Nutrition 30 (2014) 150158

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Nutrition
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Applied nutritional investigation

The association of birth weight with cardiovascular risk factors and mental
problems among Iranian school-aged children: The CASPIAN-III Study
Leila Azadbakht Ph.D. a, Roya Kelishadi M.D. b, *, Sahar Saraf-Bank M.Sc. a,
Mostafa Qorbani Ph.D. c, Gelayol Ardalan M.D. d, Ramin Heshmat Ph.D. e,
Mahnaz Taslimi M.Sc. f, Mohammad Esmaeil Motlagh M.D. g
a
Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
b
Pediatrics Department, Faculty of Medicine and Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
c
Department of Public Health, Alborz University of Medical Sciences, Karaj, Iran
d
Ofce of School Health, Health and Medical Education, Tehran, Iran
e
Department of Epidemiology, Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Endocrinology and Metabolism Research
Institute, Tehran University of Medical Sciences, Tehran, Iran
f
Bureau of Health and Fitness, Tehran, Iran
g
Pediatrics Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

a r t i c l e i n f o a b s t r a c t

Article history: Objective: Both high and low birth weights (HBW and LBW) are risk factors for adulthood diseases.
Received 28 December 2012 The aim of this study was to investigate the association of birth weight with cardiovascular disease
Accepted 2 June 2013 (CVD) risk factors and mental problems among Iranian school-aged children.
Methods: This national multicenter study of school-aged children entitled CASPIAN III was con-
Keywords: ducted among 5528 students in ranging from ages 10 to 18 y. Biochemical indices and anthro-
Birth weight
pometric measurements were collected. Mental health was assessed by questionnaire. To
Cardiovascular risk
investigate the association between birth weight categories and CVD risk factors and mental
Mental health
problems, multivariate logistic regression was used.
Results: HBW adolescents were at higher risk for elevated diastolic blood pressure (DBP)
(Ptrend < 0.05), low levels of high-density lipoprotein cholesterol (HDL-C) (Ptrend < 0.05), and lower
risk for general obesity (Ptrend < 0.05) compared with the LBW category. HBW had no signicant
association with mental problems (Ptrend > 0.05) compared with LBW adolescents. The results of
regression analysis, which considered normal birth weight as the reference group, showed that
LBW students had lower risk for overweight and obesity (P < 0.01), as well as higher DBP (P < 0.05)
but they were at higher risk for lower levels of HDL-C (P < 0.01). Furthermore, birth-weight cat-
egories had a U-shaped relationship with mental problems and sleep disorders (P < 0.05). Risk for
confusion was higher among the LBW group (P < 0.05).
Conclusion: Findings from this population-based study revealed a positive relation between birth
weight categories and CVD risk factors. Compared with students born with normal weight, those
born with HBW and LBW were at higher risk for mental problems, sleep disorders, and confusion.
2014 Elsevier Inc. All rights reserved.

