U-shaped relationship between birth weight and childhood blood pressure in China

There is a consensus that cardiovascular function and blood pressure are determined during childhood and continue into adulthood [1]. Childhood hypertension has been considered a strong predicative factor for hypertension in adulthood. In the Beijing blood pressure cohort study, by measuring the inter-vessel parameters, Liang et al. followed 1259 subjects (6–18 years old) over 24 years and found that children with elevated blood pressure had accelerated remodelling of both cardiac and arterial systems in early and middle adulthood [2]. Targeted organ damage, especially damage to the heart, was detectable in some hypertensive children [3]. Therefore, childhood hypertension should now be considered a public health concern in younger generations both in developed countries and in developing countries with rapid development.

Childhood blood pressure is affected both by genetic and environmental factors, including factors at birth (birth weight) and factors after birth (dietary structure, weight, physical activity) [4‐6]. Poor weight management and childhood metabolic syndrome have been demonstrated as some of the leading causes of abnormal blood pressure in children [7]. China is experiencing a huge increase in the prevalence of obesity among children and adolescents. Cao et al. first observed that the incidence of hypertension was 3.1% among teenagers (12–17 years old) in Changsha, and the risk of hypertension increased three- to four-fold once BMI reached above the 95th percentile [8]. Dong et al. explored the relationship between BMI and blood pressure in Chinese children. After statistical adjustment for BMI, the mean increase in SBP was reduced by 40.5%, which indicated that obesity was one of the leading determinants of high SBP [9]. Moreover, the residual increase suggested that some other important factors also contributed to childhood hypertension.

The developmental origins of health and disease (DOHaD) theory and the life course theory (LCT) lead to the hypothesis that nutritional status in utero may permanently change the body’s structure, function and metabolism in ways that cause chronic diseases in later life [10‐12]. There is some evidence showing that people born with high birth weight are at higher risk of developing cardiovascular diseases in later life [13]. Xie et al. collected cross-sectional data from 1253 female nurses aged 35–65 years and found a J-shaped relationship between birth weight and blood pressure in adulthood [14]. Launer et al. found that both low birth weight and high birth weight infants had a higher risk of elevated blood pressure [15]. However, the results from Chinese studies were quite inconsistent with the previous conclusions. When Zhai et al. analysed 18920 students aged 6–11 years, they found that elevated blood pressure in children and teenagers was associated only with BMI but not with birth weight [16]. Li et al. selected 1435 pairs of children with high or normal birth weight from a birth cohort between 1993 and 1995 in Wuxi and followed them until 2005 to 2007. They found no statistically significant relationship between high birth weight and blood pressure [17].

In the present study, we analysed data from a metabolic syndrome investigation among children and adolescents in six cities across China and adjusted for the influence of BMI and other confounders. We finally demonstrated the potential influence of birth weight on childhood blood pressure. The purpose of the current study was first to investigate the prevalence of hypertension in children and adolescents in China. Second and more importantly, we aimed to reveal the association between birth weight and childhood hypertension.

The current study examined the association between birth weight and childhood blood pressure by collecting school-based data from six Chinese cities. This study is also the first, to the best of our knowledge, to investigate the relationship between birth weight and childhood hypertension using a large census from urban areas in China. In summary, birth weight had a profound impact on childhood blood pressure and the prevalence of primary hypertension in Chinese children and adolescents. Moreover, the association between birth weight and blood pressure remained U-shaped after adjusting for various confounding factors, including BAZ, season of birth and area of residence. Children with birth weights from 2500 to 2999 g had the lowest blood pressure and lowest risk for childhood hypertension. Birth weight significantly influenced systolic blood pressure. However, its effect on diastolic blood pressure remains unknown.

