Birthweight predicts adult cardiovascular disorders: Population based cross sectional survey

Abstract Background Cardiovascular disease (CVD) is the primary cause of death in the developed‐countries and mostly in the poorer areas of the country, and in lower income‐groups. Hypothesis Birthweight predicts adult development of angina, coronary heart disease, stroke, and combination of all CVD. Methods The AusDiab is a cross‐sectional study of Australians aged 25 years or over. Data on age, sex, previous‐CVD, smoking‐status, alcohol‐intake, time‐spent on watching television and physical‐activity, total house‐income, dwelling‐type and education‐level were collected by interviewer‐ administered‐questionnaires. Results Four thousand five hundred and two had birthweights (mean (SD) of 3.4(0.7) kg). Females in the lowest birthweight‐quintile were at least 1.23, 1.48, 1.65, and 1.23 times more likely to have angina, CAD, stroke, and CVS compared to the referent group ≥3.72 kg with P = .123, .09, .099, and 0.176, respectively. Similarly, males in the lowest‐birthweight‐quintile were 1.23, 1.30, 1.39, and 1.26 times more likely to have angina, CAD, stroke, and CVS compared to the referent‐group ≥4.05 kg with P = .231, .087, .102, and .123, respectively. Females with low birth weight (LBW) were at least 1.39, 1.40, 2.30, and 1.47 times more likely to have angina, CAD, stroke and CVS compared to those ≥2.5 kg with P = .06, .19, .03, and .13, respectively. Similarly, males with LBW were 1.76, 1.48, 3.34, and 1.70 times more likely to have angina, CAD, stroke, and CVS compared to those ≥2.5 kg with P = .14, .13, .03, and .08, respectively. Conclusion there was a negative relationship between birth weight and angina, CAD, stroke, and the overall CVS. It would be prudent, to adopt policies of intensified whole of life surveillance of lower‐birthweight people, anticipating this risk.


| INTRODUCTION
The prenatal-environment of babies in the women womb is of para-  7 Geographical studies yielded the first indication that CVD may originate from prenatal live during intrauterine development. Barker DJ clearly found that variations in mortality from the disease across England and Wales were shown to correlate closely with past differences in death rates among newborn babies. 8 Subsequently, it was found that cardiovascular mortality in later life is related to LBW in men and women born in Hertfordshire, United Kingdom, between 1911 and1930. 9 This association between LBW and subsequent risk of CVD was confirmed by other studies from UK, USA, and Europe. [10][11][12][13][14][15][16][17][18][19][20] These studies, however, were performed in selected populations, based on geographical location, ethnicity, and/or professional status. None have looked at the phenomenon in a general adult population.
Some researchers had criticized the fetal origin hypothesis on grounds that many had obtained significant results after adjusting for current body weight and or that physical activity, smoking status, alcohol intake, family history, and socioeconomic status were not taken into consideration when examining relationships. [21][22][23][24][25] In addition, some results were not reported separately for females and males.
Taking these factors in consideration, we evaluated the relationship between birthweight and angina, CHD, and stroke in the general population.

| Participants
The AusDiab survey is a cross sectional study in which data were collected from a stratified sample of Australians aged 25 years or over, residing in 42 randomly selected urban and nonurban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. 26 At our instigation, questions about birthweight were added to the second round of the AusDiab study. Participants were asked to state what their birthweight was. Then, participants were asked about the accuracy of the stated birthweight. This was followed by a question about the source of their stated birthweight.

| Measurements
Detailed methodology of the AusDiab study had been discussed in a previous manuscript. 26 In brief, data on age, sex, previous CVD (angina, CHD, and stroke), smoking status, alcohol intake, time spent on watching television and physical activity, total house income, dwelling type, and education level were collected by intervieweradministered questionnaires. [27][28][29] All subjects attended a local screening venue and completed a series of questionnaires, physical examinations, and specific laboratory tests which examined diabetic status, cardiovascular risk factors, and kidney function. An interviewer-administered questionnaire was used to determine smoking status, alcohol consumption, leisure-time physical activity, and television viewing. Assessment of socioeconomic status was based on education, dwelling type, and income.
Participants self-reported their frequency and duration of physical activity during the previous week. Physical activity was measured by the Active Australia questionnaire, which asks respondents about their participation in predominantly leisure-time physical activities (including walking for transport). 30 These questions have been found to provide reliable and valid estimates of adult physical activity. 30 Total physical activity time was calculated as the sum of the time spent walking (if continuous and for ≥10 minutes) or performing moderate-intensity physical activity, plus double the time spent in vigorous-intensity physical activity. 31 Frequency of physical activity was calculated by summing the number of sessions of vigorous activity, moderate activity, and walking. Physical activity was categorized to reflect the current Australian public health recommendation for physical activity 31 as active (≥150 minutes/week across at least five sessions) and inactive (<150 minutes/week and/or fewer than five sessions).
Participants also self-reported the total time they spent watching television (TV) or videos in the previous week. This measure provides a reliable and valid estimate of TV time among adults. 32 The average hours watching TV per week were used to create three categories of TV viewing (0-7, 7.01-14, and >14 hours/week).

| Statistics
Characteristics of the study sample are described by numbers and percentages for categorical variables and mean (SD) for continues variables. Student t-test was used for normally distributed variables.
Logistic regression was used to assess the strength of the relationship of angina, coronary artery disease (CAD), stroke and all cardiovascular system abnormalities (CVS) to birthweight. Significance was considered at P < .05. We examined the relationships for each gender separately except when examined by BMI categories, data were combined for both sexes as the number were small. We adjusted for age, adjusted for age, and body mass and for various confounding factors that include body mass, physical activity (based on time spent on exercise and watching television), smoking status, alcohol intake, and socioeconomic status. Stata for windows package software, StataCorp, College Station, Texas 77845 was used for statistical analyses.

