Birthweight, body-mass index in middle age, and incident coronary heart disease

doi:10.1016/S0140-6736(96)03482-4

The Lancet

Volume 348, Issue 9040, 30 November 1996, Pages 1478-1480

https://doi.org/10.1016/S0140-6736(96)03482-4 Get rights and content

Summary

Background

Several studies have shown a relation between fetal development, as shown by birthweight, and later coronary heart disease. This study investigated whether this relation is predominantly the consequence of early life exposures, or can best be explained in terms of an interaction between influences in early life and in adulthood.

Methods

This prospective study in Caerphilly, South Wales, included 1258 men, aged 45–59 at initial screening, who were able to provide birthweight data. These men are from an initial cohort of 2512 men, from whom information has been obtained in a series of examinations since 1979 on health-related behaviours, incidence of coronary heart disease, and risk factors. The main outcome measure was fatal and non-fatal coronary heart disease during 10 years of follow-up.

Findings

Higher birthweight was related to lower risk of coronary heart disease during the follow-up period: coronary heart disease occurred in 46 (11·6%) men in the lowest birthweight tertile, 44 (12·0%) of those in the middle tertile, and 38 (9·1%) of those in the highest tertile (p=0·03). Stratification of the cohort by body-mass index (BMI) revealed a significant interaction such that the inverse association between birthweight and risk of coronary heart disease was restricted to men in the top tertile of BMI (interaction test p=0·048 adjusted for age, and p=0·012 fully adjusted). Within the top BMI tertile, coronary heart disease occurred in 19 (16·4%) of men in the lowest birthweight tertile, 13 (12·6%) of those in the middle tertile, and 13 (7·5%) of those in the highest tertile (p=0·0005). These associations were not changed substantially by adjustment for age, father's social class, own social class, marital status, fibrinogen and cholesterol concentrations, systolic blood pressure, and smoking history.

Interpretation

The association between birthweight and risk of coronary heart disease cannot be explained by associations with childhood or adulthood socioeconomic status. Nor do conventional risk factors for coronary heart disease in adulthood account for the association. However, there is an important interaction between birthweight and BMI such that the increased risk of coronary heart disease associated with low birthweight is restricted to people who have high BMI in adulthood. Risk of coronary heart disease seems to be defined by the combined effect of early-life and later-life exposures.

Introduction

Several studies have shown an inverse association between birthweight and prevalence and mortality of coronary heart disease in adult life.1, 2 Although other studies have not confirmed this finding,³ it appears generally robust. Respiratory function, blood pressure, fat distribution, propensity to non-insulin-dependent diabetes, and blood fibrinogen concentrations are associated with birthweight in such a way as to generate the observed relations between birthweight and coronary heart disease.¹ There is, however, evidence that low birthweight–which is associated with adverse environmental conditions around the time of birth–is itself associated with social and biological exposures in later life.⁴ The interaction between fetal development, as indexed by birthweight, and factors acting in later life may be the crucial influence in the production of adverse cardiovascular-disease risk profiles. Leon and colleagues⁵ found that the inverse associations of birthweight with glucose tolerance and with blood pressure were most pronounced among people with high body-mass indices (BMI) in adulthood.⁵ We have previously shown an inverse association between birthweight and coronary heart disease in a cohort from South Wales, for whom information is recorded on early-life socioeconomic experience, biological, behavioural, and socioeconomic risk factors in middle age, and subsequent 10-year incidence of coronary heart disease.6, 7

We have investigated whether the relation between birthweight and coronary heart disease depends on adult BMI in the way that has been suggested for the associations of birthweight with blood pressure and with glucose tolerance.

Section snippets

Methods

2512 (89%) of 2818 men aged 45–59 living in a defined area of the town of Caerphilly and surrounding villages in South Wales were examined between 1979 and 1983. Information on health-related behaviours and existing coronary heart disease was obtained by questionnaire, together with measurements of height and weight, blood pressure, electrocardiography (ECG), and fasting blood samples. Total cholesterol, triglyceride, high-density-lipoprotein (HDL) cholesterol, glucose, fibrinogen, and insulin

Results

The cumulative incidence of coronary heart disease decreased with birthweight (table 1), but the decline was significant only for the men in the top tertile of BMI in adulthood. The association of birthweight and coronary heart disease by BMI tertile, before and after adjustment for potential confounders, is given in table 2, together with tests of interaction between birthweight and BMI. Significant interactions were seen, such that the association between birthweight and cumulative incidence