Introduction increase the risk for cardiovascular diseases (CVDs), hyperten-

Prenatal factors have important effects on future health sta-
tus, and birth weight is an important marker of prenatal health
[1]. Fetal programming hypothesis explains that adverse uterine
environment during the critical period of fetus development, as
characterized by birth weight, may have lifelong consequences
on organ development and mental health status, and may
* Corresponding author. Tel.: 00983117923060; fax: 00983116687898.
E-mail address: kelishadi@med.mui.ac.ir (R. Kelishadi).
0899-9007/$ - see front matter 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.nut.2013.06.005
sion, and type 2 diabetes [2,3]. Several studies have implied the
relation of birth weight and the incidence of chronic diseases
later in life [4,5].
Both birth weights <2500 g and >4000 g are risk factors
for adulthood diseases [1]. It is estimated that the worldwide
prevalence of low birth weight (LBW) is 15.5%, of which 72%
are born in Asia [6]. According to a Centers for Disease Control
and Prevention (CDC) report, the percentage of infants born at
4000 to 4499 g declined from 9.1% to 7% from 1990 to 2005
[7]. It is estimated that 7.1% and 1.3% of Iranian newborn
 L. Azadbakht et al. / Nutrition 30 (2014) 150158
infants are LBW and very low birth weight (VLBW), respec-
tively [8].
A prospective cohort study reported a negative relationship
between birth weight and systolic blood pressure (SBP) among
young males [9]. One study demonstrated that children who are
born small for gestational age had higher central obesity than
large-for-gestational-age children [10]. Additionally, high birth
weight (HBW) infants have elevated risk for CVD risk factors.
A cohort study in Taiwan demonstrated a U-shaped relation
between birth weight and risk for type 2 diabetes, and a positive
relation between HBW and obesity among children ages 6 to 18 y
[11]. HBW infants had higher odds ratio (OR) for type 2 diabetes
compared with a reference group (OR, 1.78; 95% condence in-
terval [CI], 1.043.06) [12]. A cross-sectional study demonstrated
that among patients with type 1 diabetes, and those who are
born large for gestational age had higher body mass index (BMI)
and hemoglobin (Hb)A1c [13]. Moreover, a U-shaped relation
between size at birth and cardiometabolic risk was documented
in an Australian cohort [14].
Few studies have investigated the potential association be-
tween birth weight status and mental health in adulthood. Some
studies have examined the relationship between infants birth
weight and future mental health. There is no evidence regarding
the association between HBW and mental problems later in life
but recent studies have shown that LBW increases the risk for
psychiatric problems such as stress, depression, and anxiety
during the life cycle [15,16]. The results of cohort studies
demonstrated a relationship between body weight and depres-
sion and anxiety symptoms in 14-y-old adolescents [17] and
depression symptoms in young women ages 21 y [18]. Further-
more, a longitudinal study declared that LBW infants (<2.5 kg)
have higher risk for major depressive disorder (MDD) and anx-
iety disorders compared with infants weighing >3500 g at birth
[19]. Some studies demonstrated a correlation between mental
problems and development of CVD later in life [20,21]. Mental
problems such as depression or anxiety can elevate the risk for
CVD events by increasing platelet activity and aggregation, in-
ammatory cytokines, and catecholamine levels and decreasing
heart rate variability, as well as endothelial dysfunction [22].
It is noticeable that most relevant studies have been done
in developed countries [23]. However, these relationships in
developing countries are less clear. High prevalence of LBW in
developing countries compared with industrialized countries
may be one of the reasons for high prevalence of chronic diseases
in such countries [24]. The results of the rst survey of the
CASPIAN (Childhood & Adolescence Surveillance and Prevention
of Adult Non-communicable disease) study showed that girls
who are born small for gestational age and boys who had birth
weights >4000 g, are at higher risk for metabolic syndrome [25].
There is no national report with such a large sample size among
the pediatric population of the Middle East and North Africa
(MENA) on the relationship between birth weight and mental
health. To our knowledge, there is no data about the relationship
between birth weight and CVD risk factors among Iranian
school-aged children; therefore, we decided to investigate the
association between birth weight and CVD risk factors, as well as
some mental problems among this group of children.
Methods
Study design and participants
This national multicenter study of school-aged children entitled CASPIAN III
was conducted in 20092010 among 5528 urban and rural students ages 10 to
18 y, living in 27 provinces of Iran. An oral assent and an informed written
151
consent were obtained from children and their parents, respectively. The popu-
lation of study was selected by a multi-stage cluster random sampling method.
Ministry of Health and Medical Education, Ministry of Education and Training,
Child Growth and Development Research Center, Isfahan University of Medical
Sciences, and Endocrinology and Metabolism Research Institute of Tehran
University of Medical Sciences collaborated in this national survey. Detailed
methodology of this study has been reported previously [26]. Biochemical
indices (fasting blood glucose and lipid prole) were measured in this group.
Students and their parents completed a self-administered reliable and validated
questionnaire about sociodemographic status, students birth weight, behavior,
attitude, skills, and knowledge; students feeding during infancy, dietary habits of
family, as well as family history of chronic diseases (premature CVD, osteopo-
rosis, obesity, and cancers). All questionnaires, including questions on mental
health, were based on World Health Organization (WHO) Global School Health
Survey (GSHS). This study was approved by ethics committee and other relevant
national regulatory organizations.
Anthropometric measurements
Students and one of their parents were invited to school. Age and birth date
of students were registered. A team of expert nurses examined the anthropo-
metric measurements. For weight measurement, all students were barefoot and
wearing light cloths. Weight was measured nearest to 0.2 kg. Height was
measured without shoes on with accuracy of 0.2 cm. Weight and height were
measured twice and the mean of two values was reported. For BMI calculation,
weight (kg) was divided to height square (m2). Waist circumference (WC) was
measured with a non-elastic tape with accuracy of 0.2 cm. The tape was placed
between last rib and iliac crest and WC was registered after a normal expiration.
The ratio of WC to height was considered a marker of abdominal obesity, as
dened in previous studies [27,28].
Blood pressure measurement
For blood pressure measurement, we used a mercury sphygmomanometer.
SBP and diastolic blood pressure (DBP) were measured twice after more than
5 min rest, while participants were in a sitting position and calm. The average of
two time measurements was recorded and included in the analysis [29].
Biochemical assessments
For blood sampling, students and their parents were invited to the health
center nearest to their schools. Participants were asked to fast over 12 h before
doing tests. Blood samples were taken between 0800 and 0930. A healthy snack
was given to students after blood sampling. Fasting blood sugar (FBS), total
cholesterol (TC), high-density lipoprotein (HDL), and triglyceride (TG) levels were
measured. Low-density lipoprotein (LDL) was measured in samples in which TG
concentrations were <400 mg/dL.
Assessment of sociodemographic variables and birth weight
The questionnaire was prepared based on the WHO STEP-wise approved by
NCD (Tools ver. 9.5) and WHO GSHS. The questions concerning sociodemo-
graphic characteristics, and the childs birth weight were included in the parents
questionnaire, which was added to the abovementioned questionnaire [30]. The
validity and reliability of all questionnaires have been conrmed in the rst
survey of this surveillance system. Trained health care providers questioned
parents about variables related to sociodemographic issues and past history (e.g.,
maternal education, childs birth weight, family dietary habits, family history of
obesity and other chronic diseases, as well as infant duration of breastfeeding).
Parents were questioned whether their child was ever breastfed (yes/no) and
total duration of breastfeeding (in mos). We also categorized participants birth
weights to <2500 g, 2500 to 4000 g, and >4000 g.
Assessment of mental health
Students completed a comprehensive questionnaire about their socio-
demographic status, family history of diseases, sanitary habits, and general
health status. One part of general health status questionnaire of GSHS was about
mental health. Adolescents answered the mental questions including getting
angry rapidly, having anxiety, insomnia, and confusion sense. Students recorded
frequency of their mental problems according to given structure: almost every
day, more than one time per week, almost each week, almost every mo, and
seldom or never.
Statistical analysis
We categorized general characteristics of boys and girls separately by
categories of birth weight including <2500 g (term babies with birth weight
152 L. Azadbakht et al. / Nutrition 30 (2014) 150158

