Early life risk factors in cancer: The relation of birth weight to adult obesity
Article first published online: 6 DEC 2002
Copyright © 2002 Wiley-Liss, Inc.
International Journal of Cancer
Volume 103, Issue 6, pages 789–791, 1 March 2003
How to Cite
Leong, N. M., Mignone, L. I., Newcomb, P. A., Titus-Ernstoff, L., Baron, J. A., Trentham-Dietz, A., Stampfer, M. J., Willett, W. C. and Egan, K. M. (2003), Early life risk factors in cancer: The relation of birth weight to adult obesity. Int. J. Cancer, 103: 789–791. doi: 10.1002/ijc.10886
- Issue published online: 3 JAN 2003
- Article first published online: 6 DEC 2002
- Manuscript Accepted: 10 OCT 2002
- Manuscript Revised: 7 OCT 2002
- Manuscript Received: 22 JUL 2002
- birth weight;
- body mass index;
The intrauterine environment appears to play a role in the development of adult diseases, including several prominent cancers. Our study aims to characterize the relationship between birth weight, a measure of the intrauterine environment, and adult obesity. A population-based sample of women aged 50–79, living in the states of Massachusetts, New Hampshire or Wisconsin, were randomly selected from lists of licensed drivers and Medicare beneficiaries to participate as controls in a case-control study of breast cancer. Information on birth weight, adult height and adult weight were collected through structured telephone interviews from 1992–1995. Our analysis was based on 1,850 interviews. A U-shaped relationship between birth weight and adult BMI was observed. Median adult BMI for the birth weight categories (in kilograms) <2.3, 2.3<2.5, 2.5<3.2, 3.2<3.9, 3.9<4.5 and ≥4.5 were 26.6, 24.4, 25.1, 25.5, 25.4 and 26.6 kg/m respectively. Compared to women 2.5<3.2 kg at birth, women in highest birth weight category (≥4.5 kg) had an odds ratio of 1.99 (95% CI 1.13–3.48) of being obese (≥30 kg/m2) as adults. The odds ratio for women in the <2.3 kg birth weight category was 1.67 (95% CI 1.01–2.76). These data suggest that both low and high birth weights are associated with higher adult BMI and support the hypothesis that fetal experience may influence adult obesity with potential consequences for risk of several major cancers. © 2002 Wiley-Liss, Inc.
Obesity and adult weight gain are associated with cancers at several sites including the breast,1, 2 colorectum,3, 4, 5 endometrium6, 7, 8 and prostate.9, 10 There is evidence that early life factors play a role in the development of obesity in later life. Several studies have found a positive correlation between birth weight, a measure of the intrauterine environment, and adult BMI.11 Maternal undernutrition during gestation has also been linked to adult obesity.12 A higher birth weight may increase the risk of breast cancer.13, 14 In our study, we investigated the association between birth weight and adult BMI in a large, population-based sample of women in the United States.
MATERIAL AND METHODS
The Collaborative Breast Cancer Study was a case-control study of the determinants for breast cancer conducted in the states of Massachusetts, New Hampshire and Wisconsin. We limited our present analysis to controls. The women, aged 50–79, were randomly selected from lists of licensed drivers (for ages 64 and younger) and Medicare beneficiaries (65 and older). Structured telephone interviews were conducted from 1992–1995. Women were asked how much they weighed at birth, their current weight, and their current height. Body mass index (kg/m2) was calculated for each subject (n = 1,851).
To assess the reliability of this data, 161 women were re-interviewed a median of 3.5 months after the initial interview. The correlation between the 2 responses was high for adult weight (Pearson r = 0.96; p = 0.0001), height (Pearson r = 0.98; p = 0.0001) and birth weight (Pearson r = 0.95; p = 0.0001).
