Based on these studies and other evidence, new guidelines from the IOM steer clinicians and women to more moderate weight gain goals during pregnancy for women who are obese. Women with a pre-pregnancy BMI in the normal range (18.5 to 24.9) should gain 25–35 pounds, for example, whereas women with a BMI between 25.0 and 29.9 should gain only 15–25 pounds; women with a BMI of 30 or higher should gain only 11–20 pounds. (7)

Gestational Diabetes and Child Obesity Risk

Weight gained during pregnancy is primarily adipose (fat) tissue. Proliferation of adipose tissue is often accompanied by a state of relative insulin resistance starting in mid-pregnancy. This adaptive response allows for more efficient transfer of glucose and other fuels across the placenta, so the fetus can grow. But it may also subject the fetus to periods of high blood glucose and elevated insulin. These can lead to increased body fat, which generally manifests as larger size at birth. (7) Many studies show that birth weight is directly associated with later BMI, (8-10) so it makes sense that gestational diabetes in a mother may contribute to obesity in her child.

Starting Pregnancy at a Healthy Weight (starting-pregnancy-at-a-healthy-weight.jpg)Maternal BMI at the beginning of pregnancy is a strong risk factor for offspring obesity and other conditions. (13) Once pregnancy begins, however, it is not a modifiable factor—and no one is recommending that women try to lose weight during pregnancy. That’s why achieving a healthy BMI before pregnancy begins is one of the most important goals for preventing obesity across generations. (14)

Indeed, among 5- to 7-year old children in two American health plans, the risk of having a high weight for age was increased among those whose mothers had untreated gestational diabetes, compared with children whose mothers did not have diabetes. Among children whose mothers received treatment for gestational diabetes, the risk was lower, about equal to that of children whose mothers had less severe glucose intolerance. (11)

Although these data suggest that treatment of gestational diabetes could lower the risk of childhood obesity, a more recent study of 4- to 5-year-old children whose mothers participated in a gestational diabetes treatment trial found no difference in obesity rates between children of women who received treatment for mild gestational diabetes and children of women who did not. (12) The jury is still out on the extent to which gestational diabetes causes childhood obesity, but preventing and treating gestational diabetes benefits the baby in other ways.

Postnatal Influences on Obesity

Environmental influences don’t stop with birth. Instead, they merely shift from a small, confined space largely controlled by the mother’s genes, lifestyle, and physiology to an unbounded environment with equally influential effects. Three modifiable postnatal factors during infancy that influence weight in later life include

Infant Weight Gain and Obesity Risk

Accelerated weight gain during the first weeks or months of life is associated with higher BMI or obesity later in life. A systematic review by Baird and colleagues in 2005 looked at 10 studies of infant weight-gain patterns and later obesity risk. Seven of the 10 found that infants with more rapid early growth had a higher risk of later obesity than infants with normal growth. (15)

Breastfeeding and Obesity Risk

The initiation and duration of breastfeeding may influence obesity in later life, although this is a controversial area of research. (16) In two meta-analyses of breastfeeding versus bottle feeding, breastfeeding was associated with a 13 percent and a 22 percent reduced risk of obesity in later life. (17, 18) Duration of breastfeeding may matter: A meta-analysis of 17 studies of breastfeeding duration found that each additional month that infants were breastfed was associated with a 4 percent lower risk of obesity later in life. (16)

It is not clear that breastfeeding itself actually prevents obesity, however, as both breastfeeding and obesity may be influenced by similar socioeconomic and cultural factors. Although debate lingers over whether breastfeeding protects against childhood obesity, breastfeeding has many other proven health benefits for infants and their mothers, and it should be promoted regardless of its relationship to childhood obesity. (Read more about the health and other benefits of breastfeeding in The Surgeon General’s Call to Action to Support Breastfeeding.)

Infant Sleep Duration and Obesity Riskbassinet2 (bassinet2.jpg)

Intriguing work has revealed an association between short sleep duration and weight gain in adults. (19) A similar association may hold for infants.

In a prospective cohort study of 915 children, infants who slept fewer than 12 hours a day had double the odds of being overweight at age 3, compared with infants who slept more than 12 hours a day. (20) Factors associated with shorter infant sleep duration include maternal depression during pregnancy, early introduction of solid foods (before 4 months), and infant TV viewing. (21)

Combining Pre- and Postnatal Factors: Increased Obesity Risk

Although prenatal and postnatal determinants of obesity operate at different times in the life course, they have additive or synergistic effects and must be considered together when trying to gauge the impact of developmental influences on obesity in later life.

