Devakumar, D; (2014) The long-term effects of antenatal multiple micronutrient supplementation in Nepal. Doctoral thesis , UCL (University College London).

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Abstract

The PhD thesis investigates the long-term effects of antenatal multiple micronutrient (MMN) supplementation. A growing body of evidence suggests that changes in early-life environment can have lasting effects on health and disease. To investigate this, we followed up children from a double-blind randomised controlled trial of MMN in pregnancy. The trial found that the intervention group were a mean 77 g heavier at birth and 204 g at 2.5 years, with a 2.5 mmHg lower mean blood pressure. The project described in the thesis set out to investigate the role of antenatal MMN intervention in the programming of future health and disease risk factors in mid-childhood. It sought to determine whether the differences in anthropometry previously present were sustained into mid-childhood and if this was due to an increase in lean mass or fat mass. It also looked at whether antenatal MMN supplementation resulted in an improvement in lung function in the children. Finally, two secondary analyses were conducted to investigate the association between socioeconomic status and growth, and air pollution and asthma. We measured anthropometry, body composition using bioelectrical impedance (with population specific isotope calibration), blood pressure, kidney dimensions by ultrasound and lung function. Data were also collected on potential confounders: socieconomic status, food security and personal air pollution exposure estimates. We assessed 841 children (422 controls, 419 intervention) at a mean age 8.5 years. Other than maternal education and residence, children lost to follow-up were no different. The unadjusted differences (intervention minus control), were 0.05 z-scores (95% CI -0.09, 0.19) for weight-for-age, 0.02 z-scores (95% CI -0.10, 0.15) for height, -0.08 z scores (95% CI - 0.19, 0.04) for forced expiratory volume in the first second, and -0.05 (95% CI -0.17, 0.06) for forced vital capacity. There was no difference in blood pressure, body circumferences, lean mass, skinfold thicknesses or kidney measurements. The adjusted differences were similar for all outcomes. When considered together, just over half the children had low weight-for-age, and approximately one-third had stunting and low body mass index. Only 1.4% of the children were overweight and mean fat mass proportion was 14.5%. When lung function was expressed in relation to predicted values for Caucasian children, FEV1 was 14% lower and FVC 12% lower. Our measures of socioeconomic status produced a multidimensional poverty index score of 0.155 and approximately one in ten households were considered food insecure in the previous year. The air pollution data showed a mean 24 hour time-weighted average of 168 μg/m3. We found an overall low prevalence of asthma, with air pollution associated with cough at night in boys only (odds ratio 1.15 per 10 μg/m3 increase in air pollution; 95% CI 1.05, 1.26). Socioeconomic status was associated with the growth of children when families owned more expensive assets and appeared to have the greatest effect on skeletal growth in early life. Differences in phenotype, body composition and lung function between children born to mothers who received antenatal MMN supplements and children whose mothers received iron and folate were not apparent at 8.5 years. While generally poor, households were comparable to those in more affluent regions of the country and were relatively food secure. The air pollution data showed that the children were exposed to levels much higher than national and international recommendations.

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