Abstract

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 triglycerides.

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, Triglycerides.

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.

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.

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, SD 1.01).

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 significant (P=0.03).

TABLE I 

Comparison of Mean Values at 16 Years in Low Birthweight and Normal Birthweight Groups

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 adolescents(18).

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, Chennai.

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.

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