Indian Pediatr Suppl 2009;46: S43-S47
Markers of Fetal Onset Adult Diseases: A
Comparison among Low Birthweight and Normal Birthweight
MKC Nair , Latha Nair, DS Chacko, AM Zulfikar , Babu
George and PS Sarma*
From Child Development Centre, Medical College,
Thiruvananthapuram, Kerala; and
*Department of Biostatistics, SCTIMST, Thiruvananthapuram, Kerala, India.
Correspondence to: Dr MKC Nair, Professor of Pediatrics
and Clinical Epidemiology and,
Director, Child Development Centre, Medical College, Thiruvananthapuram
695011, Kerala, India.
Objective: To observe and compare the markers of
fetal onset adult diseases among low birthweight (<2500 grams, LBW) and
normal birthweight (³2500
grams, NBW) babies at 16 years of age.
Methods: Comparative cross sectional analysis of
two groups of cohorts followed-up at 1 year and 16 years of age at Child
Development Centre (CDC), Medical College, Thiruvananthapuram. 189 LBW
babies formed the study group and 213 NBW babies formed the comparison
group. At 16 years, the parameters used for assessment of both the
groups were, body mass index (BMI) and the markers of fetal onset adult
diseases – fasting blood glucose level, fasting plasma insulin level,
total cholesterol, low density lipoprotein, high density lipoprotein and
Results: High triglyceride values and
overweight/obesity were significantly more in LBW adolescents when
compared to NBW adolescents. This has policy implications in planning
adolescent nutrition and care programs in India.
Keywords: Birthweight, India, Markers, Overweight/obesity,
he period of intrauterine growth
and development is the most vulnerable period in the human life cycle and
aberrations in this period can result in later sinister effects.
Nutritional deprivation of the fetus during critical periods of
development forces the baby to resort to adaptive survival strategies
leading to increased susceptibility to two important adult
diseases-coronary heart disease and type 2 diabetes. The Barker
hypothesis, otherwise known as the "fetal origins hypothesis", states that
cardiovascular disease and type 2 diabetes originate through the
adaptations that the fetus makes when it is undernourished(1). In relation
to insulin action and diabetes, Hales and Barker have described this
phenomenon as the "thrifty phenotype"(2-6). The basic premise of the
thrifty gene hypothesis is that certain populations may have genes that
determine increased fat storage, which in times of famine represent a
survival advantage, but in a modern environment of plenty, result in
obesity and type 2 diabetes(7,8). Thus, as a group, people who are small
at birth or during infancy remain biologically different throughout their
lives and are more likely to develop type 2 diabetes and have different
patterns of blood lipids(9-11). A correlation of hyperlipidemia with early
CAD in young individuals has been well established(12).
Substantial variation in the prevalence of diabetes in
different regions of India is well documented with very high prevalence
reported in Trivandrum(13,14). Our department has a cohort of low
birthweight (<2500grams, LBW) and normal birthweight (³2500
grams, NBW) babies, now at 16 years of age, whose accurate record of
anthropometric measurements at birth and one year are available. Hence,
this study was done with the specific objective of observing and comparing
the markers of fetal onset adult diseases among low birthweight and normal
birthweight adolescents at 16 years of age.
The study design was a comparative cross sectional
analysis of two cohorts, followed up at 1 year and 16 years of age at
Child Development Centre, Medical College, Thiruvananthapuram. The
anthropometric measurements-weight, height and head circumference of the
babies had been recorded at birth and at 1 year of age by a single
observer. At 16 years, the parameters used for assessment of both the
groups were, body mass index (BMI) and the following markers of fetal
onset adult diseases; fasting blood glucose level, fasting plasma insulin
level, total cholesterol, Low density lipoprotein (LDL), High density
lipoprotein (HDL) and triglycerides.
The study group consisted of 189 LBW adolescents and
the comparison group, 213 NBW adolescents. Sample size adequacy was
arrived at on the basis of assumptions on the expected difference in
different variables and the largest was taken. For an expected difference
in fasting blood glucose of 3.5 mg/dL between the two birthweight groups,
assuming a standard deviation of 10 mg/dL for a power of 90 % with alpha
error of 0.05, the required sample size in the two groups was 175 and
allowing for additional 25 % for loss to follow up gave 220 in each group.
With the approval of CDC human ethical committee and
after obtaining informed written consent from parents of study subjects, a
performa was used to update the baseline information for each adolescent.
Height and weight were recorded by a single observer, as per standard
procedure. Body mass index (BMI) was calculated as weight (kg) per height
For the purpose of drawing blood for fasting blood
glucose estimation, fasting blood insulin level and lipid profile, the
subjects were requested to report in a fasting state to the Advanced
Clinical Research Laboratory under quality control of Christian Medical
College, Vellore, which in turn is under constant quality control of WHO.
After the collection of blood, refreshments were provided to the
adolescents. In addition, scholastic counseling was provided to all by a
clinical psychologist. Cholesterol estimations were done by the
Cholesterol oxidase peroxidase enzymatic method. Triglyceride levels were
estimated by the Glycerol 3 phosphate oxidase peroxidase enzymatic method.
HDL levels were estimated by the Cholesterol ester hydrolase oxidase
peroxidase enzymatic method. LDL levels were calculated by the laboratory
once total cholesterol, HDL and Triglyceride estimates were available. The
homeostasis model assessment for insulin resistance (HOMA-IR) index was
calculated as fasting insulin concentration (µU/mL) X fasting glucose
concentration (mmol/L)/22.5, assuming that normal young subjects have an
insulin resistance of 1.
