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Possible role of birth weight on general and central obesity in Chinese children and adolescents: a cross-sectional study
Annals of Epidemiology xxx (2015) 1e5
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Original article
Possible role of birth weight on general and central obesity in Chinese children and adolescents: a cross-sectional study Zhe-pin Yuan MD a,1, Min Yang MD b,1, Li Liang PhD c, Jun-Fen Fu PhD d, Feng Xiong PhD e, Ge-Li Liu PhD f, Chun-Xiu Gong MD g, Fei-Hong Luo PhD h, Shao-Ke Chen PhD i, Dan-Dan Zhang PhD j, Shuai Zhang MD j, Yi-Min Zhu PhD a, * a
Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, China Department of Nutrition and Food Safety, Zhejiang University School of Public Health, Hangzhou, China Department of Pediatrics, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China d Department of Endocrinology, Children’s Hospital of College of Medicine, Zhejiang University, Hangzhou, China e Department of Endocrinology, Children’s Hospital Affiliated to Chongqing Medical University, Chongqing, China f Department of Pediatrics, General Hospital of Tianjin Medical University, Tianjin, China g Department of Pediatrics, Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing, China h Department of Pediatric Endocrinology and Genetic Metabolic Diseases, Children’s Hospital of Fudan University, Shanghai, China i Department of Pediatrics Endocrinology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China j Department of Pathology, Zhejiang University School of Medicine, Hangzhou, China b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 4 November 2014 Accepted 8 May 2015
Purpose: According to the developmental origins of health and disease theory, fetal nutrition is associated with obesity and chronic diseases in children and adults. However, previous findings regarding the association between birth weight and childhood obesity have been inconsistent. The aim of the present study was to investigate the relationship between birth weight and childhood obesity in China. Methods: The 16,580 subjects (8477 boys and 8103 girls) aged 7e17 years, who participated in this study were recruited from a cross-sectional study in six cities in China. Epidemiological data, including birth information, were collected through face-to-face interviews, and anthropometric indices were measured by trained physicians. Overweight and obese cases were defined using sex-specific and agespecific 85th and 95th percentile body mass index (BMI) cutoffs for Han children and adolescents. Central obesity was defined using sex-specific waist-to-height ratio (WHtR) cutoffs (WHtR 0.48 in boys and WHtR 0.46 for girls). Results: The overall rate of overweight status and obesity was 20.3% in the Chinese children and adolescents and that of central obesity was 18.9%. Subjects were stratified into eight groups according to weight at birth. J-shaped relationships were observed between birth weight and BMI for age Z-score and WHtR. After adjusting for confounders such as gender, gestational age, parental factors, and dietary factors, the risk of overweight and obese status was still higher in the children with higher birth weights than in children with birth weights of 3000e3499 g (3500e3999 g: odds ratio [OR] ¼ 1.14, 95% confidence interval [CI] ¼ 1.02e1.28; 4000e4499 g: OR ¼ 1.39, 95% CI ¼ 1.19e1.63; and 4500e4999 g: OR ¼ 1.36, 95% CI ¼ 1.06e1.76). Moderately high birth weight also increased the risk of central obesity. Relative to the children with normal birth weights (3000e3499 g), the adjusted OR and 95% CI were 1.33 (1.13e1.56) in children with birth weights of 4000e4499 g. Children with very low birth weight (lower than 1500 g) had the highest risk of central obesity. The adjusted OR was 2.30 (95% CI: 1.03e5.14) relative to children with birth weights of 3000e3499 g. Conclusions: Birth weight was associated with obesity in Chinese children and adolescents. J-shaped relationships were observed between birth weight and BMI and WHtR in childhood, and very low birth weight was associated with a mild increase in the risk of central obesity in Chinese children and adolescents. Ó 2015 Elsevier Inc. All rights reserved.
Keywords: Birth weight Overweight/obesity Central obesity Childhood
The authors declare that they have no competing interest. * Corresponding author. Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, 866 Yu-hang-tang Road, Hangzhou, Zhejiang 310058, China. Tel.: þ86-571-88208138; fax: þ86-571-88208198.
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E-mail address: [email protected] (Y.-M. Zhu). These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.annepidem.2015.05.011 1047-2797/Ó 2015 Elsevier Inc. All rights reserved.
Please cite this article in press as: Yuan Zhe-pin, et al., Possible role of birth weight on general and central obesity in Chinese children and adolescents: a cross-sectional study, Annals of Epidemiology (2015), http://dx.doi.org/10.1016/j.annepidem.2015.05.011
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Z.-p. Yuan et al. / Annals of Epidemiology xxx (2015) 1e5
Background
Data collection and measurements
The prevalence of obesity in children has increased at an alarming rate in both developed and developing countries [1e4]. Childhood obesity is of particular concern because it has been widely reported to have adverse consequences on mortality and morbidity in adulthood [5e9].There has been an increasing focus that early life events might play an important role in childhood obesity [10e12]. The Developmental origins of health and disease (DOHaD) hypothesis, initially proposed by David Barker, states that poor fetal nutrition causes adaptations that increase future propensity to obesity, diabetes, and cardiovascular diseases [13,14]. Prenatal features, such as abnormal birth weight (low birth weight or high birth weight), which are used in many studies as proxies for fetal growth, might be directly associated with body mass index in childhood [12]. After this hypothesis, a number of epidemiological studies have examined the association between birth weight and later obesity. However, the results of previous works have been inconsistent. Curhan et al. [15] observed a U-shaped relationship in the Nurses’ Health Study I. This relationship was replicated in the Nurses’ Health Study II and another study on American women [16]. A study from China showed the incidences in obesity and overweight status in adolescence to be 33.3% in subjects with high birth weight and 38.9% in those with low birth weight, both significantly higher than in subjects with normal birth weight (16.2%) [17]. However, other investigators have been unable to show either high birth weight or low birth weight to be associated with an increased propensity for obesity [18e20]. Linear relationships (positive and inverse) have also been reported. For example, inverse relationships were found between birth weight and BMI, waist-hip ratio, and total abdominal fat [21e24]. However, other studies have suggested that birth weight is positively associated with BMI in later life [25e28]. For instance, Hirschler performed a study in Argentina, where she found high birth weight (HBW; birth weight 4000 g) to be associated with an increased risk of overweight status and obesity (OW/OB; odds ratio [OR] ¼ 2.48, 95% confidence interval [CI] ¼ 1.62e3.81) and metabolic syndrome (OR ¼ 3.16, 95% CI ¼ 1.38e7.24) and found low birth weight (LBW, birth weight <2500 g) to be a protective factor for OW/OB [25]. One study performed on Canadian children found that the risk of obesity increased with an OR of 1.05 (95% CI ¼ 1.00e1.09) for every 100 g of birth weight [26]. The differences in the results might be due to the different ranges of birth weight used in these studies. Owing to the limited sample sizes, previous studies did not examine the associations between different ranges of LBW with obesity. The aim of this study was to evaluate the relationship between birth weight and obesity using a relatively large-scale sample of Chinese children and adolescents.
Anthropometric measurements Anthropometric indices, including weight, height, and waist circumference (WC), were measured by well-trained investigators, after a standard protocol [29]. Height and weight were measured with the participants wearing light clothing and without shoes. WC was measured at the midpoint between the iliac crest and lowest rib. The anthropometric indices are here reported as the average of three repeated measurements. BMI was calculated as the individual’s body weight in kilograms divided by the square of his or her height in meters. Waist-to-height ratio (WHtR) was calculated as WC in centimeters divided by the height in centimeters.