Using data from 1,100 mother–child pairs enrolled in Project Viva, Gillman and colleagues modeled the impact of four potentially modifiable developmental determinants of obesity—maternal smoking during pregnancy, gestational weight gain, duration of breastfeeding, and infant sleep—on child obesity at age 3. Among children with optimal levels of all four (those whose mothers did not smoke and did not gain too much weight during pregnancy, who were breastfed for at least one year, and who got at least 12 hours of sleep on an average night), the predicted probability of overweight was 6 percent. Among children who had adverse levels of all four factors, the probability of being overweight at age 3 was 29 percent. (22) Such a range suggests that targeted interventions could substantially reduce childhood obesity and its consequences later in life.

The Bottom Line: Healthy Behaviors During—and Even Before—Pregnancy Can Help Prevent Obesity

Nutrition and other lifestyle factors during several early periods in the lifecycle—just before conception, the months spent in utero, and the months after birth—can have profound effects on an individual’s weight at birth, during childhood, and on into adulthood. These are also potentially optimal times for intervention, for two reasons: Women may be more receptive to making lifestyle changes as they prepare to get pregnant and when they are pregnant to increase the likelihood of having a healthy baby. And after giving birth, many women are willing to make substantial changes to raise a healthy infant. Here are five key messages for clinicians to give to women of childbearing age that could help improve their health and the health of their children, and limit the current epidemic of obesity:

  • Strive for a healthy weight before pregnancy.
  • Don’t smoke during pregnancy.
  • Aim for a reasonable weight gain during pregnancy.
  • Breastfeed (preferably without other liquids for 4–6 months and some breastfeeding for at least 12 months).
  • Ensure infants get adequate sleep during the first few years of life.

References

1. Barker DJ. Mothers, Babies, and Health in Later Life. Edinburgh; New York: Churchill Livingstone, 1998.

2. Barker DJ. The developmental origins of adult disease. J Am Coll Nutr. 2004; 23:588S–595S.

3. Oken E, Levitan EB, Gillman MW. Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis. Int J Obes. (Lond) 2008; 32:201–10.

4. Institute of Medicine. Nutrition during pregnancy: part I: weight gain, part II: nutrient supplements. Washington, D.C.: National Academy Press, 1990.

5. 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. 2007; 196:322 e1–8.

6. Ludwig DS, Currie J. The association between pregnancy weight gain and birthweight: a within-family comparison. Lancet. 2010; 376:984–90.

7. Institute of Medicine. Weight gain during pregnancy: reexamining the guidelines. Washington, D.C.: National Academy Press, 2009.

8. Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003; 111:e221–6.

9. Parsons TJ, Power C, Logan S, Summerbell CD. Childhood predictors of adult obesity: a systematic review. Int J Obes Relat Metab Disord. 1999; 23 Suppl 8:S1–107.

10. Rogers I. The influence of birthweight and intrauterine environment on adiposity and fat distribution in later life. Int J Obes Relat Metab Disord. 2003; 27:755–77.

11. Hillier TA, Pedula KL, Schmidt MM, Mullen JA, Charles MA, Pettitt DJ. Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia. Diabetes Care. 2007; 30:2287–92.

12. Gillman MW, Oakey H, Baghurst PA, Volkmer RE, Robinson JS, Crowther CA. Effect of treatment of gestational diabetes mellitus on obesity in the next generation. Diabetes Care. 2010; 33:964–8.

13. Whitaker RC. Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics. 2004; 114:e29–36.

14. Gillman MW. Developmental origins of obesity. In: Hu FB, ed. Obesity Epidemiology. New York: Oxford University Press, 2008; 399–415.

15. Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C. Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ. 2005; 331:929.

16. Harder T, Bergmann R, Kallischnigg G, Plagemann A. Duration of breastfeeding and risk of overweight: a meta-analysis. Am J Epidemiol. 2005; 162:397–403.

17. Arenz S, Ruckerl R, Koletzko B, von Kries R. Breast-feeding and childhood obesity—a systematic review. Int J Obes Relat Metab Disord. 2004; 28:1247-56.

18. Owen CG, Martin RM, Whincup PH, Smith GD, Cook DG. Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Pediatrics. 2005; 115:1367–77.

19. Patel SR. Reduced sleep as an obesity risk factor. Obes Rev. 2009; 10 Suppl 2:61–8.

20. 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; 162:305–11.

21. Nevarez MD, Rifas-Shiman SL, Kleinman KP, Gillman MW, Taveras EM. Associations of early life risk factors with infant sleep duration. Acad Pediatr. 2010; 10:187–93.

22. Gillman MW, Rifas-Shiman SL, Kleinman K, Oken E, Rich-Edwards JW, Taveras EM. Developmental origins of childhood overweight: potential public health impact. Obesity (Silver Spring). 2008; 16:1651–6.

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