<2500 g), 2500 to 4000 g, and >4000 g. One-way analysis of variance (ANOVA)
with post-hoc test (Tukey test) were performed to evaluate signicant differences
in general features regarding the quantitative variables (e.g., age, BMI, WC, weight,
and height) according to birth-weight categories. We reported c2 test for signi-
cant differences of qualitative characteristics. Mean of cardiovascular risks, such as
serum lipid prole and glucose levels, as well as BP were reported by using ANOVA
(using Tukey as post hoc) with 95% condence interval across different categories
of birth weight. We used multivariable logistic regression and odds ratios (with
95% CI) to determine the association between several risk factors of CVD and birth
weight, as well as mental health. P for trend was reported to investigate dose
response correlation between birth weight and CVD risk factors, as well as mental
health. In multivariable logistic regression, we used crude model without adjust-
ment and three additionally adjusted models for several potential confounders.
The rst adjusted model was only adjusted for age and sex. The second adjusted
model was additionally adjusted for other characteristics including socioeconomic
status (SES), parents income, parents education, birth order, family history of
chronic diseases, breastfeeding duration, type of complementary food (home-
made versus commercial), and sedentary lifestyle. The third adjusted model was
additionally adjusted for BMI in all abnormalities except for overweight and
obesity. Statistical analyses were performed by using SPSS for Windows software
(version 16.0. SPSS, Chicago, IL), and values of P < 0.05 were considered statistically
signicant.
Results
The number of girls and boys included in the present study
were 2726 and 2802, respectively. The mean and SD of general
characteristics and SES of population across birth weight cate-
gories are shown in Tables 1 and 2. Boys with the birth weight
>4000 g had the highest amount of weight, WC, BMI, and height
(P < 0.05). In girls, however, a signicant relationship was found
only between BMI and birth-weight category. The boys assigned
to the birth-weight category >4000 g, had a higher prevalence of
family history of obesity, whereas this association was margin-
ally signicant in girls (P 0.06). Birth order had a signicant
correlation with birth-weight categories in this population. Ac-
cording to Table 1, 33.8% of LBW adolescents were the rst child
of family and 32.6% of HBW adolescents were fourth or more.
Regarding the parental education level and their occupation, no
signicant difference existed between the three birth weight
groups, that is, low-educated parents (<6 y), self-employed fa-
thers, and housekeeper mothers were dominant among all
birth-weight categories. The low SES (rented home and not
having car), was more frequent in the LBW girls than in their
other counterparts (P < 0.05).
A signicant relationship was observed between mental
disorders, insomnia, and confusion among boys across their
birth-weight categories. HBW boys were at higher risk for
mental disorders and insomnia. However, this relation was not
signicant among girls.

Table 1
General characteristics of participants according to birth-weight (g) categories

Boys birth weight P-value* Girls birth weight P-value*

<2500 g 25004000 g >4000 g <2500 g 25004000 g >4000 g

Age (y) 14.5  2.4 14.6  2.4 15.0  2.5 <0.05y 14.8  2.4 14.17  2.4 14.7  2.2 0.67
BMI (kg/m2) 19.1  4.0 19.6  4.1 20.1  3.8 <0.05z 18.6  3.5 19.30  4.2 19.2  3.5 <0.05#
Waist (cm) 66.0  12.3 67.5  21.5 71.0  39.1 <0.05x 69.3  32.8 69.8  17.2 69.7  10.5 0.88
Height (m) 1.49  11.3 1.51  11.7 1.53  11.5 <0.01k 1.6  15.4 1.6  15.6 1.6  16.9 0.48
Weight 43.8  12.7 45.8  13.2 47.9  12.8 <0.01{ 46.4  15.4 48.4  16.8 48.7  15.1 0.09
Breastfeeding duration (%) <0.01 <0.01
No 2.6 1.1 1.3 1.5 1.2 1
06 mo 29.7 21.7 24 31.7 20.4 20.6
612 mo 15.5 12.9 11.8 14 13.8 10.1
1218 mo 12.3 14.6 17.5 14 13.4 11.9
1824 mo 39.9 49.8 45.4 38.7 51.2 56.3
Family history of (yes %)
Diabetes 36.3 39.1 46.2 0.11 28.7 34.2 38.8 0.06
Obesity 41.8 41.1 54.2 <0.01 31.3 37.2 41.7 0.06
High blood lipids 41.1 42.7 47.8 0.36 34.4 40.8 44.5 0.06
Hypertension 50.9 51.1 59.4 0.11 43.9 48.8 46.8 0.29
Osteoporosis 17.3 18.2 21.1 0.61 13.8 15.5 20.9 0.09
Birth order (%) <0.05 <0.01
First 33.8 34.7 24.7 34.7 36.9 31.4
Second 25.1 24.9 24.3 23.7 26.6 22.2
Third 14.5 16 18.4 12.5 14.3 16.7
Fourth or more 26.6 24.4 32.6 29.1 22.2 29.7
Watching TV (%) 0.15 0.09
<2 h 34.8 28.7 29.5 31 26.4 25.2
2h 4.5 6.1 5.9 8.1 7.4 11
>2 h 60.7 65.2 64.6 60.8 66.2 63.8
Sleeping (%) 0.44 <0.05
<6 h 8.6 6.8 7.8 7.3 5.8 9.3
68 h 27 28.5 32.2 27.9 27.4 32.8
>8 h 64.4 64.7 60 64.8 66.8 57.8
Working computer (%) 0.24 0.39
<2 h 66.6 68.1 61.7 64.9 60.5 58.7
2h 18.4 16 20.4 15.5 16.3 15.4
>2 h 15 15.8 17.9 19.6 23.2 25.9

ANOVA, analysis of variance; BMI, body mass index

* P-values are resulted from ANOVA.
y
According to Tukey post hoc test, P-value between birth weight >4000 g and two other groups is P < 0.05.
z
According to Tukey post hoc test, P-value between birth weight >4000 g and birth weight <2500 is P < 0.05.
x
According to Tukey post hoc test, P-value between birth weight >4000 g and birth weight <2500 is P < 0.05.
k
According to Tukey post hoc test, P-value between birth weight <2500 g and two other groups is P < 0.05.
{
According to Tukey post hoc test, P-value between birth weight <2500 g and two other groups is P < 0.05.
#
According to Tukey post hoc test, P-value between birth weight <2500 g and birth weight 25004000 g is P < 0.05.
 L. Azadbakht et al. / Nutrition 30 (2014) 150158 153

Table 2
Socioeconomic status and mental disorders of participants according to birth-weight (g) categories