Methods Subject The subjects in this study were recruited from a previous crosssectional investigation of metabolic syndrome in children and adolescents. This investigation was conducted in 2010 on the students aged 7e17 years in China and has been described in detail previously [29]. The study protocols were approved by the Research Ethics Committees at School of Public Health and Medical Ethics Committees at the Children’s Hospital of the Zhejiang University College of Medicine. All the participants and their guardians provided written informed consent.
Definitions Body mass index (BMI) was calculated as body weight divided by height squared (kg/m2), and WHtR was calculated as WC in centimeters divided by the height in centimeters. BMI was used for age Z-score (BAZ) to standardize the value of BMI across different ages and genders. Given a child’s age, gender, BMI, and an appropriate reference standard, a BMI Z-score could be calculated [30]. Here BAZs were established using BMI reference material issued by the World Health Organization 2007 (5e19 years) [31]. Overweight status was defined as body mass index (BMI) 85th percentile and <95th percentile of the BMI reference data for Han children and adolescents according to age and gender. Obesity was defined as BMI 95th percentile of the BMI reference data [32]. Central obesity was defined as WHtR is 0.48 or more in boys and WHtR is 0.46 or more in girls according to the definition of metabolic syndrome by Chinese Medical Association [33]. Subjects were divided into eight categories by birth weight: <1500 g, 1500e1999 g, 2000e2499 g, 2500e2999 g, 3000e3499 g, 3500e3999 g, 4000e4499 g, and 4500 g. Potential confounding factors Demographic variables including gender, age, gestational age, stage of pubertal development, area of residence, parental BMI, parental smoking status, food preference (meat-dominant diet, balanced diet, and vegetable-dominant diet), and salt intake (light salt, moderate salt, and heavy salt) were determined in face-to-face interviews with the participants and their parents. Stage of pubertal development was assessed using parents’ descriptions of their children’s secondary sex characteristics associated with the five standard Tanner stages [34,35]. Statistical analyses Normally distributed variables were expressed as means standard deviation and were compared using Student’s t test. Categorical variables are here expressed as frequencies (percentages); they were compared using c2 tests. Analysis of variance was used to compare BAZ and WHtR among different groups of birth weight. Binary logistic regression was used to analyze associations of birth weight with OW/OB and central obesity in childhood. All the tests were two sided, and results were considered significant at 0.05. Statistical analyses were performed using SPSS for Windows (SPSS 17.0 Inc., Chicago, IL). Results Subject characteristics Here, 16,580 subjects aged 7e17 years participated in this study. The demographic data and anthropometric variables of the subjects
Z.-p. Yuan et al. / Annals of Epidemiology xxx (2015) 1e5
stratified by gender are listed in Table 1. The boys had significantly higher levels of birth weight, weight, height, WC, BMI, BAZ, and WHtR than the girls (P < .001). The prevalence of OW/OB was 24.7% in boys, significantly higher than in girls (15.8%, P < .01). The prevalence of central obesity was 19.8% in boys, also significantly higher than in girls (18.0%, P < .01). There were no significant differences between boys and girls in gestational age at birth or area of residence (both P > .05). Relationships between birth weight with BAZ and WHtR Table 2 lists the associations of birth weight with BAZ and WHtR. There were J-shaped relationships (the highest point was at the end, and the lowest point was early in the curve) between birth weight with children’s BAZ and WHtR. Children with very low birth weight (VLBW <1500 g) had higher BAZ (0.43 1.38) than subjects in other groups, but the differences were not statistically significant (P > .05). Participants with lower birth weights (1500 g to 2999 g) had lower BAZ than those with birth weights of 3000e3499 g (average BAZ ¼ 0.21 1.10), but the difference was not statistically significant. Those with higher birth weights (3500 g) had higher BAZ, and the difference was statistically significant (P < .05). BAZ was positively related with birth weight for birth weights >1500 g (r ¼ 0.109, P < .001). The children with the highest birth weights (4500 g) had the highest BAZ (0.46 1.29). Although the children with VLBW had the highest value of WHtR (0.45 0.06) compared to other groups, the differences were also not statistically significant (P > .05). When birth weight between 3000 g and 3499 g was considered standard, higher birth weight (4000 g) was associated with higher WHtR (P < .05). Birth weight and the risk of OW/OB and central obesity The prevalence of OW/OB and central obesity in children among groups of different birth weights is shown in Table 3. J-shaped associations were found between birth weight and the prevalence of OW/OB and central obesity. The prevalence of OW/OB in children with VLBW was 17.0% (8 of 47), which was higher than in children with birth weights of 1500e1999 g, 2000e2499 g, and 2500e2999 g. The prevalence of central obesity was 25.5% (12 of 47) in children with VLBW, which was higher than in children in other groups. The prevalence of OW/OB was positively correlated with birth weight in all groups except the VLBW group. After adjusting for confounders such as gender, gestational age, age, stage of pubertal development, area of residence, parental BMI, parental smoking status, and child’s diet factors (food preferences and salt intake), higher birth weight increased the risk of childhood OW/OB compared to birth weight of 3000e3499 g (3500e3999 g: OR ¼ 1.14, 95% CI ¼ 1.02e1.28; 4000e4499 g: OR ¼ 1.39, 95% CI ¼ 1.19e1.63; 4500e4999 g: OR ¼ 1.36, 95% CI ¼ 1.06e1.76). Children with lower birth weights had a lower risk of OW/OB (1500e1999 g: OR ¼ 0.35; 95% CI ¼ 0.18e0.67; 2000e2499 g: OR ¼ 0.69, 95% CI ¼ 0.51e0.95; 2500e2999 g: OR ¼ 0.83, 95% CI ¼ 0.71e0.96). However, no statistically significant difference was found between children with VLBW and children with birth weights of 3000e3499 g with respect to risk of OW/OB. The risk of central obesity was higher in children with birth weights of 4000e4499 g (OR ¼ 1.33, 95% CI ¼ 1.13e1.56) than in children with birth weights of 3000e3499 g. Children with VLBW had the highest risk of central obesity (OR ¼ 2.03, 95% CI ¼ 1.03e5.14). A borderline association of birth weight with central obesity was found in children with birth weights of 2500e2999 g (OR ¼ 0.89, 95% CI ¼ 0.77e1.03), in children with birth weights of 3500e3999 g (OR ¼ 1.08, 95% CI ¼ 0.96e1.20), and in children with birth weights >4500 g (OR ¼ 1.22, 95% CI ¼ 0.95e1.59).
