Hypertension and type 2 diabetes are obesity-related disorders. An early and consistent finding in human studies was that at any level of adult body mass index (BMI), men and women of lower birthweight had a higher risk of disease, or higher risk markers, such as insulin resistance (Fall et al. 1995
). In other words, people of lower birth weight behave as if they are more obese than their adult BMI would indicate. There has thus been considerable interest in whether low birth weight is associated with a more adipose adult body composition (Oken and Gillman 2003
, Rogers et al. 2003
, Wells et al. 2007
, Taylor and Poston 2007
Some populations are at particularly high risk of both low birth weight and adult obesity-related disease. For example, Indians and other South Asians have a low mean birth weight, thought to be due to poor maternal nutritional status and small maternal size. They also have a high risk of type 2 diabetes, which develops at a younger age, and lower mean BMI, than in white Caucasian populations. Their high risk has been partly attributed to a characteristic adult Indian phenotype of low muscle mass, increased percentage body fat and central adiposity (Yajnik 2004
). It is now known that this phenotype is present in Indian newborns at birth (Yajnik et al. 2003
) () and tracks through childhood (Krishnaveni 2005
). African-Americans, another high-risk group for low birth weight and adult chronic disease, have a similar ‘fat preserving’ newborn phenotype (Singh et al. 2010
The muscle-thin but adipose (‘thin-fat’) Indian newborn
Some of the earliest evidence for the intra-uterine programming of adiposity by fetal under-nutrition came from the Dutch Famine (‘Hunger Winter’) of 1944-45. Among 300,000 19-year old men entering military service, those whose mothers lived in famine-affected areas of the Netherlands during early pregnancy, had an increased risk of obesity compared to men whose mothers lived in non-famine areas (2.7% versus 1.5%) (Ravelli et al. 1976
, ). Obesity was defined as a body weight for height 120% or more greater than the WHO reference standard. Men whose mothers were exposed to famine in late pregnancy or in the early post-natal period had lower rates of obesity. A more recent study of 700 Dutch adults showed that women whose mothers were exposed to the Famine in early gestation had an increased mean BMI (7.4% higher [95% CI 0.7%, 14.5%]) and waist circumference (5.7 cm [95% CI 1.1 cm, 10.3 cm]) compared with controls born before or conceived after the Famine (Ravelli et al. 1999
). A study of men and women who were in utero during the much more prolonged famine that accompanied the Siege of Leningrad in 1941-44 showed no effects on BMI or waist measurements, though there was an increase in the subscapular/triceps skinfold ratio in women (Stanner et al. 1997
The prevalence of obesity among young Dutch men whose mothers were exposed or unexposed to famine during pregnancy
Such ‘experiments of history’ are rare, and although recent studies have started to investigate body composition in children of women who took part in RCTs of nutritional interventions in pregnancy (see below), most studies investigating the programming of body composition in humans have been observational, and have used birth weight as a proxy for fetal nutrition.
Birth weight and later body mass index
Many studies have examined the association between birth weight and later BMI (Rogers et al. 2003
), and have shown a small but consistently positive
relationship (r=0.1-0.2; β=0.2-0.7 kg/m2
per kg increase in birth weight) (). Although some studies, especially in larger cohorts, have shown a slightly J-shaped relationship, with an upturn in mean adult BMI in the lowest birth weight categories (Curhan et al. 1996
, Parsons et al. 2001
), this is a small effect. In summary, it is clear that lower birth weight individuals do not develop more hypertension and diabetes because they are more obese, as defined by BMI.