Boys birth weight P-value* Girls birth weight P-value*

<2500 g 25004000 g >4000 g <2500 g 25004000 g >4000 g

Fathers education (%) <0.01 <0.01
<6 y 54 36.9 48.7 54.2 39.1 45.3
69 y 23.9 24.6 19.5 27.1 24.9 21.7
912 y 16.6 27.4 25.4 15.7 24.8 24.7
>12 y 5.5 11.2 6.4 2.9 11.3 8.3
Mothers education (%) <0.01 <0.01
<6 y 67.3 48.6 61.2 67.2 51.3 59.3
69 y 18.7 21.9 18.8 21.2 20.6 19.2
912 y 11.3 23.7 15.8 10.1 22.3 17.9
>12 y 2.7 5.9 4.2 1.4 5.8 3.6
Fathers occupation (%) <0.01 <0.01
Employed/ofce work 16.9 24.5 21.8 17 25.4 23.2
Agriculturist 10.6 10.6 14.8 15.5 12 15.8
Workman/labor 30.3 19.6 17.9 26.9 21.5 23.6
Self-employed 34.6 39.1 41.5 30.4 35.7 30.6
Unemployed 7.6 6.3 3.9 10.2 5.3 6.7
Mothers occupation (%) 0.11 <0.01
Employed/ofce work 3 6.2 5.8 2.3 7 6.4
Agriculturist 0 0.1 0 0.9 0.3 0.3
Workwoman/labor 2 1.2 0 3.2 1 0.7
Housewife 92.8 90.7 91.7 91.9 89.9 91.3
Others 2.2 1.8 2.5 1.7 1.8 1.3
Socioeconomic status (%) 0.62 <0.01
Personal home 78.8 80.8 81.4 74.2 80.8 81.4
Rented home 21.2 19.2 18.6 25.8 19.2 18.6
Personal car (%) <0.01 <0.01
Yes 41 52.5 46.2 39.9 51.9 51.3
No 59 47.5 53.8 60.1 48.1 48.7
Number of children (%) <0.01 <0.01
<2 6.5 4.6 1.3 5.6 6.1 2
24 65.2 72.4 66.7 68 72.7 69.4
>4 28.4 23.1 32.1 26.3 21.2 28.6
Imagination of size (%) <0.05 0.06
Thin 32.1 30 35.6 25.1 24.3 19.9
Normal 23.8 20.2 13.4 24.5 23.4 18.9
Obese 44.1 49.8 51 50.4 52.3 61.1
Type of complementary feeding (%) <0.01 <0.01
Always home-made food 62.3 54.8 51.7 57.9 55.9 55.4
Always commercial foods 8.5 3.5 3.3 7.6 5.1 4.1
Usually home-made foodsa 22.2 36.3 39.2 25.4 33.5 32.4
Usually commercial foodsb 7 5.4 5.8 9.1 5.4 8.1
Mental disordersc (yes%) 74 71.1 78.2 <0.05 66.6 61.8 62.8 0.16
Angriness (yes%) 62.7 65 63.9 0.55 62.2 61.1 58.2 0.68
Anxiety (yes%) 62.1 64.9 68.8 0.23 54.2 52.4 54.4 0.71
Insomnia (yes%) 54.5 47.2 57.9 <0.01 51.1 48.1 48.6 0.62
Confusion (yes%) 40.9 35.8 41.8 0.06 40.3 34.4 35.9 0.13

* P-values are resulted from analysis of variance (ANOVA).

a
Using home-made foods, but sometimes used commercial foods.
b
Using commercial foods, but sometimes used home-made foods.
c
Including angriness, anxiety, insomnia, confusion.

Means  SDs of serum lipid proles, BP, and serum glucose
levels according to birth weight categories are shown in Table 3.
There was a signicant association between mean of HDL-C
levels across birth weight categories, which may be because of
the large sample size of the study population. Among partici-
pants with normal birth weight, the mean of HDL cholesterol
(HDL-C) levels was higher compared with other categories.
Furthermore, participants with birth weight >4000 g, had higher
means of DBP (P < 0.05). A marginal signicant difference
was observed in serum TG levels across birth-weight categories
(P 0.07).
The results of multivariate adjusted regression analyses for
cardiovascular abnormalities according to birth-weight categories
are presented in Table 4. In the conducted analyses between
general obesity and birth-weight categories, we found a marginal
correlation in crude model (Ptrend 0.06) and a negative signi-
cant association in model 2, which is adjusted for age and sex
(Ptrend < 0.05). A marginally signicant relationship between low
HDL and birth-weight categories was observed in crude model
(Ptrend 0.06). However, after adjusting for age and sex, this
positive relationship became signicant (Ptrend < 0.05). Partici-
pants who were assigned to the highest birth weight category, had
a higher risk for low HDL levels. However, in the model adjusted
for all confounding variables, we did not nd any signicant as-
sociation between birth weight and low HDL levels. Additionally, a
positive signicant association was detected between high DBP
and birth-weight categories in the crude model and the adjusted
model for age and sex (Ptrend < 0.05). After additional adjustment
for other possible confounders, this signicant association was
disappeared. Odds ratios for having other CVD risks among
different categories of birth weight were not signicant.
Table 5 shows the odds ratios (95% CI) for mental problems
according to birth-weight categories in this population. There
were no signicant trends between mental disorders, angriness,
154 L. Azadbakht et al. / Nutrition 30 (2014) 150158

Table 3
Mean of lipid proles, blood pressure, serum glucose levels, according to birth-weight (g) categories

Birth weight P-value* P-value within groupy

<2500 g 25004000 g >4000 g

HDL-C (mg/dL) 44.9  13.7a 46.6  14.4b 46.2  14.6c <0.05 ab
<0.05
ac
<0.05
LDL-C (mg/dL) 82.3  28.9 84.4  27.2 85.6  28.1 0.22
TC (mg/dL) 147.2  32.1 149.1  32.3 146.8  29.5 0.18
TG (mg/dL) 94.1  40.5 93.1  43.1 88.5  38.4 0.07
SBP (mm hg) 102.7  14.0 103.1  14.1 104.2  12.8 0.14
DBP (mm hg) 65.1  10.2a 65.7  10.9b 67.3  10.9c <0.01 ab
<0.01
bc
<0.01
FBS (mg/dL) 87.4  16.6 87.8  13.6 86.7  12.1 0.29

ANOVA, analysis of variance; DBP, diastolic blood pressure; FBS, fasting blood sugar; HDL, high density lipoprotein; LDL, low-density lipoprotein; SBP, systolic blood
pressure; TC, total cholesterol; TG, triglyceride
* P-values are resulted from ANOVA.
y
Within group P-values are resulted from Tukey post hoc test and are reported just for signicant variables in ANOVA test.
a,b,c
Mean values in a row with unlike superscripts letters are signicantly different.