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Table 1 Basic characteristics of the subjects* Variables
Total
Boys
n ¼ 16,580
n ¼ 8477
Age (y), n (%) 11.6 2.6 11.6 2.6 7 1010 (6.1) 543 (6.4) 8 1518 (9.2) 799 (9.4) 9 1627 (9.8) 841 (9.9) 10 1937 (11.7) 997 (11.8) 11 1760 (10.6) 924 (10.9) 12 1862 (11.2) 971 (11.5) 13 2182 (13.2) 1054 (12.4) 14 2285 (13.8) 1135 (13.4) 15 1536 (9.3) 779 (9.2) 16 682 (4.1) 334 (3.9) 17 181 (1.1) 100 (1.2) Weight (kg) 41.9 14.3 43.1 15.5 Height (cm) 147.6 15.2 148.4 16.5 WC (cm) 63.3 10.4 64.7 11.2 y BMI (kg/m ) 18.7 3.6 18.9 3.8 BAZ 0.19 1.27 0.36 1.36 WHtR 0.43 0.05 0.44 0.06 Birth weight (g) 3341.0 636.3 3403.6 645.4 Gestational 38.6 4.2 38.6 4.3 age (wk) General obesity categoryz, n (%) Normal 13214 (79.7) 6388 (75.4) Overweight 1928 (11.6) 1184 (14.0) Obese 1438 (8.7) 905 (10.7) Central obesity category,x n (%) Normal 13429 (81.1) 6782 (80.2) Central obesity 3129 (18.9) 1673 (19.8) Birth weight category (g), n (%) <1500 47 (0.3) 23 (0.3) 1500e1999 180 (1.1) 93 (1.1) 2000e2499 508 (3.1) 227 (2.7) 2500e2999 2431 (14.7) 1036 (12.2) 3000e3499 6926 (41.8) 3273 (38.6) 3500e3999 4419 (26.7) 2523 (29.8) 4000e4499 1540 (9.3) 990 (11.7) 4500 529 (3.2) 312 (3.7) Area of residence, n (%) Urban 11332 (68.3) 5798 (68.4) Rural 5248 (31.7) 2679 (31.6) Chongqing 3535 (21.3) 1757 (20.7) Hangzhou 3158 (19.0) 1773 (20.9) Nanning 2612 (15.8) 1327 (15.7) Beijing 2705 (16.3) 1407 (16.6) Shanghai 1578 (9.5) 785 (9.3) Tianjin 2992 (18.0) 1428 (16.8) Stage of pubertal developmentk, n (%) 1 5022 (31.1) 3198 (38.9) 2 3004 (18.6) 1500 (18.3) 3 2976 (18.4) 1379 (16.8) 4 2378 (14.7) 737 (9) 5 1254 (7.8) 634 (7.7)
Py
Girls n ¼ 8103 11.7 2.6 467 (5.8) 719 (8.9) 786 (9.7) 940 (11.6) 836 (10.3) 891 (11.0) 1128 (13.9) 1150 (14.2) 757 (9.3) 348 (4.3) 81 (1.0) 40.7 12.8 146.7 13.7 61.8 9.4 18.4 3.4 0.02 1.14 0.42 0.05 3275.6 620.0 38.6 4.1
.006 .054
<.001 <.001 <.001 <.001 <.001 <.001 <.001 .890 <.001
6826 (84.2) 744 (9.2) 533 (6.6) .003 6647 (82.0) 1456 (18.0) <.001 24 87 281 1395 3653 1896 550 217
(0.3) (1.1) (3.5) (17.2) (45.1) (23.4) (6.8) (2.7)
5534 2569 1778 1385 1285 1298 793 1564
(68.3) (31.7) (21.9) (17.1) (15.9) (16.0) (9.8) (19.3)
1824 1504 1597 1641 620
(23) (19) (20.2) (20.7) (7.8)
.889 <.001
<.001
* All quantitative data are expressed as mean standard deviation, all qualitative are expressed as frequency (%). y P for t tests or c2 tests. z Defined as normal (BMI for age <85th percentile); overweight (BMI for age ¼ 85the95th percentile); obesity (BMI for age 95th percentile). x Defined as central obesity (WHtR 0.48 in boys or WHtR 0.46 in girls) and normal (WHtR <0.48 in boys or WHtR <0.46 in girls). k Assessed by parents’ description of their children’s secondary sex characteristics associated with the five standard Tanner stages.
Discussion In the present study, results showed J-shaped relationships between birth weight and BMI and WHtR. Results also showed that VLBW increased the risk of central obesity in Chinese children and adolescents. These findings confirmed previous results indicating an association between HBW and obesity in later life.
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Z.-p. Yuan et al. / Annals of Epidemiology xxx (2015) 1e5
Table 2 Relationships of birth weight with BAZ and WHtR Birth weight, g
<1500 1500e1999 2000e2499 2500e2999 3000e3499 3500e3999 4000e4499 4500
N
BAZ
32 142 411 1986 5614 3618 1266 428
Py
P*
Mean
SD
Estimated marginal means
0.43 0.21 0.11 0.02 0.14 0.34 0.44 0.46
1.38 1.10 1.30 1.25 1.27 1.25 1.28 1.29
0.39 0.28 0.12 0.01 0.12 0.26 0.38 0.40
z
WHtR
SE 0.21 0.10 0.06 0.03 0.02 0.02 0.03 0.06
.998 .003 .003 .001 d <.001 <.001 <.001
d .124 .447 .830 .998 1.000 1.000 1.000
Mean
SD
Estimated marginal means
0.45 0.42 0.43 0.42 0.43 0.43 0.44 0.44
0.06 0.05 0.05 0.05 0.06 0.06 0.06 0.06
0.44 0.42 0.42 0.42 0.43 0.43 0.44 0.44
z
P*
Py
.946 .999 1.000 .776 d .592 <.001 .030
d .714 .826 .789 .946 .994 1.000 1.000
SE 0.009 0.004 0.003 0.001 0.001 0.001 0.002 0.003
SD ¼ standard deviation; SE ¼ standard error. * Based on estimated marginal means; adjustment for multiple comparisons: Sidak; reference: birth weight between 3000 g and 3499 g. y Based on estimated marginal means; adjustment for multiple comparisons: Sidak; reference: birth weight between 1500 g and 1999 g. z Adjusted for gender, gestational age, age, stage of pubertal development, area of residence, parental BMI, parental smoking status (both nonsmokers, one smoker, and both smokers), and diet factors such as food preference (meat-dominant diet, balanced diet, and vegetable-dominant diet) and salt intake (light, moderate, and high).
(1500e2999 g) had less risk of obesity and central obesity, and children with VLBW (<1500 g) had no visible difference from children of ordinary birth weight with respect to the risk of obesity, but had a higher risk of central obesity. This indicated that prior findings of a positive relationship between LBW and central obesity could be largely attributable to long-term adverse effects caused by VLBW. These findings also confirmed the positive relationships between HBW and obesity and central obesity which were consistent with previous studies. These findings confirmed the DOHaD hypothesis by indicating that inadequate intrauterine nutrition, here represented by HBW and VLBW, could predict later general obesity or central obesity. The study population was a well-defined, homogenous group of children and adolescents, and standardized methods were used to collect data. The effects of potential confounders such as gender, gestational age, age, stage of pubertal development, area of residence, parental BMI, parental smoking, and diet factors were taken into account. The present study had some specific limitations. First, information on birth weight was collected by self-reported interview. This form of investigation can be subject to recall bias. However, the self-reported and recorded information were highly consistent (data not shown). Second, information on birth length and growth patterns in the first year of life was not collected, so these factors were not taken into account. No adjustments were made for genetic effects. There have been studies indicating that a rapid growth rate during early years of life might also affect later obesity. For this reason, more studies, especially longitudinal studies, need to be performed.