Some of the previous studies suggested an inverse relationship between birth weight and childhood blood pressure, while others showed a positive relationship or no association at all. In 2012, Edvardsson et al. reviewed the existing studies and listed several reasons that might drive the results apart. They believed that inadequate adjustment for potential confounders, failure to use standard blood pressure values, and disparities in the target populations together contributed to the discrepant results [21]. The results from the current study verified a U-shaped relationship between birth weight and childhood blood pressure. The associations between birth weight and childhood blood pressure were not unidirectional, and this, to some extent, explained why neither the inverse nor the positive modelling was adequate to explain the true relationship in reality.

The proposed mechanisms linking birth weight and childhood hypertension have been widely studied. As has been shown in animal models and partly in humans, the hyperfiltration theory suggests that the reduction in nephron number, a decreased kidney mass and a reduction in renal reserve in low birth weight children enhance salt sensitivity and increase the risk of hypertension [22‐24]. The mechanism linking high birth weight to childhood hypertension was buried within the correlation between birth weight and current weight. Metabolic syndrome and obesity play important roles in the development of arterial stiffness and endothelial dysfunction [7, 25, 26]. However, as presented in this study, current weight or BAZ is not adequate to explain the increase in blood pressure. The Barker theory posits that cardiovascular diseases originate during intra-uterine development and that undernutrition in utero permanently changes the organ structure, function and systematic metabolism in ways that lead to cardiovascular events in later life [10]. Pietrobelli et al. further expanded the Barker hypothesis and suggested that intra-uterine nutritional status should be intervened upon artificially to avoid childhood obesity and coronary artery diseases in the future [27]. Hence, foetal programming needs to be studied more extensively to determine the underlying pathophysiological mechanisms. Of interest was that DBP was not influenced by birth weight, emphasizing the possibility of different mechanisms behind high SBP and high DBP in children and adolescents. Traditionally, DBP is considered the most important component of blood pressure. However, there are no studies on isolated DBP levels in either adults or children. In studies of the ageing population, SBP and pulse pressure (SBP - DBP) have been considered to be better predictors of cardiac risks [28]. The results here showed that BMI and birth weight influenced DBP but failed to explain its elevation above the normal range.

As even small increases in blood pressure are known to increase the long-term risk of cardiovascular diseases and hypertensive nephropathy, it is crucial to understand the aetiology of primary childhood hypertension and to look for potential precautions. Li et al. reported that the prevalence of abnormal blood pressure, together with obesity, dramatically increased from 1993 to 2013 in China [29]. Paediatric hypertension is usually asymptomatic, difficult to recognize by parents and can easily be missed by health professionals. Moreover, even pre-hypertension is not completely benign, and its rate of progression to hypertension is approximately 7% per year over a 2-year interval [3]. The relationship between birth weight and hypertension increases from childhood to adulthood [30]. According to the conclusions of this study, the prevention of primary hypertension may require more insight into foetal development and birth weight control in a reasonable range. In the era of precise medicine, it is promising to intervene in the risk factors during the gestational stage or early childhood. Prevention of cardiovascular diseases should begin in childhood by regularly screening for hypertension, counselling for healthy lifestyle habits and avoiding preventable risk factors.

In this work, the study population was well defined, and we used Chinese-specific standardized methods to collect data. The effects of main potential confounders, especially BAZ, were controlled in the analysis of covariance. However, the present study had limitations. This was a cross-sectional study, and there might be some recall bias in the interview results. Second, information on growth patterns was not collected. An increasing amount of evidence is available showing that birth weight can influence childhood growth velocity and influence blood pressure [31, 32]. Third, a lack of information on physical activity and the socioeconomic status of each family was collected. Researchers have found socioeconomic status to be an important risk factor both for birth weight and blood pressure [33, 34]. For the reasons mentioned above, well-designed prospective studies are urgently needed to examine infants and track their blood pressure into adulthood to verify the causal effect of birth weight on hypertension. Information about family history, physical exercise, pubertal development and socioeconomic status should be clearly recorded and taken into analysis.

This study revealed that birth weight was associated with blood pressure levels and the risk of hypertension in Chinese children and adolescents. Both low and high birth weight increased the risk of hypertension. Birth weight influenced SBP but had a minimal effect on DBP.