anxiety, insomnia, and confusion with birth-weight categories
(Ptrend > 0.05).
The results of multivariate adjusted regression analyses for CVD
risk factors across birth-weight groups are presented in Table 6. By
considering the normal birth-weight group as reference group,
LBW adolescents had lower risk for overweight, obesity, and high
DBP in crude model and age- and sex-adjusted model (model 2)
compared with normal birth-weight category. However, after
adjusting for other confounders, this association did not remain
signicant. Furthermore, the risk for low level HDL-C cholesterol
was higher among the LBW group in crude model and model 2 that
is adjusted for age and sex. After further adjustment for other
confounding variables, this relationship was no more signicant.
Table 7 shows the results of multivariate adjusted logistic
regression for mental problems according to the birth-weight
categories. As per Table 6, the reference group is normal birth
weight participants. We documented a U-shaped relationship
between birth weight and mental disorders in models 1 and 2
(adjusted for age and sex). LBW and HBW adolescents had higher
risk for mental problems (P < 0.05). However, after adjusting
for all confounding variables, no signicant association was
documented between birth-weight categories and mental dis-
orders. Additionally, A U-shaped relation was observed between
insomnia and birth weight. After additional adjustment, this
U-shaped relation disappeared and only a negative signicant
association remained signicant between LBW and insomnia.
LBW adolescents had higher risk for insomnia according to
models 3 and 4. Additionally, a negative signicant association
was documented between LBW and confusion in the rst three
models. However, after adjusting for all confounding variables,
this relation became insignicant.
Discussion
In this large nationwide study, HBW adolescents were at
higher risk for CVD risk factors. According to our knowledge, this
is the rst study in developing countries that considers the
relationship between birth-weight status and mental health.
Although there are few reports regarding the association be-
tween birth-weight status and metabolic syndrome, we provide
the opportunity to assess the link between birth-weight status,
CVD risks, and mental health status in a large sample of Iranian
adolescents. Our results regarding increased risk for CVD in
relation to birth-weight categories and lack of association be-
tween mental disorders and birth-weight categories are similar
to previous studies [3133].
In the present study, higher birth weight was associated with
increased risk for high DBP. Limited studies conrmed our results
[13,32] and several studies showed an inverse relationship be-
tween birth weight and BP [34,35]. A longitudinal study that
followed infants from birth to 4 y, showed a U-shaped relation-
ship between birth weight and BP at 4 y. HBW infants (birth
weight 3700 g) had higher weight and BP at birth and weight
and BP had a tendency to remain high later in life [31]. A cohort
study showed that SBP in HBW infants would increase from
pre-puberty to late puberty (P < 0.05) [36]. The results of another
cohort study declared that family history of hypertension is a risk
factor for adulthood hypertension [37]. However, in our study,
HBW children had higher but non-signicant family history of
hypertension. Having high BP early in life is an important risk
factor for being hypertensive in adulthood [38].
According to previous studies, having low levels of HDL-C is
considered a CVD risk factor [39,40]. We observed a positive
relation between birth-weight categories and risk for low serum
levels of HDL-C. The results of previous studies regarding the
relationship between birth weight and serum HDL levels were
controversial. A longitudinal study that was conducted on 120
randomly selected children revealed that birth weight did not
have any effect on BMI and serum lipid measures among 6-y-old
children [41]. Another study showed that lipid proles were not
different among LBW, normal birth weight, and HBW infants
[42]. A cohort study showed no association between birth weight
and serum HDL levels among men and women aged 53 y.
However, after adjusting for current BMI and height, a positive
relation was observed among women and a positive relation was
observed among all participants after adjusting for sex [43].
Another cohort study indicated that birth weight had a positive
relation with serum TG levels and an inverse relation with serum
LDL and HDL levels among adolescents [32].
In the present study, HBW adolescents had an increased risk
for overweight and obesity, but their odds for overweight and
obesity were lower than normal birth weight adolescents. This
might be due to the cross-sectional nature of the study. It seems
that those with increased birth weight paid more attention to
their trend of weight gain. All reviewed studies demonstrated
a positive association between birth weight and BMI [44,45].
Findings from a meta-analysis ascertained that HBW resulted in
further risk for overweight/obesity in adulthood and can develop
by 0.76 kg/m2 increments in BMI compared with normal birth
weight [46].
Furthermore, we observed a marginally signicant positive
association between birth weight and central obesity. Results of
 L. Azadbakht et al. / Nutrition 30 (2014) 150158 155

Table 4 Table 5
Odds ratios (95% condence interval) for cardiovascular abnormalities according Odds ratios (95% condence interval) for mental problems according to birth-
to birth-weight (g) categories* weight (g) categories