Student’s t test
was used to compare the means, Fishers exact test to compare the
percentages between the two groups and multiple logistic regression
analysis for multivariate analysis. Two tailed P value
was considered for statistical significance.
The outcome measurements at 16 years of age were
available for a total of 402 adolescents, 189 in the LBW (male 92, female
97) and 213 in the NBW group (male 122, female 91). The mean weight of the
LBW group at one year (7.77 Kg, SD 1.047) was significantly less (P=0.000)
than the mean weight of the normal birth weight group at one year (8.4 Kg,
Table I shows the comparison of mean
values of different parameters at 16 years between LBW and NBW groups. No
significant differences were noted in the parameters of fasting plasma
glucose, fasting plasma insulin and homeostasis model assessment for
insulin resistance (HOMA-IR) values among the low birthweight and normal
birthweight group. Also no significant difference was noted in the total
cholesterol, LDL and HDL values among the LBW and NBW groups. Table
II compares the percentage of adolescents in both groups
with abnormal values for the markers of fetal onset adult diseases. Seven
(3.7%) LBW adolescents had high levels of triglycerides (>150 mg/dL)
whereas only one (0.5%) normal birthweight adolescent had a high
triglyceride level and this difference was observed to be statistically
Comparison of Mean Values at 16 Years in Low Birthweight and Normal Birthweight Groups
Fasting glucose levels
Fasting insulin levels
Low density lipoprotein (LDL)
High density lipoprotein (HDL)
Body mass index
birthweight group; NBW: Normal birthweight group;
HOMA-IR:Homeostasis Model Assessment for Insulin Resistance
Comparison of Adolescents with Abnormal Values at 16 Years in the Two Groups
glucose (>90 mg/dL)
birthweight group, NBW: Normal birthweight group.
HOMA–IR:Homeostasis model assessment for insulin resistance,
LDL:Low density lipoprotens , HDL:High density lipoproteins,
* values in percentage of total
Adjusted Odds ratio relating Birthweight to Markers of Fetal Onset Adult Diseases: Results of
multiple logistic regression analysis
fasting plasma glucose (>90 mg/dL)
fasting plasma insulin (>24mU/mL)
total cholesterol (≥200mg/dL)
Index (>22 overweight and obese)
adjusted for sex, gestational age and bodyweight at one year
Table III gives the results of multiple
logistic regression analysis, showing the odds ratios relating birthweight
to markers of fetal onset adult diseases after adjusting for sex,
gestational age and weight at one year. High triglyceride levels were seen
more in LBW adolescents when compared to the NBW group (Odds ratio, 95% CI
0.004-0.503, P=0.01). Also overweight/obesity was significantly
more in LBW adolescents at 16 years when compared to NBW adolescents (Odds
ratio, 95% CI 0.146-0.869, P=0.02).
In view of the serious public health consequences
predicted for countries like India, with high low birthweight rates and
rapid socioeconomic transition from lack of food to plenty, the fetal
origin of adult diseases theory has to be tested in different parts of
India with geographic and ethnic variations. The availability of a cohort
of low birthweight and normal birthweight babies with reliable
anthropometric measurements at birth and one year was taken advantage of
in this study. In Kerala some marriages occur among girls at around the
school leaving age of 16 years (thus they are not available for follow up)
and hence it was thought appropriate to measure the parameters at 16 years
of age itself.
The number of low birthweight adolescents in the study
is near equal to the number of normal birthweight adolescents and also the
number of males in the study group is near equal to the number of females
making them a comparable group. The Pune children’s study observed that
lower birthweight children had higher plasma insulin and glucose
concentrations after an oral glucose load (15,16). In this study, no
significant differences were noted in the parameters of fasting plasma
glucose and fasting plasma insulin values among the low birthweight and
normal birthweight group.
A notable feature in this study was that high levels of
triglycerides (>150 mg/dL) were found in significantly higher proportion
of LBW adolescents when compared to the normal birthweight adolescents (P=0.029).
High triglyceride levels have been implicated as one of the components of
metabolic syndrome by the National Cholesterol Education Panel-III (NCEP
ATP-III) along with upper body obesity(17). A 2003 review of studies on
the relationship between birthweight and blood lipid concentrations in
later life, has reported studies with regard to triglycerides with
unadjusted analysis showing a similar negative association in
The observation that overweight/obesity and high
triglycerides are significantly more in LBW adolescents at 16 years has
policy implications for planning adolescent nutrition programs in India.
Dr Margret Leslie, ACRL, Dr L Vijayalekshmi, SAT
Hospital, Dr Suresh Kumar G, Mini KP, Asokan N, Padmamohan J, Binu T,
Vinoj Kumar, Lekshmi MA, Latha S, Maya Devi and PG-DCCD Students, Child
Development Centre, Medical College, Thiruvananthapuram.
Contributors: MKCN was involved in designing the
study and preparation of the manuscript and will act as guarantor. LN was
involved in designing the study and preparation of the manuscript, DSC was
involved in data collection and preparation of the manuscript, AMZ and BG
were involved in quality assurance of the data, and SPS was involved in
analysis of data.
Funding: Research Sub-committee, IndiaCLEN,
Competing interests: None stated. The findings and
conclusions in this article are those of the authors and do not
necessarily represent the views of the funding agency.
What this study adds?
• Low birthweight is a risk factor for
overweight/obesity and high triglyceride levels at 16 years of age.
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