Prenatal multiple micronutrient-fortified balanced energy-protein supplementation and newborn telomere length and mitochondrial DNA content: a randomized controlled efficacy trial in rural Burkina Faso

Background: Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes. The effect on markers of health and disease, such as offspring telomere length (TL) and mitochondrial DNA content (mtDNAc) is unknown. Objectives: We assessed the efficacy of maternal multiple micronutrient (MMN)-fortified balanced-energy protein (BEP) and iron-folic acid (IFA) supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome. Design: We conducted a randomized controlled trial in rural Burkina Faso, among pregnant females (15-40 years old) enrolled at <21 weeks of gestation. Mothers received either MMN-fortified BEP and IFA (intervention) or IFA only (control) throughout pregnancy. Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants, respectively. Average relative TL and mtDNAc were measured using quantitative polymerase chain reaction. Linear regression models were fitted to assess TL and mtDNAc differences across trial arms. Results: We found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn TL [β = -0.010 (95% CI: -0.057, 0.036); P = 0.662] or mtDNAc [β = 0.065 (95% CI: -0.203, 0.073); P = 0.354], as compared to an IFA tablet alone. These findings were confirmed (P >0.05) by adjusting the regression models for potential prognostic factors of study outcomes at enrollment. Exploratory analyses indicated higher, but non-significantly different mtDNAc among children born either small-for-gestational age, low birthweight, or preterm. Conclusions: Newborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03533712 ### Clinical Protocols ### Funding Statement The MIcronutriments pour la SAnte de la Mère et de le Enfant III (MISAME-III) efficacy trial was supported by the Bill & Melinda Gates Foundation (Grant number: OPP1175213). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The telomere length and mitochondrial DNA analysis was supported by the Research Foundation Flanders (Grant numbers: 12X9620N and 12X9623N) and the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program (Grant number: 946192, HUMYCO). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the ethics committee of Ghent University Hospital in Belgium (B670201734334) and the ethics committee of Institut de Recherche en Sciences de la Santé (50-2020/CEIRES). An independent Data and Safety Monitoring Board (DSMB), comprising an endocrinologist, two pediatricians, a gynecologist, and an ethicist of both Belgian and Burkinabé nationalities, was established prior to the start of the efficacy trial. The DSMB managed remote safety reviews for adverse and serious events at nine and 20 months after the start of enrolment. The MISAME-III trial was registered on ClinicalTrials.gov (identifier: [NCT03533712][1]). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03533712&atom=%2Fmedrxiv%2Fearly%2F2023%2F11%2F22%2F2023.11.22.23298825.atom