The prenatal period is critical to the development of adiposity [36]. Overnutrition and undernutrition during pregnancy can both have permanent effects on fetal birth weight, and this may track into adulthood [37e39]. The DOHaD theory, also known as the “developmental plasticity hypothesis,” indicates that the metabolic changes that take place in individuals with LBW may be the result of fetal adaptations to inadequate intrauterine nutrition [40]. Those individuals, who have become developmentally adapted to a poor environment, may be at risk when exposed to a better one. Along this line, a series of studies have demonstrated the associations between prenatal environmental aggression and the emergence of cardiac diseases, cerebral vascular accidents, hypertension, obesity, and diabetes mellitus throughout life [14e16,41e45]. Many scientists have confirmed the existence of positive relationships between LBW and later obesity [16,17,46,47] and central obesity [24,42,48]. However, other studies have produced different results [49e52]. Strufaldi et al. and Chaudhari et al. [49,50] found LBW not to be related to the incidence of obesity. A systematic review by Yu et al. [51] involving 20 studies found LBW (<2500 g) lowered the risk of obesity (OR, 0.61; 95% CI, 0.46e0.80). Also a large-scaled meta-analysis including 643,902 individuals aged 1e75 years from 66 studies and 26 countries classified birth weight into three groups (<2500 g, 2500e4000 g, 4000 g) [52], showed a positive relationship between obesity and birth weight. Most previous studies classified the subjects with broad intervals of birth weight. These inconsistencies might be due to the effects of the different ranges of LBW used. For this reason, the present work focused on a large sample of children and adolescents, and those of LBW (<2500 g) were further subdivided into three groups as follows: <1500 g, 1500e1999 g, and 2000e2499 g. These results indicated that VLBW and mild or moderate LBW had different effects on obesity and central obesity. Children with mild and moderate LBW
Conclusions In summary, this study examined the association between birth weight and general and central obesity in childhood. J-shaped
Table 3 Associations between birth weight and the risk of obesity Birth weight, g
<1500 1500e1999 2000e2499 2500e2999 3000e3499 3500e3999 4000e4499 4500
OR (95% CI)*
General obesity Normal, n (%)
OW/OB, n (%)
39 163 440 2039 5585 3406 1147 395
8 17 68 392 1341 1013 393 134
(83.0) (90.6) (86.6) (83.9) (80.6) (77.1) (74.5) (74.7)
(17.0) (9.4) (13.4) (16.1) (19.4) (22.9) (25.5) (25.3)
1.44 (0.59e3.51) 0.35 (0.18e0.67) 0.69 (0.51e0.95) 0.83 (0.71e0.96) reference 1.14 (1.02e1.28) 1.39 (1.19e1.63) 1.36 (1.06e1.76)
P
.426 .002 .022 .015 d .020 <.001 .017
Central obesity Normal, n (%)
Central obesity, n (%)
35 145 426 2034 5658 3540 1189 402
12 35 82 394 1260 873 349 124
(74.5) (80.6) (83.9) (83.8) (81.8) (80.2) (77.3) (76.4)
(25.5) (19.4) (16.1) (16.2) (18.2) (19.8) (22.7) (23.6)
OR (95% CI)*
P
2.30 (1.03e5.14) 1.12 (0.72e1.77) 0.90 (0.67e1.20) 0.89 (0.77e1.03) reference 1.08 (0.96e1.20) 1.33 (1.13e1.56) 1.22 (0.95e1.59)
.043 .612 .473 .104 d .203 <.001 .125
* Calculated with logistic regression model adjusting for gender, gestational age, age, stage of pubertal development, area of residence, parental BMI, parental smoking status (both nonsmokers, one smoker, and both smokers), and diet factors such as food preference (meat-dominant diet, balanced diet, and vegetable-dominant diet), and salt intake (light, moderate, and high).
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relationships were observed between birth weight with BAZ and WHtR. VLBW mildly increased the risk of central obesity in childhood. These findings provide a new insight into the DOHaD theory by highlighting a potential role of VLBW in a Chinese school-aged population. Acknowledgments The authors wish to thank all the individuals who participated in the study. This study was supported by National Key Technology R&D Program of China (2012BAI02B03), Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents, and Fundamental Research Funds for the Central University. Authors’ contributions: Y-M.Z. contributed to the study design, data analysis, and wrote the article. M.Y. assisted with data analysis and assisted in writing the article. Z-P.Y. conducted the research, data analysis, and wrote the article. D-D.Z. contributed to the study design and commented on the article. L.L., J-F.F., F.X., G-L.L., C-X.G., F-H.L., S.Z., and S-K.C. contributed to the study design and data collection. References [1] Bovet P, Chiolero A, Madeleine G, Gabriel A, Stettler N. Marked increase in the prevalence of obesity in children of the Seychelles, a rapidly developing country, between 1998 and 2004. Int J Pediatr Obes 2006;1(2):120e8. [2] Jafar TH, Hatcher J, Bhutta ZA. Rapidly rising rates of overweight and obesity coupled with persistently high rates of undernutrition among school aged children in an urban Indo-Asian population: authors’ response. Arch Dis Child 2008;93(11):1000e1. [3] Mushtaq MU, Gull S, Abdullah HM, Shahid U, Shad MA, Akram J. Prevalence and socioeconomic correlates of overweight and obesity among Pakistani primary school children. BMC Public Health 2011;11:724. [4] Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 2006;1(1):11e25. [5] Balakrishnan R, Webster P, Sinclair D. Trends in overweight and obesity among 5-7-year-old White and South Asian children born between 1991 and 1999. J Public Health 2008;30(2):139e44. [6] Brambilla P, Crino A, Bedogni G, Bosio L, Cappa M, Corrias A, et al. Metabolic syndrome in children with Prader-Willi syndrome: the effect of obesity. Nutr Metab Cardiovasc Dis 2011;21(4):269e76. [7] Cali AM, Caprio S. Obesity in children and adolescents. J Clin Endocrinol Metab 2008;93(11 Suppl 1):S31e36. [8] Kohler MJ, van den Heuvel CJ. Is there a clear link between overweight/obesity and sleep disordered breathing in children? Sleep Med Rev 2008;12(5):347e61. discussion 363e344. [9] Raj M. Obesity and cardiovascular risk in children and adolescents. Indian J Endocrinol Metab 2012;16(1):13e9. [10] Barker DJ. The origins of the developmental origins theory. J Intern Med 2007;261(5):412e7. [11] Hales CN, Barker DJ. The thrifty phenotype hypothesis: type 2 diabetes. Br Med Bull 2001;60(1):5e20. [12] Oken E, Gillman MW. Fetal origins of obesity. Obes Res 2003;11(4):496e506. [13] Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986;1(8489):1077e81. [14] Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993;341(8850):938e41. [15] Curhan GC, Chertow GM, Willett WC, Spiegelman D, Colditz GA, Manson JE, et al. Birth weight and adult hypertension and obesity in women. Circulation 1996;94(6):1310e5. [16] Fall CH, Osmond C, Barker DJ, Clark PM, Hales CN, Stirling Y, et al. Fetal and infant growth and cardiovascular risk factors in women. BMJ 1995;310(6977):428e32. [17] Hua Q, Tan J, Liu ZH, Liu RK, Yang Z. A cohort study on the correlation between birth weight, simple obesity, blood lipids, blood glucose and blood pressure from childhood to adolescence. Zhonghua Nei ke Za Zhi 2007;46(11):923e5. [18] Whitaker RC, Dietz WH. Role of the prenatal environment in the development of obesity. J Pediatr 1998;132(5):768e76. [19] Curhan GC, Willett WC, Rimm EB, Spiegelman D, Ascherio AL, Stampfer MJ. Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 1996;94(12):3246e50. [20] Seidman DS, Laor A, Gale R, Stevenson DK, Danon YL. A longitudinal study of birth weight and being overweight in late adolescence. Am J Dis Child 1991;145(7):782e5. [21] Kuh D, Hardy R, Chaturvedi N, Wadsworth ME. Birth weight, childhood growth and abdominal obesity in adult life. Int J Obes Relat Metab Disord 2002;26(1):40e7.