Adult body mass index according to categories of birth weight among Hertfordshire men aged 60-70 (n=845)
Birth weight and lean and fat mass
BMI is used to define obesity because it is easy to measure, but it has the major disadvantage that it does not distinguish between fat and fat-free mass, tissues that have very different effects on health. Recent studies have therefore attempted to examine the relationship of birth weight to fat and fat-free or lean mass (). The variety of methods used, and differences in the age of the subjects, sample size, and statistical approaches, makes comparison between studies difficult. However, almost all have found a positive association between birth weight and fat-free or lean mass in childhood or adult life. Studies that have adjusted for height show that this association does not simply result from the strong positive relationship of birth weight to later height. In contrast, these studies show inconsistent relationships between birth weight and later body fat. There was a positive association in 6 out of 18 studies that measured fat mass (), no association in 11, and an inverse association in only one study. After adjusting for current BMI or weight, one of these 18 studies and one additional study showed an inverse association between birth weight and fat mass, suggesting that at any current body weight, lower birth weight individuals had a higher fat mass. However, percentage body fat or the ratio of fat to lean mass showed no association with birth weight in 9 out of 11 studies with this outcome. It can be concluded from these studies that lower birth weight individuals tend to be ‘thinner’ in terms of overall body mass, and to have a lower lean body mass, but do not have an increased fat mass or percentage body fat.
Studies relating birth weight to later body composition in a) adults and b) children
Birth weight and central adiposity
Increased central (or abdominal) fat deposition carries a particularly high cardio-metabolic risk. Studies relating birth weight to anthropometric measurements of central adiposity, such as waist circumference, waist/hip ratio or truncal/peripheral skinfold ratios, initially suggested that lower birthweight was associated with greater abdominal and/or truncal adiposity in later life (Law et al. 1992
, Barker et al. 1997
, Okosun et al. 2000
, Byberg et al. 2000
). With the accumulation of more studies, the evidence for this from anthropometric data was not impressive (). Birth weight was either positively related or unrelated to later waist circumference and waist hip ratio in most studies. After adjusting for current BMI or weight, some studies showed that lower birth weight, especially in women, was associated with higher waist/hip ratio. More consistently, several showed a higher subscapular/triceps skinfold (SS/TR) ratio in people of lower birth weight (). However, the relevance of a high SS/TR for disease risk is unclear.
Recent studies have used better methods to assess abdominal adiposity, including ultrasound, CT, DXA and MRI (). For example, Rasmussen et al.
compared body composition between low birth weight (LBW, <10th
percentile) and normal birth weight men (50th
percentile) in a small selected sample (N=74) of Danish men aged 19-23 years, using DXA (Rasmussen et al. 2005
). Trunk and abdominal fat were examined separately. Abdominal fat mass was higher, abdominal lean mass lower, and the ratio of abdominal to total body fat higher, in the LBW group. A contrasting study, the largest to use imaging to assess body fat, was a DXA study of over 6000 UK children aged 9-10 years, from the population-based ALSPAC cohort (Rogers et al. 2006
). Birth weight was positively related to total body lean mass index and fat mass index, but not their ratio, and positively related to trunk fat. There was no association between birth weight and the ratio of trunk to total body fat. Differences between this study and the Danish study above were the sample size and selection, and the age of the subjects. The UK study did not separate abdominal fat from the rest of the trunk fat, and all the analyses were adjusted for the children’s height.
Out of 12 studies of truncal or abdominal adiposity using scan methods (5 in adults and 7 in children, ), 4 showed an inverse association between birth weight and truncal or abdominal fat mass, and one more showed an inverse association after adjusting for current BMI. One of these, and three additional studies, showed that lower birth weight was associated with a higher ratio of trunk fat to total body fat. Of the remaining 4 studies, 3 showed no associations between birth weight and truncal fat, and 1 (the largest, Rogers 2006
) showed a positive association. Overall, therefore, there is evidence in some populations that lower birth weight individuals have more abdominal fat, and/or more abdominal fat relative to total body fat. There is a need for more and larger studies, and for studies in different populations (all but one of the 12 studies were in white Caucasians and high income settings).
