articleEstimated birth weight and adult cardiovascular risk factors in a developing southern Chinese population : a cross sectional study

Background: Birth weight is negatively associated with cardiovascular diseases and diabetes, but the associations are less well-established in developing populations where birth weight is often unavailable. We studied the association of birth weight and cardiovascular risk, using birth rank as an instrumental variable, in Southern China. Methods: We used published data on birth weight by birth rank from an appropriate population and baseline data from the Guangzhou Biobank Cohort Study phases 2 & 3 (2005-8) to examine the adjusted associations, using instrumental variable analysis, of birth weight with clinically measured cardiovascular risk factors and the metabolic syndrome in older (≥ 50 years) men (n = 5,051) and women (n = 13,907). Results: Estimated birth weight was associated with lower blood pressure (systolic -0.25 mm Hg 95% confidence interval (CI), -0.53 to 0.03 and diastolic -0.33 mm Hg 95% CI -0.48 to -0.18 per standard deviation higher birth weight), but had little association with glucose, lipids, waist-hip ratio, body mass index or the metabolic syndrome, adjusted for age, sex, early environment and number of offspring. Conclusion: Birth weight may impact blood pressure; however associations of birth weight with other cardiovascular risk factors may not be related to foetal exposures, but speculatively could be an historical co-incidence, with corresponding implications for prevention. Background Lower birth weight is associated with higher risk of cardiovascular diseases (CVD) [1,2], hypertension [3], diabetes [4,5], and perhaps poor lipids in adulthood [6,7], although maternal diabetes in pregnancy and fetal over growth may also be implicated in diabetes [8]. Moreover some of the effects are fairly small, and the underlying causative exposure(s) and mechanism(s) driving the association between lower birth weight and adult cardiovascular diseases are not, as yet, fully understood, possibly because other aspects of fetal development, such as body composition at birth [9], are more important. Maternal adiposity may contribute to higher birth weight [10]. Perhaps because of the difficulty of manipulating birth weight [11], as well as potential ethical problems, almost all the evidence concerning humans comes from observational studies, which may be inherently open to uncontrollable biases. There are many experimental animal studies investigating the impact of pre-natal under-nutrition on CVD risk, whether these generalize to humans, where maternal supplementation has little effect on CVD risk [12], remains unclear [13], although the effects of over-nutrition may be clearer [14,15]. Moreover, most of these observations come from studies in long-term industrialised populations, where it is difficult to disentangle the effects of birth weight from its social context including previous inter-generational exposures and subsequent exposures across the life course, including growth and final size. In developing populations birth weight is typically lower than in long-term industrialised countries, and thus may be a relatively more important contributor to the growing epidemic of non-communicable chronic diseases, and hence also an important intervention target. However, there is increasing evidence that some associations between life course exposures and car* Correspondence: hrmrlth@hkucc.hku. hk 1 School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Full list of author information is available at the end of the article BioMed Central © 2010 Schooling et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Schooling et al. BMC Public Health 2010, 10:270 http://www.biomedcentral. com/1471-2458/10/270 Page 2 of 14 diovascular disease or its risk factors are epidemiological stage specific [16-18], perhaps because of epigenetic influences, making evidence from non-western settings valuable for developing effective interventions. In developing populations birth weight, was not until recently, routinely measured and evidence concerning the association of birth weight with adult cardiovascular disease or its risk factors is mainly based on young people [18] or on small samples of inevitably atypical, hospital births with high attrition rates [18-22]. Given the long latency period following up a new cohort today could take decades to produce any evidence. In addition, associations between birth weight and cardiovascular disease or its risk factors may only be evident in adulthood or may amplify with age, making associations observed in childhood difficult to interpret. Using birth rank as an instrumental variable for birth weight provides an alternative approach to observational studies for elucidating the contribution of birth weight to adult cardiovascular disease in general. Such an