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[22] Rolfe Ede L, Loos RJ, Druet C, Stolk RP, Ekelund U, Griffin SJ, et al. Association between birth weight and visceral fat in adults. Am J Clin Nutr 2010;92(2):347e52. [23] Malina RM, Katzmarzyk PT, Beunen G. Birth weight and its relationship to size attained and relative fat distribution at 7 to 12 years of age. Obes Res 1996;4(4):385e90. [24] Barker M, Robinson S, Osmond C, Barker DJ. Birth weight and body fat distribution in adolescent girls. Arch Dis Child 1997;77(5):381e3. [25] Hirschler V, Bugna J, Roque M, Gilligan T, Gonzalez C. Does low birth weight predict obesity/overweight and metabolic syndrome in elementary school children? Arch Med Res 2008;39(8):796e802. [26] Shi Y, De Groh M, Morrison H. Perinatal and early childhood factors for overweight and obesity in young Canadian children. Can J Public Health 2013;104(1):e69e74. [27] Garnett SP, Cowell CT, Baur LA, Fay RA, Lee J, Coakley J, et al. Abdominal fat and birth size in healthy prepubertal children. Int J Obes Relat Metab Disord 2001;25(11):1667e73. [28] Peter S, Biro L, Nemeth A, Antal M. Association between birth weight and childhood obesity in a Budapest metropolitan survey. Orv Hetil 2008;149(9):407e10. [29] Zhou D, Yang M, Yuan ZP, Zhang DD, Liang L, Wang CL, et al. Waist-to-height ratio: a simple, effective and practical screening tool for childhood obesity and metabolic syndrome. Prev Med 2014;67:35e40. [30] Must A, Anderson SE. Body mass index in children and adolescents: considerations for population-based applications. Int J Obes (Lond) 2006;30(4): 590e4. [31] World Health Organization, Department of Nutrition. WHO Growth Reference 5e19 Years. 2007 http://www.who.int/groWHtRef/en/. [32] Group of China Obesity Task Force. Body mass index reference norm for screening overweight and obesity in Chinese children and adolescents. Zhonghua Liu Xing Bing Xue Za Zhi 2004;25(2):97e102. [33] Subspecialty Group of Endocrinologic, Hereditary and Metabolic Diseases, The Society of Pediatrics, Chinese Medical Association. The definition of metabolic syndrome and prophylaxis and treatment proposal in Chinese children and adolescents. Zhonghua Er ke Za Zhi 2012;50(6):420e2. [34] Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44(235):291e303. [35] Marshall WA, Tanner JM. Variations in pattern of pubertal changes in boys. Arch Dis Child 1970;45(239):13e23. [36] Dietz WH. Critical periods in childhood for the development of obesity. Am J Clin Nutr 1994;59(5):955e9. [37] Allison DB, Paultre F, Heymsfield SB, Pi-Sunyer FX. Is the intra-uterine period really a critical period for the development of adiposity? Int J Obes Relat Metab Disord 1995;19(6):397e402. [38] Mathers JC. Early nutrition: impact on epigenetics. Forum Nutr 2007;60:42e8. [39] Martorell R, Stein AD, Schroeder DG. Early nutrition and later adiposity. J Nutr 2001;131(3):874se80s. [40] Bateson P, Barker D, Clutton-Brock T, Deb D, D’Udine B, Foley RA, et al. Developmental plasticity and human health. Nature 2004;430(6998): 419e21. [41] Murtaugh MA, Jacobs Jr DR, Moran A, Steinberger J, Sinaiko AR. Relation of birth weight to fasting insulin, insulin resistance, and body size in adolescence. Diabetes Care 2003;26(1):187e92. [42] Tian JY, Cheng Q, Song XM, Li G, Jiang GX, Gu YY, et al. Birth weight and risk of type 2 diabetes, abdominal obesity and hypertension among Chinese adults. Eur J Endocrinol 2006;155(4):601e7. [43] Barker DJ, Osmond C. Low birth weight and hypertension. BMJ 1988;297(6641):134e5. [44] Silverman BL, Rizzo TA, Cho NH, Metzger BE. Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care 1998;21(Suppl 2):B142e149. [45] Ong KK. Size at birth, postnatal growth and risk of obesity. Horm Res 2006;65(Suppl 3):65e9. [46] Oldroyd J, Renzaho A, Skouteris H. Low and high birth weight as risk factors for obesity among 4 to 5-year-old Australian children: does gender matter? Eur J Pediatr 2011;170(7):899e906. [47] Leong NM, Mignone LI, Newcomb PA, Titus-Ernstoff L, Baron JA, TrenthamDietz A, et al. Early life risk factors in cancer: the relation of birth weight to adult obesity. Int J Cancer 2003;103(6):789e91. [48] Jaiswal M, Crume T, Vehik K, Scherzinger A, Stamm E, Hamman RF, et al. Is low birth weight associated with adiposity in contemporary U.S. youth? The Exploring Perinatal Outcomes among Children (EPOCH) Study. J Dev Orig Health Dis 2012;3(3):166e72. [49] Strufaldi MW, Silva EM, Puccini RF. Overweight and obesity in prepubertal schoolchildren: the association with low birth weight and family antecedents of cardiovascular disease. Embu - metropolitan region of Sao Paulo, 2006. Cien Saude Colet 2011;16(11):4465e72. [50] Chaudhari S, Otiv M, Khairnar B, Pandit A, Hoge M, Sayyad M. Pune low birth weight study, growth from birth to adulthood. Indian Pediatr 2012;49(9):727e32. [51] Yu ZB, Han SP, Zhu GZ, Zhu C, Wang XJ, Cao XG, et al. Birth weight and subsequent risk of obesity: a systematic review and meta-analysis. Obes Rev 2011;12(7):525e42. [52] Schellong K, Schulz S, Harder T, Plagemann A. Birth weight and long-term overweight risk: systematic review and a meta-analysis including 643,902 persons from 66 studies and 26 countries globally. PLoS One 2012;7(10):e47776.
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Original article
Possible role of birth weight on general and central obesity in Chinese children and adolescents: a cross-sectional study Zhe-pin Yuan MD a,1, Min Yang MD b,1, Li Liang PhD c, Jun-Fen Fu PhD d, Feng Xiong PhD e, Ge-Li Liu PhD f, Chun-Xiu Gong MD g, Fei-Hong Luo PhD h, Shao-Ke Chen PhD i, Dan-Dan Zhang PhD j, Shuai Zhang MD j, Yi-Min Zhu PhD a, * a
Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, China Department of Nutrition and Food Safety, Zhejiang University School of Public Health, Hangzhou, China Department of Pediatrics, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China d Department of Endocrinology, Children’s Hospital of College of Medicine, Zhejiang University, Hangzhou, China e Department of Endocrinology, Children’s Hospital Affiliated to Chongqing Medical University, Chongqing, China f Department of Pediatrics, General Hospital of Tianjin Medical University, Tianjin, China g Department of Pediatrics, Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing, China h Department of Pediatric Endocrinology and Genetic Metabolic Diseases, Children’s Hospital of Fudan University, Shanghai, China i Department of Pediatrics Endocrinology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China j Department of Pathology, Zhejiang University School of Medicine, Hangzhou, China b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 4 November 2014 Accepted 8 May 2015
Purpose: According to the developmental origins of health and disease theory, fetal nutrition is associated with obesity and chronic diseases in children and adults. However, previous findings regarding the association between birth weight and childhood obesity have been inconsistent. The aim of the present study was to investigate the relationship between birth weight and childhood obesity in China. Methods: The 16,580 subjects (8477 boys and 8103 girls) aged 7e17 years, who participated in this study were recruited from a cross-sectional study in six cities in China. Epidemiological data, including birth information, were collected through face-to-face interviews, and anthropometric indices were measured by trained physicians. Overweight and obese cases were defined using sex-specific and agespecific 85th and 95th percentile body mass index (BMI) cutoffs for Han children and adolescents. Central obesity was defined using sex-specific waist-to-height ratio (WHtR) cutoffs (WHtR 0.48 in boys and WHtR 0.46 for girls). Results: The overall rate of overweight status and obesity was 20.3% in the Chinese children and adolescents and that of central obesity was 18.9%. Subjects were stratified into eight groups according to weight at birth. J-shaped relationships were observed between birth weight and BMI for age Z-score and WHtR. After adjusting for confounders such as gender, gestational age, parental factors, and dietary factors, the risk of overweight and obese status was still higher in the children with higher birth weights than in children with birth weights of 3000e3499 g (3500e3999 g: odds ratio [OR] ¼ 1.14, 95% confidence interval [CI] ¼ 1.02e1.28; 4000e4499 g: OR ¼ 1.39, 95% CI ¼ 1.19e1.63; and 4500e4999 g: OR ¼ 1.36, 95% CI ¼ 1.06e1.76). Moderately high birth weight also increased the risk of central obesity. Relative to the children with normal birth weights (3000e3499 g), the adjusted OR and 95% CI were 1.33 (1.13e1.56) in children with birth weights of 4000e4499 g. Children with very low birth weight (lower than 1500 g) had the highest risk of central obesity. The adjusted OR was 2.30 (95% CI: 1.03e5.14) relative to children with birth weights of 3000e3499 g. Conclusions: Birth weight was associated with obesity in Chinese children and adolescents. J-shaped relationships were observed between birth weight and BMI and WHtR in childhood, and very low birth weight was associated with a mild increase in the risk of central obesity in Chinese children and adolescents. Ó 2015 Elsevier Inc. All rights reserved.