Maternal under-nutrition and adiposity
As already described, the Dutch famine studies showed that acute maternal under-nutrition in early pregnancy was associated with an increased risk of obesity in the offspring as young adults. Maternal under-nutrition in rodent experiments is also associated with increased adiposity in the offspring. Few of the animal studies have examined the effect of restoring nutrition to these under-nourished mothers. Several long-term follow-up studies of children born to under-nourished mothers taking part in randomised trials of nutritional interventions in pregnancy have recently been published. If maternal under-nutrition during pregnancy is a cause of increased adiposity in the offspring, we might expect to find evidence of ‘better’ body composition (more lean mass and less fat) among children born to mothers in the intervention groups than to control mothers.
Two trials were of protein-energy supplementation. In the Gambia, women received a daily high energy biscuit (energy 4250 KJ, protein 22 g) either from 20 weeks of pregnancy (intervention group) or during lactation (controls). The intervention influenced fetal nutrition, increasing birthweight by 136 g, reducing the incidence of low birthweight by 40%, and halving perinatal mortality. However, there were no differences in BMI, or in total and trunk body fat percentage (measured using bio-impedance) in the children at 11-17 years of age (Hawkesworth et al. 2008
). Among adolescents in India, whose pregnant mothers received food-based energy and protein supplements as part of a package of public health interventions, insulin resistance and arterial stiffness were reduced compared to controls, but there was no difference in adiposity (skinfolds) compared with children of unsupplemented mothers (Kinra et al. 2008
In animal models, maternal micronutrient deficiency, including deficiencies of iron, zinc, calcium and magnesium, has been associated with increased adiposity in the offspring (reviewed in Christian and Stewart 2010
). Three recent studies have reported body composition outcomes in children born during trials of maternal micronutrient supplementation. Two of these, in Nepal, used multiple micronutrients and both showed an increase in birth weight in the intervention group (Vaidya et al. 2008
, Stewart et al. 2009
). Vaidya et al. followed up children at the age of 2 years whose mothers received either multiple micronutrient supplements (intervention group) or routine iron and folic acid tablets (controls) during the second and third trimesters of pregnancy (Vaidya et al. 2008
). Children of women in the intervention group had larger head (2·4 mm [95% CI 0·6–4·3]) and mid-upper arm circumferences (2·4 mm [1·1– 3·7]) and larger triceps skinfold thickness (2·0 mm [0·0–0·4]) at 2 years, but lower systolic blood pressure (2·5 mm Hg [0·5–4·6]). In the other trial, women were randomised into 4 groups: 1) vitamin A alone (controls), and vitamin A plus 2) iron and folic acid, 3) iron, folic acid and zinc, and 4) multiple micronutrients including iron, folic acid and zinc. At 6-8 years of age, the children of mothers who received vitamin A, iron, folic acid and zinc were taller and less adipose (had thinner skinfolds) than children of control mothers (Stewart 2009
, ). There were no differences in waist circumference or BMI, and there were no effects on adiposity in the other supplementation groups. In the third trial, infants of mothers who were supplemented with iron, folic acid and zinc were heavier and had larger calf muscle area than those of women who received iron and folic acid without zinc (Iannotti et al. 2008
). There were no differences in adiposity, measured using skinfolds.
Figure 7 Differences in triceps skinfold thickness (TSF), subscapular skinfold thickness (SSF) and arm fat area (AFA) among Nepali children aged 6-8 y whose mothers received supplements containing vitamin A and other micronutrients in pregnancy compared with the (more ...)
These studies provide some early evidence that altering the micronutrient intake of under-nourished human mothers during pregnancy affects growth and body composition in the children. It is noteworthy that all these trials took place in low- or middle-income countries, where rates of obesity, though rising, are relatively low and where the opportunity for accumulating adipose tissue is low, compared with high-income settings. This would tend to reduce any differences in adiposity between children from intervention and control groups. Also, these trials started supplementation after the diagnosis of pregnancy, and usually during the second trimester. If early pregnancy is a critical time for nutritional programming of adiposity (as suggested by the Dutch Famine studies) effects may be limited. However, longer follow-up of these trials would be helpful, and data are required from studies in other populations and of other interventions.