Birth weight Ptrendy Birth weight Ptrend*

<2500 g 25004000 g >4000 g <2500 g 25004000 g >4000 g

Overweight Mental disordersy
Model Ia 1 1.5 (1.12.0) 1.4 (0.92.0) 0.13 Model Ia 1 0.8 (0.71.0) 1.0 (0.81.3) 0.80
Model IIb 1 1.5 (1.11.9) 1.4 (0.92.0) 0.07 Model IIb 1 0.8 (0.71.0) 1.0 (0.81.4) 0.99
Model IIIc 1 1.2 (0.81.8) 1.3 (0.82.1) 0.31 Model IIIc 1 0.9 (0.71.1) 1.0 (0.71.3) 0.51
Model IVd Model IVd 1 0.9 (0.71.1) 1.0 (0.71.2) 0.49
General obesity Angriness
Model I 1 1.8 (1.13.0) 1.5 (0.82.8) 0.06 Model I 1 1.0 (0.91.2) 1.0 (0.71.2) 0.60
Model II 1 1.9 (1.13.0) 1.5 (0.82.8) <0.05 Model II 1 1.0 (0.91.2) 1.0 (0.71.2) 0.58
Model III 1 1.5 (0.73.1) 2.3 (1.05.3) 0.45 Model III 1 1.3 (0.81.3) 1.0 (0.81.4) 0.80
Model IV Model IV 1 1.0 (0.81.2) 1.0 (0.71.3) 0.99
Abdominal obesity Anxiety
Model I 1 1.2 (1.01.5) 1.3 (1.01.8) 0.06 Model I 1 1.0 (0.91.2) 1.1 (0.91.4) 0.47
Model II 1 1.2 (1.01.5) 1.3 (1.01.8) 0.07 Model II 1 1.0 (0.91.2) 1.1 (0.91.4) 0.26
Model III 1 1.1 (0.81.5) 1.2 (0.81.9) 0.39 Model III 1 1.0 (0.81.2) 1.2 (0.91.6) 0.34
Model IV 1 1.1 (0.71.6) 1.0 (0.61.9) 0.93 Model IV 1 1.0 (0.81.2) 1.2 (0.91.6) 0.35
High LDL Insomnia
Model I 1 1.0 (0.71.6) 1.1 (0.62.0) 0.80 Model I 1 0.8 (0.70.9) 1.0 (0.81.2) 0.62
Model II 1 1.1 (0.71.7) 1.1 (0.62.1) 0.71 Model II 1 0.8 (0.70.9) 1.0 (0.81.2) 0.58
Model III 1 0.9 (0.51.6) 0.6 (0.21.5) 0.38 Model III 1 0.8 (0.71.0) 0.9 (0.61.2) 0.19
Model IV 1 0.9 (0.51.6) 0.6 (0.21.5) 0.37 Model IV 1 0.8 (0.71.0) 0.9 (0.61.2) 0.19
High TC Confusion
Model I 1 1.1 (0.81.6) 0.8 (0.41.4) 0.58 Model I 1 0.8 (0.70.9) 0.9 (0.71.2) 0.24
Model II 1 1.1 (0.81.6) 0.8 (0.51.5) 0.66 Model II 1 0.8 (0.70.9) 0.9 (0.71.1) 0.15
Model III 1 1.0 (0.61.6) 0.7 (0.31.4) 0.55 Model III 1 0.8 (0.61.0) 0.8 (0.61.2) 0.15
Model IV 1 1.0 (0.61.6) 0.6 (0.31.3) 0.49 Model IV 1 0.8 (0.61.0) 0.9 (0.61.2) 0.23
High TG
BMI, body mass index; SES, socioeconomic status
Model I 1 1.0 (0.71.4) 0.7 (0.41.2) 0.31
* Ptrends are resulted from logistic regression.
Model II 1 1.0 (0.71.4) 0.7 (0.41.2) 0.29 y
Including angriness, anxiety, insomnia, and confusion.
Model III 1 0.8 (0.51.2) 0.9 (0.51.7) 0.66 a
Without adjustment (crude models).
Model IV 1 0.8 (0.51.2) 0.8 (0.41.5) 0.43 b
Adjusted for age and sex.
Low HDL c
Additionally adjusted for other characteristics including SES, parents in-
Model I 1 0.8 (0.60.9) 0.8 (0.61.0) 0.06
come, parents education, birth order, family history of chronic disease, breast-
Model II 1 0.8 (0.60.9) 0.8 (0.61.0) <0.05
feeding duration, sedentary lifestyle.
Model III 1 0.8 (0.61.0) 0.8 (0.61.2) 0.19 d
Additionally adjusted for BMI in all abnormalities except for overweight and
Model IV 1 0.8 (0.61.0) 0.8 (0.61.2) 0.15
obesity.
High SBP
Model I 1 1.6 (0.92.6) 1.1 (0.62.3) 0.56
Model II 1 1.6 (0.92.6) 1.1 (0.52.1) 0.72
Model III 1 1.4 (0.82.6) 0.8 (0.32.2) 0.95 a longitudinal study revealed that HBW women had 13% more
Model IV 1 1.3 (0.72.6) 0.7 (0.32.0) 0.76
weight and 5.51 cm larger WC compared with normal birth
High DBP
Model I 1 1.9 (1.13.3) 2.3 (1.14.6) <0.05 weight women [33].
Model II 1 1.9 (1.03.3) 2.1 (1.04.2) <0.05 The odds ratio for overweight and obesity has decreased
Model III 1 2.0 (1.04.2) 1.5 (0.64.1) 0.28 across birth-weight categories, whereas the risk for central
Model IV 1 2.0 (1.04.2) 1.5 (0.54.0) 0.34 adiposity increased among the study population. This relation-
High FBS
ship showed a specic pattern of fat deposition among Iranian
Model I 1 1.0 (1.01.3) 0.9 (0.71.4) 0.84
Model II 1 1.0 (0.81.3) 0.9 (0.61.3) 0.65 adolescents [47]. Several studies have demonstrated that central
Model III 1 1.0 (0.71.3) 0.9 (0.51.3) 0.56 obesity is a major risk for CVD [48]. Central obesity is a risk factor
Model IV 1 1.0 (0.71.3) 0.8 (0.51.3) 0.55 for high DBP [49] and low serum levels of HDL-C [50]. According
ATPIII, Adult Treatment Panel III; BMI, body mass index; BP, blood pressure; CVD, to these results, we can explain the observed relationship be-
cardiovascular disease; FBS, fasting blood sugar; HDL, high-density lipoprotein; tween birth-weight categories and serum HDL levels as well as
LDL, low-density lipoprotein; SES, socioeconomic status; TC, total cholesterol; DBP among adolescents. Other CVD risk factors including high
TG, triglyceride
* Birth weight in grams, CVD abnormalities following criteria, according
levels of LDL-C, total cholesterol, TG, SBP, and fasting blood
ATPIII criteria modied for children and adolescents (overweight: BMI: 85th glucose had no signicant association with birth-weight cate-
95th; obesity: BMI >95th; low HDL: <50 mg/dL (except in boys 1519 y, that gories. These ndings are consistent with many previous studies
cutoff was <45 mg/dL); high LDL: >110 mg/dL; high TG: L00 mg/dl; high TC: [24,41].
>200 mg/dL; high FBS: >100 mg/dL; high BP: >95th adjusted by age, sex, and
According to the results of regression analysis, we did not nd
height).
y
Ptrends are resulted from logistic regression. any signicant association between birth-weight categories and
a
Without adjusted (crude models). mental disorders as well as angriness, anxiety, insomnia, and
b
Adjusted for age and sex. confusion. In this regard, ndings of previous studies were
c
Additionally adjusted for other characteristics including SES, parents in- inconsistent. Some of them failed to show any signicant relation
come, parents education, birth order, family history of chronic disease, breast-
between birth weight and mental disorders [51] and others
feeding duration, sedentary lifestyle.
d
Additionally adjusted for BMI in all abnormalities except for overweight and displayed an association between LBW and mental problems
obesity. [19]. A meta-analysis that reviewed ve cohort studies did not
156 L. Azadbakht et al. / Nutrition 30 (2014) 150158