Keywords: Birth weight Overweight/obesity Central obesity Childhood
The authors declare that they have no competing interest. * Corresponding author. Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, 866 Yu-hang-tang Road, Hangzhou, Zhejiang 310058, China. Tel.: þ86-571-88208138; fax: þ86-571-88208198.
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E-mail address: [email protected] (Y.-M. Zhu). These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.annepidem.2015.05.011 1047-2797/Ó 2015 Elsevier Inc. All rights reserved.
Please cite this article in press as: Yuan Zhe-pin, et al., Possible role of birth weight on general and central obesity in Chinese children and adolescents: a cross-sectional study, Annals of Epidemiology (2015), http://dx.doi.org/10.1016/j.annepidem.2015.05.011
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Background
Data collection and measurements
The prevalence of obesity in children has increased at an alarming rate in both developed and developing countries [1e4]. Childhood obesity is of particular concern because it has been widely reported to have adverse consequences on mortality and morbidity in adulthood [5e9].There has been an increasing focus that early life events might play an important role in childhood obesity [10e12]. The Developmental origins of health and disease (DOHaD) hypothesis, initially proposed by David Barker, states that poor fetal nutrition causes adaptations that increase future propensity to obesity, diabetes, and cardiovascular diseases [13,14]. Prenatal features, such as abnormal birth weight (low birth weight or high birth weight), which are used in many studies as proxies for fetal growth, might be directly associated with body mass index in childhood [12]. After this hypothesis, a number of epidemiological studies have examined the association between birth weight and later obesity. However, the results of previous works have been inconsistent. Curhan et al. [15] observed a U-shaped relationship in the Nurses’ Health Study I. This relationship was replicated in the Nurses’ Health Study II and another study on American women [16]. A study from China showed the incidences in obesity and overweight status in adolescence to be 33.3% in subjects with high birth weight and 38.9% in those with low birth weight, both significantly higher than in subjects with normal birth weight (16.2%) [17]. However, other investigators have been unable to show either high birth weight or low birth weight to be associated with an increased propensity for obesity [18e20]. Linear relationships (positive and inverse) have also been reported. For example, inverse relationships were found between birth weight and BMI, waist-hip ratio, and total abdominal fat [21e24]. However, other studies have suggested that birth weight is positively associated with BMI in later life [25e28]. For instance, Hirschler performed a study in Argentina, where she found high birth weight (HBW; birth weight 4000 g) to be associated with an increased risk of overweight status and obesity (OW/OB; odds ratio [OR] ¼ 2.48, 95% confidence interval [CI] ¼ 1.62e3.81) and metabolic syndrome (OR ¼ 3.16, 95% CI ¼ 1.38e7.24) and found low birth weight (LBW, birth weight <2500 g) to be a protective factor for OW/OB [25]. One study performed on Canadian children found that the risk of obesity increased with an OR of 1.05 (95% CI ¼ 1.00e1.09) for every 100 g of birth weight [26]. The differences in the results might be due to the different ranges of birth weight used in these studies. Owing to the limited sample sizes, previous studies did not examine the associations between different ranges of LBW with obesity. The aim of this study was to evaluate the relationship between birth weight and obesity using a relatively large-scale sample of Chinese children and adolescents.
Anthropometric measurements Anthropometric indices, including weight, height, and waist circumference (WC), were measured by well-trained investigators, after a standard protocol [29]. Height and weight were measured with the participants wearing light clothing and without shoes. WC was measured at the midpoint between the iliac crest and lowest rib. The anthropometric indices are here reported as the average of three repeated measurements. BMI was calculated as the individual’s body weight in kilograms divided by the square of his or her height in meters. Waist-to-height ratio (WHtR) was calculated as WC in centimeters divided by the height in centimeters.
Methods Subject The subjects in this study were recruited from a previous crosssectional investigation of metabolic syndrome in children and adolescents. This investigation was conducted in 2010 on the students aged 7e17 years in China and has been described in detail previously [29]. The study protocols were approved by the Research Ethics Committees at School of Public Health and Medical Ethics Committees at the Children’s Hospital of the Zhejiang University College of Medicine. All the participants and their guardians provided written informed consent.
Definitions Body mass index (BMI) was calculated as body weight divided by height squared (kg/m2), and WHtR was calculated as WC in centimeters divided by the height in centimeters. BMI was used for age Z-score (BAZ) to standardize the value of BMI across different ages and genders. Given a child’s age, gender, BMI, and an appropriate reference standard, a BMI Z-score could be calculated [30]. Here BAZs were established using BMI reference material issued by the World Health Organization 2007 (5e19 years) [31]. Overweight status was defined as body mass index (BMI) 85th percentile and <95th percentile of the BMI reference data for Han children and adolescents according to age and gender. Obesity was defined as BMI 95th percentile of the BMI reference data [32]. Central obesity was defined as WHtR is 0.48 or more in boys and WHtR is 0.46 or more in girls according to the definition of metabolic syndrome by Chinese Medical Association [33]. Subjects were divided into eight categories by birth weight: <1500 g, 1500e1999 g, 2000e2499 g, 2500e2999 g, 3000e3499 g, 3500e3999 g, 4000e4499 g, and 4500 g. Potential confounding factors Demographic variables including gender, age, gestational age, stage of pubertal development, area of residence, parental BMI, parental smoking status, food preference (meat-dominant diet, balanced diet, and vegetable-dominant diet), and salt intake (light salt, moderate salt, and heavy salt) were determined in face-to-face interviews with the participants and their parents. Stage of pubertal development was assessed using parents’ descriptions of their children’s secondary sex characteristics associated with the five standard Tanner stages [34,35]. Statistical analyses Normally distributed variables were expressed as means standard deviation and were compared using Student’s t test. Categorical variables are here expressed as frequencies (percentages); they were compared using c2 tests. Analysis of variance was used to compare BAZ and WHtR among different groups of birth weight. Binary logistic regression was used to analyze associations of birth weight with OW/OB and central obesity in childhood. All the tests were two sided, and results were considered significant at 0.05. Statistical analyses were performed using SPSS for Windows (SPSS 17.0 Inc., Chicago, IL). Results Subject characteristics Here, 16,580 subjects aged 7e17 years participated in this study. The demographic data and anthropometric variables of the subjects