Table I shows the median adult BMI for the birth weight categories <2.3, 2.3<2.5, 2.5<3.2, 3.2<3.9, 3.9<4.5, and ≥4.5 kilograms. The median BMI was the greatest among those women in the <2.3 kg and ≥4.5 kg birth weight groups (26.6 kg/m2 in both) and lowest (24.4 kg/m2) in the 2.3<2.5 kg group. The relationship between birth weight and adult BMI was described by a nonlinear quadratic function [BMI = α + β1(Bwt) + β2(Bwt2)] (p = 0.0002).
|Birth weight (kg)||No. of subjects||%||Median adult BMI||Age-adjusted odds ratio of having BMI ≥30 vs. <25||95% confidence interval||p-value|
|2.3 < 2.5||140||7.6||24.4||0.90||0.55–1.47||0.67|
|2.5 < 3.2||700||37.8||25.1||1.00|
|3.2 < 3.9||556||30.0||25.5||1.17||0.86–1.57||0.33|
|3.9 < 4.5||246||13.3||25.4||1.17||0.80–1.72||0.43|
The odds ratio for obese (≥30 kg/m2) vs. normal (<25 kg/m2) adult BMI was also calculated for each birth weight category using the 2.5<3.2 kg group as the referent category. The results are summarized in Table I and Figure 1. The lightest and heaviest birth weight categories were associated with the greatest odds of being obese. Women weighing 4.5 kg or more at birth were nearly 2 times more likely (OR = 1.99, 95% CI 1.13–3.48) to be obese as adults. An excess in obesity was also observed among women who were underweight (<2.3 kg) at birth (OR = 1.67, 95% CI 1.01–2.76).
These data suggest that both low birth weight and high birth weight are associated with a greater risk of obesity in adulthood. The results support the hypothesis that the intrauterine environment may be a factor in the development of obesity in later life, which in turn has been linked to several prominent cancers.
Previous studies have also shown relationships between birth weight and the risk of obesity in adolescence15 and at midlife.16, 17, 18, 19 In all previous research, risk of obesity or median BMI levels rose with increasing birth weight among those with an average or above average birth weight, a pattern consistently observed both in men16, 17 and in women.18, 19 Results suggest that maternal overnutrition,20, 21 genetic factors or possibly maternal diabetes,22, 23, 24 which are associated with high birth weight, may be determinants of obesity in the offspring in later life.
As in the present data, a few previous studies18, 19 have also shown higher levels of obesity (or increased BMIs) in those with low birth weight. In an analysis based on Nurses' Health Study,19 the authors noted a clear U-shaped relationship between birth weight and adult BMI, which was apparent regardless of genetic background (as indicated by maternal adiposity). The pattern of higher risk at low birth weight was not observed in a study of 4,300 Danish men conscripted for military service16 in whom the relationship of birth and adult weight was reported to be linear; however, it is not clear how the young age of the men and selection on general health (10% were excluded for asthma and other health problems) would have affected the relationship. An association of low birth weight and obesity in later life is also consistent with data on famine survivors in which maternal caloric deprivation during the first two trimesters of gestation was associated with higher rates of adult obesity in the offspring.12
Barker has proposed that fetal tissues are adapted to the intrauterine environment, permanently altering their structure and function.25 Such a mechanism may explain associations between low birth weight and several chronic diseases of adulthood, including cardiovascular disease,15, 26, 27 hypertension16, 17, 28 and non-insulin dependent diabetes.17, 29 Lissner et al. found that self-reported birth weight was inversely related to serum leptin levels in adulthood, controlling for age and BMI.30 This suggests that leptin resistance, a possible cause of obesity, may be established during fetal development. The positive relationship of higher birth weight with adult breast cancer may be attributable to several factors unrelated to its influence on adult body fatness, as birth weight may reflect intrauterine exposures that dictate the numbers of target cells at risk for malignant change.31
One limitation of our data was the absence of information on birth length and gestational age at birth. Adjustment of birth weight by these indices would more accurately classify fatness at birth and would therefore be expected to strengthen the relationship between birth weight and adult BMI. In our study, we were also unable to adjust for effects of genetics on the development of obesity, which may contribute to the association between higher birth weight and obesity, as information on mother's weight was not recorded. In the Nurses' Health Study,16 the association of birth weight and adult BMI was independent of maternal adiposity.
Additional research is needed to better understand how the intrauterine environment affects fetal development and how any adaptations to the environment may affect the development of obesity in later life. Because obesity is related to a large number of health problems including several prominent cancers, identifying early life risk factors for obesity may eventually contribute to the prevention of these common diseases.