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Does antenatal micronutrient supplementation improve children’s cognitive function? Evidence from the follow-up of a double-blind randomised controlled trial in Nepal
  1. Sophiya Dulal1,
  2. Frédérique Liégeois2,
  3. David Osrin3,
  4. Adam Kuczynski4,
  5. Dharma S Manandhar1,
  6. Bhim P Shrestha1,
  7. Aman Sen1,
  8. Naomi Saville3,
  9. Delan Devakumar3,
  10. Audrey Prost3
  1. 1Mother and Infant Research Activities (MIRA), Kathmandu, Nepal
  2. 2Institute of Child Health, University College London, London, UK
  3. 3Institute for Global Health, University College London, London, UK
  4. 4Department of Clinical Neuropsychology, Great Ormond Street Children’s Hospital, London, UK
  1. Correspondence to Dr Audrey Prost; audrey.prost{at}


Introduction Multiple Micronutrient (MMN) supplementation during pregnancy can decrease the proportion of infants born low birth weight and small for gestational age. Supplementation could also enhance children’s cognitive function by improving access to key nutrients during fetal brain development and increasing birth weight, especially in areas where undernutrition is common. We tested the hypothesis that children whose mothers received MMN supplementation during pregnancy would have higher intelligence in early adolescence compared with those receiving Iron and Folic Acid (IFA) only.

Methods We followed up children in Nepal, whose mothers took part in a double-blind Randomised Controlled Trial (RCT) that compared the effects on birth weight and gestational duration of antenatal MMN versus IFA supplementation. We assessed children’s Full Scale Intelligence Quotient (FSIQ) using the Universal Non-verbal Intelligence Test (UNIT), and their executive function using the counting Stroop test. The parent trial was registered as ISRCTN88625934.

Results We identified 813 (76%) of the 1069 children whose mothers took part in the parent trial. We found no differences in FSIQ at 12 years between MMN and IFA groups (absolute difference in means (diff): 1.25, 95% CI −0.57 to 3.06). Similarly, there were no differences in mean UNIT memory (diff: 1.41, 95% CI −0.48 to 3.30), reasoning (diff: 1.17, 95% CI −0.72 to 3.06), symbolic (diff: 0.97, 95% CI −0.67 to 2.60) or non-symbolic quotients (diff: 1.39, 95% CI −0.60 to 3.38).

Conclusion Our follow-up of a double-blind RCT in Nepal found no evidence of benefit from antenatal MMN compared with IFA for children’s overall intelligence and executive function at 12 years.

  • child health
  • nutrition
  • clinical trial
  • public health

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  • Contributors The study was designed by SD and AP, with support from DD and DO. SD led the study in Nepal. FL and AK provided support with psychometric tests and checked the testers’ videos. AS designed the mobile phone questionnaire forms and databases. DSM, NS, AS and BPS provided supervision and support with staff management. SD analysed the data. SD and AP wrote the first draft. All authors were involved in data interpretation and critiqued drafts of the manuscript.

  • Funding This study was funded through a Wellcome Trust Masters Training Fellowship in Public Health and Tropical Medicine awarded to SD (101060/B/13/Z). DO is supported by the Wellcome Trust (091561/Z/10/Z). FL’s research is supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London (London, UK).

  • Disclaimer SD affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Competing interests None declared.

  • Ethics approval Our follow-up study was approved by the Nepal Health Research Council (reference 16/2015) and University College London’s research ethics committee (reference 6513/001).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.