| RESULTS
Of the 7157 who responded to our questionnaire, 4502 (63%) reported information related to their birthweight.
(12) People who reported their birthweight were younger, with a mean (SD) age of 48 (12) vs 51 years for those who did not report The birthweight distribution of the participants, which ranged from 0.4 to 7 kg with a mean (SD) of 3.37 (0.7) kg their birthweight, P < .001. As shown in Figure 1 Table 1 shows proportions of angina, CAD and stroke by birthweight quintiles for females and males. In females with lowest birthweight quintile, the proportions with angina, CAD, stroke and all abnormalities (CVS) were, although was significant only for CAD (P = .036), higher than those of higher birthweight. In males with lowest birthweights quintile, the proportions for angina, CAD, stroke, and CVS were higher, but nonsignificant (P = .056), than those for higher birthweight. .123, respectively. These relationships increased or persisted with adjustments for potential confounding factors. In males with birthweight between 3.06 and 3.26 were at least risks for cardiovascular problems compared to referent group. These relationships persisted when stratified by body mass index as shown in Table 3. After adjustment for age and sex, people in the lowest birthweight quintile, (<2.8 and <3.06 kg for females and male, respectively), had higher risk for developing angina, CAD, stroke and CVS compared to the referent quintile group (≥2.81 and 3.06 kg for females and males, respectively) .
When we use the traditional definition of LBW (<2.5 kg), as shown in Table 4  The Ausdiab-birthweight is the first study of its kind to examine the effect of birthweight on the development of various chronic diseases in a representative adult population. We and others had shown that birthweight is inversely associated with CVD risk factors such as T A B L E 1 Proportion of angina, coronary artery disease, stroke, and combined cardiovascular system abnormalities (CVS) by birthweight quintiles raised blood pressure, dyslipidaemia, diabetes, and metabolic syndrome/glucose intolerance. [35][36][37][38][39][40][41][42][43][44] A research was carried on people from Aberdeen, 1950s-Prospective-Children-Cohort, during time when environmental conditions, as proved by low infant and mother death rates, were quite advantageous for both children and female. This research showed an inverse relationship between occurrence of CHD and CVA and their original weight at birth and the . 45 The risk was like that described for Swedish female and male population that were born during 1915 to 1929.
Among the 10 636 male during the study period, the hazard ratios for CHD fell with increasing birthweight size. 14,15 Many studies in both men and women in Europe, the United States, and India, reported similar association between LBW and CHD. These epidemiological, as well as ours, cohort studies have found a roughly 20% lower risk of CVD for every kilogram of higher birth weight. 46 The inverse associations observed between birth weight and CHD is not markedly changed by adjustment for adult BMI. 46 Although adjustment for BMI has little impact, stratification by BMI has indicated that birth weight and BMI may interact to predict risk of CHD. Weight gain increases the risk of CVD among all adults, but especially for those born small. Lube et al concluded that the acceleration of early infant weight gain may aggravate the effects of LBW.
Multiple interactions between hemodynamic and metabolic parameters foreshadow the clustering of cardiometabolic risk factors later in life. 47 The magnitude of the association was strong; it was independent of social class including educational level or income or type of inhabitant. 45 The associations between birth weight and cardiovascular mortality have been shown to be independent of socioeconomic status at birth and during adulthood and of known adult lifestyle influences that might confound them (eg, cigarette smoking, diet, and exercise). 12,13,48 Adult lifestyle, however, clearly adds to the effects of early life 12,49 ; for example, studies in Finland demonstrated that the highest incidence of CHD occurs among men who were thin at birth and also had low household incomes as adults. 49 The results of randomized trials of nutritional interventions in infancy have led to the hypothesis that relative undernutrition and slower infant growth benefit later CVD. 50,51 Various CVD may be.
In our study, people who did not respond to the questionnaire, and those who could not recall their birthweight, were older and had higher rates of diabetes than those who reported a birthweight. Hence, overstatement of an exacerbating effect of lower birthweights on glycemic dysregulation in our study group is unlikely. Among birthweight respondents it is reassuring that the mean birthweight of those who guessed their birthweight was similar to those who obtained their birthweights from medical records or from a family member. This was also the case in British Telecom study. 52  blood pressure values but also the highest blood pressure variability, independent of the increases in ambulatory blood pressure values. 57 Similarly, Lurbe et al disclosed a relationship between birth weight and ambulatory pulse pressure while seeking to advance knowledge about the possible associations between birth weight and cardiovascular risk. 58 They also, reported that the results showed a relatively aged phenotype of large-vessel function in the children with the lowest birth weights. These early alterations may be amplified throughout life and may contribute to the increased cardiovascular risk associated with LBW. 59  This phenomenon probably has more implications for the cardio-

| Limitations
The study was conducted among Australian people and the study used a self-recall questionnaire to obtain birthweight data. We opted for this method of obtaining birthweight as there are no readily available data banks of birthweights that cover the AusDiab study popula- There are several additional limitations to the present study. First, there are two major sources of bias, first, the responder bias where 37% of participants did not provide their birthweight in this survey and second, the recollection bias where there is no verification that birthweight data, we accurate. Also, there was no correction for the gestational age. In addition, there are no data on maternal fetal complications that may have influenced health of participants beyond birthweight alone. Another limitation is the relatively small number for a cross-sectional study and hence P value not always significant.