Z.-p. Yuan et al. / Annals of Epidemiology xxx (2015) 1e5
stratified by gender are listed in Table 1. The boys had significantly higher levels of birth weight, weight, height, WC, BMI, BAZ, and WHtR than the girls (P < .001). The prevalence of OW/OB was 24.7% in boys, significantly higher than in girls (15.8%, P < .01). The prevalence of central obesity was 19.8% in boys, also significantly higher than in girls (18.0%, P < .01). There were no significant differences between boys and girls in gestational age at birth or area of residence (both P > .05). Relationships between birth weight with BAZ and WHtR Table 2 lists the associations of birth weight with BAZ and WHtR. There were J-shaped relationships (the highest point was at the end, and the lowest point was early in the curve) between birth weight with children’s BAZ and WHtR. Children with very low birth weight (VLBW <1500 g) had higher BAZ (0.43 1.38) than subjects in other groups, but the differences were not statistically significant (P > .05). Participants with lower birth weights (1500 g to 2999 g) had lower BAZ than those with birth weights of 3000e3499 g (average BAZ ¼ 0.21 1.10), but the difference was not statistically significant. Those with higher birth weights (3500 g) had higher BAZ, and the difference was statistically significant (P < .05). BAZ was positively related with birth weight for birth weights >1500 g (r ¼ 0.109, P < .001). The children with the highest birth weights (4500 g) had the highest BAZ (0.46 1.29). Although the children with VLBW had the highest value of WHtR (0.45 0.06) compared to other groups, the differences were also not statistically significant (P > .05). When birth weight between 3000 g and 3499 g was considered standard, higher birth weight (4000 g) was associated with higher WHtR (P < .05). Birth weight and the risk of OW/OB and central obesity The prevalence of OW/OB and central obesity in children among groups of different birth weights is shown in Table 3. J-shaped associations were found between birth weight and the prevalence of OW/OB and central obesity. The prevalence of OW/OB in children with VLBW was 17.0% (8 of 47), which was higher than in children with birth weights of 1500e1999 g, 2000e2499 g, and 2500e2999 g. The prevalence of central obesity was 25.5% (12 of 47) in children with VLBW, which was higher than in children in other groups. The prevalence of OW/OB was positively correlated with birth weight in all groups except the VLBW group. After adjusting for confounders such as gender, gestational age, age, stage of pubertal development, area of residence, parental BMI, parental smoking status, and child’s diet factors (food preferences and salt intake), higher birth weight increased the risk of childhood OW/OB compared to birth weight of 3000e3499 g (3500e3999 g: OR ¼ 1.14, 95% CI ¼ 1.02e1.28; 4000e4499 g: OR ¼ 1.39, 95% CI ¼ 1.19e1.63; 4500e4999 g: OR ¼ 1.36, 95% CI ¼ 1.06e1.76). Children with lower birth weights had a lower risk of OW/OB (1500e1999 g: OR ¼ 0.35; 95% CI ¼ 0.18e0.67; 2000e2499 g: OR ¼ 0.69, 95% CI ¼ 0.51e0.95; 2500e2999 g: OR ¼ 0.83, 95% CI ¼ 0.71e0.96). However, no statistically significant difference was found between children with VLBW and children with birth weights of 3000e3499 g with respect to risk of OW/OB. The risk of central obesity was higher in children with birth weights of 4000e4499 g (OR ¼ 1.33, 95% CI ¼ 1.13e1.56) than in children with birth weights of 3000e3499 g. Children with VLBW had the highest risk of central obesity (OR ¼ 2.03, 95% CI ¼ 1.03e5.14). A borderline association of birth weight with central obesity was found in children with birth weights of 2500e2999 g (OR ¼ 0.89, 95% CI ¼ 0.77e1.03), in children with birth weights of 3500e3999 g (OR ¼ 1.08, 95% CI ¼ 0.96e1.20), and in children with birth weights >4500 g (OR ¼ 1.22, 95% CI ¼ 0.95e1.59).
3
Table 1 Basic characteristics of the subjects* Variables
Total
Boys
n ¼ 16,580
n ¼ 8477
Age (y), n (%) 11.6 2.6 11.6 2.6 7 1010 (6.1) 543 (6.4) 8 1518 (9.2) 799 (9.4) 9 1627 (9.8) 841 (9.9) 10 1937 (11.7) 997 (11.8) 11 1760 (10.6) 924 (10.9) 12 1862 (11.2) 971 (11.5) 13 2182 (13.2) 1054 (12.4) 14 2285 (13.8) 1135 (13.4) 15 1536 (9.3) 779 (9.2) 16 682 (4.1) 334 (3.9) 17 181 (1.1) 100 (1.2) Weight (kg) 41.9 14.3 43.1 15.5 Height (cm) 147.6 15.2 148.4 16.5 WC (cm) 63.3 10.4 64.7 11.2 y BMI (kg/m ) 18.7 3.6 18.9 3.8 BAZ 0.19 1.27 0.36 1.36 WHtR 0.43 0.05 0.44 0.06 Birth weight (g) 3341.0 636.3 3403.6 645.4 Gestational 38.6 4.2 38.6 4.3 age (wk) General obesity categoryz, n (%) Normal 13214 (79.7) 6388 (75.4) Overweight 1928 (11.6) 1184 (14.0) Obese 1438 (8.7) 905 (10.7) Central obesity category,x n (%) Normal 13429 (81.1) 6782 (80.2) Central obesity 3129 (18.9) 1673 (19.8) Birth weight category (g), n (%) <1500 47 (0.3) 23 (0.3) 1500e1999 180 (1.1) 93 (1.1) 2000e2499 508 (3.1) 227 (2.7) 2500e2999 2431 (14.7) 1036 (12.2) 3000e3499 6926 (41.8) 3273 (38.6) 3500e3999 4419 (26.7) 2523 (29.8) 4000e4499 1540 (9.3) 990 (11.7) 4500 529 (3.2) 312 (3.7) Area of residence, n (%) Urban 11332 (68.3) 5798 (68.4) Rural 5248 (31.7) 2679 (31.6) Chongqing 3535 (21.3) 1757 (20.7) Hangzhou 3158 (19.0) 1773 (20.9) Nanning 2612 (15.8) 1327 (15.7) Beijing 2705 (16.3) 1407 (16.6) Shanghai 1578 (9.5) 785 (9.3) Tianjin 2992 (18.0) 1428 (16.8) Stage of pubertal developmentk, n (%) 1 5022 (31.1) 3198 (38.9) 2 3004 (18.6) 1500 (18.3) 3 2976 (18.4) 1379 (16.8) 4 2378 (14.7) 737 (9) 5 1254 (7.8) 634 (7.7)
Py
Girls n ¼ 8103 11.7 2.6 467 (5.8) 719 (8.9) 786 (9.7) 940 (11.6) 836 (10.3) 891 (11.0) 1128 (13.9) 1150 (14.2) 757 (9.3) 348 (4.3) 81 (1.0) 40.7 12.8 146.7 13.7 61.8 9.4 18.4 3.4 0.02 1.14 0.42 0.05 3275.6 620.0 38.6 4.1
.006 .054
<.001 <.001 <.001 <.001 <.001 <.001 <.001 .890 <.001
6826 (84.2) 744 (9.2) 533 (6.6) .003 6647 (82.0) 1456 (18.0) <.001 24 87 281 1395 3653 1896 550 217
(0.3) (1.1) (3.5) (17.2) (45.1) (23.4) (6.8) (2.7)
5534 2569 1778 1385 1285 1298 793 1564
(68.3) (31.7) (21.9) (17.1) (15.9) (16.0) (9.8) (19.3)
1824 1504 1597 1641 620
(23) (19) (20.2) (20.7) (7.8)
.889 <.001
<.001
* All quantitative data are expressed as mean standard deviation, all qualitative are expressed as frequency (%). y P for t tests or c2 tests. z Defined as normal (BMI for age <85th percentile); overweight (BMI for age ¼ 85the95th percentile); obesity (BMI for age 95th percentile). x Defined as central obesity (WHtR 0.48 in boys or WHtR 0.46 in girls) and normal (WHtR <0.48 in boys or WHtR <0.46 in girls). k Assessed by parents’ description of their children’s secondary sex characteristics associated with the five standard Tanner stages.