Discussion

This study was able to examine whether the associations between birthweight and future coronary heart disease depend on later-life factors or show interactions with these factors. We found that the relation between birthweight and coronary heart disease does not depend on association between birthweight and a large array of social and biological factors in middle age. However, in keeping with a study of the association of birthweight with adult glucose tolerance and blood pressure,⁵ we found

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Birthweight, adult risk factors and incident coronary heart disease: the Caerphilly Study
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Birthweight, breastfeeding and the risk of coronary heart disease in the Nurses' Health Study
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In a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class.
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This article is a report of a 2-day workshop, entitled “Social determinants of health and obstetric outcomes,” held during the Society for Maternal-Fetal Medicine 2022 Annual Pregnancy Meeting. Participants’ fields of expertise included obstetrics, pediatrics, epidemiology, health services, health equity, community-based research, and systems biology. The Commonwealth Foundation and the Alliance of Innovation on Maternal Health cosponsored the workshop and the Society for Women’s Health Research provided additional support. The workshop included presentations and small group discussions, and its goals were to accomplish the following:
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  Review the current evidence on the relationship between social determinants of health and obstetrical outcomes
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  Discuss approaches to and research opportunities for the epidemiologic analysis of social determinants of health in obstetrical settings
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Synthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1–2 spot samples during pregnancy and limited diversity of populations.
To study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program.
While many associations were modest and statistically imprecise, a 1-unit increase in log₁₀ pregnancy averaged concentration of benzophenone-3 and methylparaben were associated with decreases in birthweight, birthweight adjusted for gestational age and SGA. Increases in the odds of being SGA were 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%), respectively. Bisphenol S in third trimester was also associated with SGA (OR 1.52, 95% CI 1.08, 2.13). Associations of benzophenone-3 and methylparaben with PTB and LBW were null. In addition, a 1-unit increase in log₁₀ pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: −67%, −2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: −53%, 8%).
In a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life.
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Low birth weight has been associated with a greater risk of cardiovascular disease (CVD). However, the interaction between low birth weight and adult lifestyle factors on the risk of CVD remains unclear.
We included 20,169 men from the Health Professionals Follow-up Study (HPFS, 1986–2016), 52,380 women from the Nurses’ Health Study (NHS, 1980–2018), and 85,350 women from the Nurses’ Health Study II (NHS II, 1991–2017) in the USA who reported birth weight and updated data on adult body weight, smoking status, physical activity, and diet every 2–4 years. Incident cases of CVD, defined as a combined endpoint of fatal and nonfatal coronary heart disease (CHD) and stroke, were self-reported and confirmed by physicians through reviewing medical records.
During 4,370,051 person-years of follow-up, 16,244 incident CVD cases were documented, including 12,126 CHD and 4118 stroke cases. Cox proportional hazards regression models revealed an increased risk of CHD during adulthood across categories of decreasing birth weight in all cohorts (all P for linear trend <0.001). Additionally, we found an additive interaction between decreasing birth weight and unhealthy lifestyles on the risk of CHD among women, with a pooled relative excess risk due to interaction of 0.06 (95% CI: 0.04–0.08). The attributable proportions of the joint effect were 23.0% (95% CI: 11.0–36.0%) for decreasing birth weight alone, 67.0% (95% CI: 58.0–75.0%) for unhealthy lifestyle alone, and 11.0% (95% CI: 5.0–17.0%) for their additive interaction. Lower birth weight was associated with a greater stroke risk only among women, which was independent of later-life lifestyle factors.
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It is possible that those born small due to genetic or environmental factors may be especially vulnerable to an adult environment of nutritional excess that increases CVD risk [28]. Consistently, an early prospective study including 1258 men aged 45–59 observed an interaction between birth weight and adult BMI on the risk of CHD [29]. In addition, the Nurses’ Health Study including 66,111 female nurses found that the inverse association between birth weight and CHD was especially strong among heavier women [10].
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ArticlesBirthweight, body-mass index in middle age, and incident coronary heart disease

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Lancet

Public Health

J Nutr

Mothers, babies, and diseases in later life

Birthweight, breastfeeding and the risk of coronary heart disease in the Nurses' Health Study

Am J Epidemiol

Articles
Birthweight, body-mass index in middle age, and incident coronary heart disease