Birth Weight and Lipids in a National Birth Cohort Study

Abstract

Objective-To investigate the association between birth weight and lipid levels in a 53-year-old birth cohort from England, Scotland, and Wales. Methods and Results-Lipid levels were obtained from nonfasting blood samples, collected at the most recent follow-up of the MRC National Survey of Health and Development, for 2559 men and women. Regression models indicated that in men, a 1-kg increase in birth weight was associated with a 0.13-mmol/L decrease (95% CI: Ϫ0.23, Ϫ0.01) in total cholesterol at age 53 years (Pϭ0.03), compared with a 0.02-mmol/L (95% CI: Ϫ0.11, 0.15) increase in women and a 0.06-mmol/L (95% CI: Ϫ0.15, 0.02) decrease in men and women combined. Adjustment for current height and body mass index (BMI) in men reduced the size of the relationship, with height being responsible for the reduction. Adult height and height at 2 and 4 years were significantly associated with total cholesterol in men and in men and women combined. The negative association between total cholesterol and birth weight was strongest among men with high BMI at age 53 years (Pϭ0.03 for test for interaction between birth weight and BMI). There was no significant association between birth weight and LDL or HDL cholesterol in men or women before adjustment, but there was a positive association with HDL in women. When both sexes were analyzed together, an association was seen after adjustment for current body size. No confounding of these findings with social class was observed in this study. Conclusions-Our results suggest that the small effect of birth weight on lipid levels at age 53 years has a limited public health impact. The findings suggest that childhood height growth may be more important than prenatal growth. Key Words: birth weight Ⅲ height Ⅲ body mass index Ⅲ cholesterol Ⅲ epidemiology H igh blood cholesterol is an important risk factor for cardiovascular disease 1 and may be programmed in early life. 2 According to Barker's fetal origins hypothesis, 2 impaired fetal growth that leads to changes in lipid metabolism is one explanation for the observed inverse associations between birth weight and other measures of size at birth and adult cardiovascular disease. 3,4 Results from studies relating markers of fetal growth to adult lipid levels have, however, been inconsistent 3,5-9 and a recent meta-analysis estimated a decrease of only 0.05 mmol/L per 1 kg increase in birth weight. 10 To our knowledge, all except one study 7 of European adults 3,5,6,8,[11][12][13][14][15] have fewer than 800 subjects and may therefore have lacked the power to test for sex differences. Sex differences in the association between fetal growth and later coronary heart disease risk might be anticipated if fetal nutrition is the underlying mechanism because male fetuses grow at a faster rate, on average, than female fetuses. 16 However, discussion of sex differences based on separate analyses for males and females, without statistical tests of interaction, may result in an overemphasis of chance differences. 17 Adjustment of the birth weight effec...

Low Birth Weight Is Associated With Higher Adult Total Cholesterol Concentration in Men

“…Such sex differences have been reported before [7][8][9][10] and have been attributed to small numbers of female participants 7 (not a limiting factor in the BT cohort) and the premenopausal status of participating women. 9 Premenopausal women have lower TC concentrations than men of a similar age.…”

“…6 -10 Four of these studies reported regression coefficients: Ϫ0.19, Ϫ0.16, Ϫ0.25, and Ϫ0.15 mmol/L change in TC per 1-kg increase in birth weight (all adjusted for current weight or BMI). 6,7,9,10 The corresponding coefficient in BT men was Ϫ0.09 mmol/L per 1 kg. It is possible that the smaller effect size observed in BT men arose from the use of self-reported birth weight (the 4 comparison studies used medical records).…”

“…12 A recent systematic review of the literature on birth weight and blood cholesterol level concluded that there was only a weak association between low birth weight and higher TC. 13 Interestingly, a number of studies, including the 3 largest studies to publish findings relating birth weight to TC levels, 6,8,10 have reported sex differences in the association between birth weight and TC. These studies consistently found a strong association between lower birth weight and high cholesterol in men but weak or no association in women.…”

Intrauterine, Environmental, and Genetic Influences in the Relationship Between Birth Weight and Lipids in a Female Twin Cohort

“…4,6 The association between total cholesterol and birth weight is reported to be stronger for men than women; and the positive relationship between birth weight and high-density lipoprotein (HDL) is most apparent in postmenopausal women. 7,8 Where associations have been shown between birth weight and lipids, it remains unclear whether these might be a direct effect of undernutrition or caused by confounding as a result of parental factors. The association may also be mediated by a shared genetic mechanism.…”

No difference in the association between birth weight and total cholesterol for males and females. A SHARP (Scottish Heart and Arterial Disease Risk Prevention) study

“…2 A further large study published since this review, in contrast, found an association in females but not males and when these results were incorporated into the meta analysis the original sex difference was 'abolished'. 3 Despite over 30 publications reporting regression coefficients separately for men and women there have been only five large (>1000 individuals) [2][3][4][5][6] such studies in adults. In addition, some studies have used recalled birth weight or had limited data on potential confounding factors that could impact total cholesterol levels in adult life.…”