Table 6 Table 7
Odds ratios (95% condence interval) for cardiovascular abnormalities according Odds ratios (95% condence interval) for mental problems according to birth
to birth weight categories* weight (g) categories

Birth weight Birth weight

2500 <2500 g P-valuey >4000 g P-valuez 2500 <2500 g P-value* >4000 g P-valuey
4000 g 4000 g
Overweight Mental
Model Ix 1 0.7 (0.60.9) <0.01 0.9 (0.71.1) 0.39 disordersz
Model IIk 1 0.7 (0.60.9) <0.01 0.9 (0.71.2) 0.54 Model Ix 1 1.2 (11.4) <0.05 1.2 (11.5) <0.05
Model III{ 1 0.9 (0.61.2) 0.34 1 (0.81.5) 0.73 Model IIk 1 1.2 (11.4) <0.05 1.2 (11.5) <0.05
Model IV# 1 Model III{ 1 1.1 (0.91.4) 0.39 1 (0.81.3) 0.95
General obesity Model IV# 1 1.1 (0.91.3) 0.43 1 (0.81.3) 0.95
Model I 1 0.6 (0.40.9) <0.01 0.9 (0.71.2) 0.54 Angriness
Model II 1 0.6 (0.40.8) <0.01 0.9 (0.71.3) 0.68 Model I 1 1 (0.81.1) 0.77 0.9 (0.71.1) 0.29
Model III 1 0.8 (0.61.3) 0.45 1 (0.71.6) 0.83 Model II 1 1 (0.81.1) 0.71 0.9 (0.71.1) 0.24
Model IV 1 Model III 1 1 (0.81.2) 0.78 1 (0.81.3) 0.98
Abdominal obesity Model IV 1 1 (0.81.2) 0.86 1 (0.81.2) 0.84
Model I 1 0.8 (0.61) 0.07 1.1 (0.81.4) 0.50 Anxiety
Model II 1 0.8 (0.61) 0.08 1.1 (0.81.4) 0.57 Model I 1 1 (0.81.1) 0.88 1.1 (0.91.3) 0.41
Model III 1 0.9 (0.61.2) 0.46 1.1 (0.81.5) 0.71 Model II 1 1 (0.81.1) 0.73 1.1 (11.3) 0.23
Model IV 1 0.9 (0.61.4) 0.82 1 (0.61.5) 0.89 Model III 1 1 (0.81.2) 0.98 1.2 (11.5) 0.19
High LDL Model IV 1 1 (0.81.2) 0.90 1.1 (11.4) 0.24
Model I 1 0.9 (0.61.5) 0.82 1 (0.61.7) 0.92 Insomnia
Model II 1 0.9 (0.61.5) 0.77 1 (0.61.7) 0.84 Model I 1 1.2 (11.4) <0.01 1.2 (11.5) <0.05
Model III 1 1.1 (0.61.8) 0.83 0.7 (0.31.5) 0.31 Model II 1 1.2 (11.5) <0.05 1.2 (11.5) <0.05
Model IV 1 1.1 (0.61.8) 0.83 0.7 (0.31.5) 0.31 Model III 1 1.2 (11.5) <0.05 1.1 (0.81.4) 0.56
High TC Model IV 1 1.2 (11.5) <0.05 1.1 (0.81.4) 0.61
Model I 1 0.9 (0.61.3) 0.60 0.7 (0.41.1) 0.18 Confusion
Model II 1 0.9 (0.61.3) 0.58 0.7 (0.51.1) 0.22 Model I 1 1.3 (1.11.5) <0.01 1.2 (11.4) 0.15
Model III 1 0.9 (0.61.5) 0.77 0.7 (0.41.3) 0.24 Model II 1 1.3 (1.11.5) <0.01 1.1 (0.91.4) 0.28
Model IV 1 0.9 (0.61.5) 0.79 0.7 (0.31.3) 0.21 Model III 1 1.3 (11.6) <0.05 1 (0.81.4) 0.72
High TG Model IV 1 1.2 (11.5) 0.06 1.1 (0.81.4) 0.6
Model I 1 1 (0.71.3) 0.79 0.7 (0.41) 0.09
BMI, body mass index; LBW, low birth weight; HBW, high birth weight; SES,
Model II 1 1 (0.71.3) 0.80 0.7 (0.41) 0.08
socioeconomic status
Model III 1 1.1 (0.81.7) 0.50 1 (0.61.7) 0.87
* P-values are resulted from logistic regression and compares LBW with
Model IV 1 1.2 (0.81.8) 0.38 1 (0.61.6) 0.90
normal birth weight.
Low HDL y
P-values are resulted from logistic regression and compares HBW with
Model I 1 1.3 (1.11.6) <0.01 1 (0.81.3) 0.74
normal birth weight.
Model II 1 1.3 (1.11.6) <0.01 1 (0.81.3) 0.90 z
Including angriness, anxiety, insomnia, and confusion.
Model III 1 1.2 (11.6) 0.09 1 (0.71.4) 0.91 x
Without adjustment (crude models).
Model IV 1 1.2 (11.6) 0.07 1 (0.71.4) 0.99 k
Adjusted for age and sex.
High SBP {
Additionally adjusted for other characteristics including SES, parents in-
Model I 1 0.6 (0.41) 0.08 0.7 (0.41.2) 0.25
come, parents education, birth order, family history of chronic disease, breast-
Model II 1 0.6 (0.41.1) 0.08 0.7 (0.41.2) 0.16
feeding duration, sedentary lifestyle.
Model III 1 0.7 (0.41.3) 0.27 0.6 (0.31.4) 0.26 #
Additionally adjusted for BMI in all abnormalities.
Model IV 1 0.7 (0.41.4) 0.35 0.6 (0.31.2) 0.16
High DBP
Model I 1 0.5 (0.30.9) <0.05 1.2 (0.71.9) 0.44
Model II 1 0.5 (0.31) <0.05 1.1 (0.71.8) 0.61
Model III 1 0.5 (0.21.1) 0.07 0.8 (0.41.6) 0.61 show any signicant association between birth weight and
Model IV 1 0.5 (0.21.1) 0.08 0.8 (0.41.6) 0.55 anxiety as well as depression among older people [52]. Results of
High FBS another cohort study demonstrated no substantial relation
Model I 1 1 (0.81.2) 0.85 0.9 (0.71.2) 0.62 between birth-weight percentiles and anxiety as well as opti-
Model II 1 1 (0.81.3) 0.91 1 (0.71.2) 0.46
Model III 1 1 (0.71.4) 0.90 0.9 (0.61.3) 0.50
mism [53]. Recently, several studies investigated the linkage
Model IV 1 1 (0.71.4) 0.90 0.9 (0.61.3) 0.50 between mental disorders and its effect on future incidence of
CVD [20,21]. Several studies have documented a positive relation
ATPIII, Adult Treatment Panel III; BMI, body mass index; CVD, cardiovascular
disease; DBP, diastolic blood pressure; FBS, fasting blood sugar; HDL, high- between angriness [54], insomnia [55], and anxiety [56] and
density lipoprotein; LDL, low-density lipoprotein; SBP, systolic blood pressure; risk for CVD among adults. However, in this study we observed
SES, socioeconomic status; TC, total cholesterol; TG, triglyceride no association between mental disorders and birth-weight