approach also provides a means of assessing the association in developing populations within a reasonable time frame. Birth rank has been observed to be consistently associated with birth weight in many different settings at various epidemiological stages [23-30]. On the other hand there is little reason to believe that birth rank is causally associated with cardiovascular disease or its risk factors [31,32]. To clarify the association of birth weight with cardiovascular disease risk factors in general and outside of long-term developed western settings, we used birth rank as an instrumental variable in a large study of older southern Chinese. Methods Sources of data The Guangzhou Biobank Cohort Study is a collaboration amongst the Guangzhou No. 12 Hospital, the Universities of Hong Kong and Birmingham, and has been described in detail [33]. Recruitment of participants draws from "The Guangzhou Health and Happiness Association for the Respectable Elders", a community social and welfare association unofficially aligned with the municipal government where membership is open to anyone aged 50 years or older for a monthly, nominal fee of 4 Yuan (50 US cents). Recruitment for phase 2 took place from April 2005 to May 2006 and for phase 3 from September 2006 to January 2008. About 7% of permanent Guangzhou residents aged 50 years and over are members of "The Guangzhou Health and Happiness Association for the Respectable Elders", of whom 22% enrolled for phase 2 or 3 recruitment, constituting 65.9% of the total recruitment, and were included if they were capable of consenting, ambulatory, and not receiving treatment modalities which if omitted may result in immediate life threatening risk, such as chemotherapy or radiotherapy for cancer, or dialysis for renal failure. Participants underwent a halfday detailed medical interview, including disease history, and physical examination. In phases 2 and 3 the questionnaire was extended to include more questions concerning the participants' early life, including the question "How many children did your mother give birth to including you? And "How many of these were older than you"? The Guangzhou Medical Ethics Committee of the Chinese Medical Association approved the study and all participants gave written, informed consent before participation. The detailed methods of measurement have been reported [33]. In brief, standing height was measured without shoes to the nearest 0.1 centimetre. Weight was measured in light clothing to the nearest 0.1 kilogram. Hip circumference was measured at the greatest circumference round the buttocks below the iliac crest. Waist circumference was measured horizontally around the smallest circumference between the ribs and iliac crest, or at the level of the naval for obese participants. Body mass index (BMI) was calculated as the weight in kilograms divided by the square of height in metres. Seated blood pressure was recorded as the average of the last two of three measurements, using the Omron 705CP sphygmomanometer. Fasting HDL-cholesterol, triglyceride, total cholesterol and glucose levels were determined by the Shimadzu CL-8000 Clinical Chemical Analyzer. Instrumental variable The instrumental variable for birth weight was birth rank. We used published equations relating birth rank (of order 1 to 10+) to birth weight for 18,425 live born Chinese infants from poor families in Singapore from 1950 to 1951 [23]. This study represents 25% of all births in Singapore in the period, of which a summary is provided in Additional File 1 for easy reference. We used this source because it provides a large sample of Chinese from the relevant historic time. Moreover, the association between birth rank and birth weight is similar across populations, even though mean birth weight may differ. To illustrate this Figure 1 shows the association between birth rank and birth weight in the mid 20th century from a variety of locations, including Singapore [23-27]. In addition, we also repeated our analysis using the association between birth rank and birth weight from all these studies combined. In Singapore in the mid 20th century, the male infants were slightly heavier (mean birth weight 3.11 kilograms (kg), standard deviation (SD) 0.39) than the female infants (mean birth weight 3.03 kg, SD 0.37) [23]. Outcome measures We examined eight biological outcome measures, typically associated with cardiovascular disease: systolic Schooling et al. BMC Public Health 2010, 10:270 http://www.biomedcentral. com/1471-2458/10/270 Page 3 of 14 blood pressure, diastolic blood pressure, fasting plasma glucose, HDL-cholesterol, total cholesterol, triglycerides, waist-hip ratio (WHR), and body mass index (BMI). We also examined the metabolic syndrome and its components using the International Diabetes Federation definition [34], with raised blood pressure as systolic blood pressure ≥ 130 mmHg or dias