Discussion In the present study, results showed J-shaped relationships between birth weight and BMI and WHtR. Results also showed that VLBW increased the risk of central obesity in Chinese children and adolescents. These findings confirmed previous results indicating an association between HBW and obesity in later life.
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Z.-p. Yuan et al. / Annals of Epidemiology xxx (2015) 1e5
Table 2 Relationships of birth weight with BAZ and WHtR Birth weight, g
<1500 1500e1999 2000e2499 2500e2999 3000e3499 3500e3999 4000e4499 4500
N
BAZ
32 142 411 1986 5614 3618 1266 428
Py
P*
Mean
SD
Estimated marginal means
0.43 0.21 0.11 0.02 0.14 0.34 0.44 0.46
1.38 1.10 1.30 1.25 1.27 1.25 1.28 1.29
0.39 0.28 0.12 0.01 0.12 0.26 0.38 0.40
z
WHtR
SE 0.21 0.10 0.06 0.03 0.02 0.02 0.03 0.06
.998 .003 .003 .001 d <.001 <.001 <.001
d .124 .447 .830 .998 1.000 1.000 1.000
Mean
SD
Estimated marginal means
0.45 0.42 0.43 0.42 0.43 0.43 0.44 0.44
0.06 0.05 0.05 0.05 0.06 0.06 0.06 0.06
0.44 0.42 0.42 0.42 0.43 0.43 0.44 0.44
z
P*
Py
.946 .999 1.000 .776 d .592 <.001 .030
d .714 .826 .789 .946 .994 1.000 1.000
SE 0.009 0.004 0.003 0.001 0.001 0.001 0.002 0.003
SD ¼ standard deviation; SE ¼ standard error. * Based on estimated marginal means; adjustment for multiple comparisons: Sidak; reference: birth weight between 3000 g and 3499 g. y Based on estimated marginal means; adjustment for multiple comparisons: Sidak; reference: birth weight between 1500 g and 1999 g. z Adjusted for gender, gestational age, age, stage of pubertal development, area of residence, parental BMI, parental smoking status (both nonsmokers, one smoker, and both smokers), and diet factors such as food preference (meat-dominant diet, balanced diet, and vegetable-dominant diet) and salt intake (light, moderate, and high).
(1500e2999 g) had less risk of obesity and central obesity, and children with VLBW (<1500 g) had no visible difference from children of ordinary birth weight with respect to the risk of obesity, but had a higher risk of central obesity. This indicated that prior findings of a positive relationship between LBW and central obesity could be largely attributable to long-term adverse effects caused by VLBW. These findings also confirmed the positive relationships between HBW and obesity and central obesity which were consistent with previous studies. These findings confirmed the DOHaD hypothesis by indicating that inadequate intrauterine nutrition, here represented by HBW and VLBW, could predict later general obesity or central obesity. The study population was a well-defined, homogenous group of children and adolescents, and standardized methods were used to collect data. The effects of potential confounders such as gender, gestational age, age, stage of pubertal development, area of residence, parental BMI, parental smoking, and diet factors were taken into account. The present study had some specific limitations. First, information on birth weight was collected by self-reported interview. This form of investigation can be subject to recall bias. However, the self-reported and recorded information were highly consistent (data not shown). Second, information on birth length and growth patterns in the first year of life was not collected, so these factors were not taken into account. No adjustments were made for genetic effects. There have been studies indicating that a rapid growth rate during early years of life might also affect later obesity. For this reason, more studies, especially longitudinal studies, need to be performed.
The prenatal period is critical to the development of adiposity [36]. Overnutrition and undernutrition during pregnancy can both have permanent effects on fetal birth weight, and this may track into adulthood [37e39]. The DOHaD theory, also known as the “developmental plasticity hypothesis,” indicates that the metabolic changes that take place in individuals with LBW may be the result of fetal adaptations to inadequate intrauterine nutrition [40]. Those individuals, who have become developmentally adapted to a poor environment, may be at risk when exposed to a better one. Along this line, a series of studies have demonstrated the associations between prenatal environmental aggression and the emergence of cardiac diseases, cerebral vascular accidents, hypertension, obesity, and diabetes mellitus throughout life [14e16,41e45]. Many scientists have confirmed the existence of positive relationships between LBW and later obesity [16,17,46,47] and central obesity [24,42,48]. However, other studies have produced different results [49e52]. Strufaldi et al. and Chaudhari et al. [49,50] found LBW not to be related to the incidence of obesity. A systematic review by Yu et al. [51] involving 20 studies found LBW (<2500 g) lowered the risk of obesity (OR, 0.61; 95% CI, 0.46e0.80). Also a large-scaled meta-analysis including 643,902 individuals aged 1e75 years from 66 studies and 26 countries classified birth weight into three groups (<2500 g, 2500e4000 g, 4000 g) [52], showed a positive relationship between obesity and birth weight. Most previous studies classified the subjects with broad intervals of birth weight. These inconsistencies might be due to the effects of the different ranges of LBW used. For this reason, the present work focused on a large sample of children and adolescents, and those of LBW (<2500 g) were further subdivided into three groups as follows: <1500 g, 1500e1999 g, and 2000e2499 g. These results indicated that VLBW and mild or moderate LBW had different effects on obesity and central obesity. Children with mild and moderate LBW
Conclusions In summary, this study examined the association between birth weight and general and central obesity in childhood. J-shaped
Table 3 Associations between birth weight and the risk of obesity Birth weight, g
<1500 1500e1999 2000e2499 2500e2999 3000e3499 3500e3999 4000e4499 4500
OR (95% CI)*
General obesity Normal, n (%)
OW/OB, n (%)
39 163 440 2039 5585 3406 1147 395
8 17 68 392 1341 1013 393 134
(83.0) (90.6) (86.6) (83.9) (80.6) (77.1) (74.5) (74.7)
(17.0) (9.4) (13.4) (16.1) (19.4) (22.9) (25.5) (25.3)
1.44 (0.59e3.51) 0.35 (0.18e0.67) 0.69 (0.51e0.95) 0.83 (0.71e0.96) reference 1.14 (1.02e1.28) 1.39 (1.19e1.63) 1.36 (1.06e1.76)
P
.426 .002 .022 .015 d .020 <.001 .017
Central obesity Normal, n (%)
Central obesity, n (%)
35 145 426 2034 5658 3540 1189 402
12 35 82 394 1260 873 349 124
(74.5) (80.6) (83.9) (83.8) (81.8) (80.2) (77.3) (76.4)
(25.5) (19.4) (16.1) (16.2) (18.2) (19.8) (22.7) (23.6)
OR (95% CI)*
P
2.30 (1.03e5.14) 1.12 (0.72e1.77) 0.90 (0.67e1.20) 0.89 (0.77e1.03) reference 1.08 (0.96e1.20) 1.33 (1.13e1.56) 1.22 (0.95e1.59)
.043 .612 .473 .104 d .203 <.001 .125
* Calculated with logistic regression model adjusting for gender, gestational age, age, stage of pubertal development, area of residence, parental BMI, parental smoking status (both nonsmokers, one smoker, and both smokers), and diet factors such as food preference (meat-dominant diet, balanced diet, and vegetable-dominant diet), and salt intake (light, moderate, and high).
Z.-p. Yuan et al. / Annals of Epidemiology xxx (2015) 1e5
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