* Birth weight in grams; CVD abnormalities following criteria, according to ATPIII
categories.
criteria modied for children and adolescents (overweight: BMI: 85th95th; obesity:
BMI > 95th; low HDL: <50 mg/dL (except in boys ages 1519 y, that cutoff was <45
In further regression analysis in which normal birth
mg/dL); high LDL: >110 mg/dL; high TG: 100 mg/dL; high TC: >200 mg/dL; high weight was considered as reference group, we found a positive
FBS: >100 mg/dL; high blood pressure: >95th adjusted by age, sex. and height). signicant relation between LBW and overweight, obesity, and
y
P-values are resulted from logistic regression and comparing low birth high DBP. A cross-sectional study demonstrated that LBW did not
weight with normal birth weight.
z increase the risk for overweight and obesity among elementary
P-values are resulted from logistic regression and comparing high birth
weight with normal birth weight. school children [57]. A cohort study provided no data about the
x
Without adjusted (crude models). association between LBW and elevated BP among individuals
k
Adjusted for age and sex. aged 18 y [58].
{
Additionally adjusted for other characteristics including SES, parents in- In the present study, LBW students had higher risk for lower
come, parents education, birth order, family history of chronic disease, breast
feeding duration, sedentary lifestyle.
levels of HDL-C. A study conducted among Korean children re-
#
Additionally adjusted for BMI in all abnormalities except for overweight and ported lower levels of HDL-C in LBW rather than in normal birth
obesity. weight individuals [59].
 L. Azadbakht et al. / Nutrition 30 (2014) 150158
In the current study, the results of regression analysis for the
relation of birth weight and mental problems revealed a
U-shaped association between birth-weight categories and
mental disorders and insomnia. HBW and LBW adolescents were
at higher risk for mental problems and sleep disorders.
Furthermore, the risk for confusion was signicantly higher
among the LBW group. Our ndings are in line with a longitu-
dinal study that documented a U-shaped relation between birth
weight and behavioral problems. Children assigned to the rst
and last quintile of birth weight had additional risk for anxiety/
depression and social problems [17]. A retrospective study
showed a twofold increase in the risk for sleep disordered
breathing for adults born with VLBW [60].
Although previous studies provided some nutritional de-
terminants of CVD risks among Iranian adolescents [61,62], the
present study mostly focused on the birth weight as a main
determinant in a cross-sectional design.
The cross-sectional design is the main limitation of this study.
Accordingly, the other information such as catch-up growth or
weight gain during the rst year of life was not available and was
not considered in analysis. Due to the cross-sectional nature of
study, we were unable to determine causality. So, it is necessary
to perform prospective studies in this regard. Although we tried
to control the known potential confounders, we could not make
adjustments for dietary and physical activity due to inaccessi-
bility to these data. Additionally, we were unable to exclude the
effects of residual confounders. The main strength of our study
was the large sample size of adolescents that were recruited as
study participants, and multi-stage cluster random sampling
from different provinces of Iran. Using regression analysis and
adjusting for potential confounders were the other strengths of
the present study. To the best of our knowledge, it is the rst
study that investigated the relation between birth-weight cate-
gories and CVD risk factors as well as mental problem among
Iranian adolescents. Furthermore, we investigated the risk for
mental problems and CVD in HBW group compared with LBW
adolescents.
In conclusion, ndings of this population-based study revealed
a positive relation between birth-weight categories and CVD risk
factors when the LBW category was considered as the reference
group. Adolescents born with HBW had elevated risk for high
DBP, low levels of HDL-C, and central obesity. Nevertheless, ac-
cording to the results of the present study, mental problems in
the following years of life were not related to birth-weight cate-
gories. However, further analysis that considered normal birth
weight as a reference group revealed that LBW adolescents were
at lower risk for being overweight, obese, and hypertensive,
whereas the risk for low levels of HDL-C was higher among them.
Additionally, HBW and LBW students were at higher risk for
mental problems, sleep disorders, and confusion.
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