Patrick Kolsteren

Biological pathways, including individual gut microbiome are potential barriers for maternal nutritional supplementation to improvement in infant growth. We evaluated the impact of balanced energy-protein (BEP) supplementation during pregnancy and the first six months of lactation on the composition and functionality of gut microbiome in mothers and their infants in rural Burkina Faso. Our findings reveal that BEP supplementation led to a significant increase in microbiome diversity during pregnancy. In the second trimester, there was a notable decrease in the abundance of an Oscillospiraceae species, while postpartum, the abundance of Bacteroides fragilis increased. We identified concerted enriched or depleted microbial pathways associated with BEP supplementation, including the phosphotransferase system, a critical mechanism for bacterial carbohydrates uptake, which exhibited enrichment in infants born to BEP-supplemented mothers. Despite these observations, the intricate biological connections with other omics necessitate further analysis to fully elucidate the underlying comprehensive biological pathways.

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 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.

Fortified balanced energy–protein (BEP) supplementation is a promising intervention for improving maternal health, birth outcomes and infant growth in low- and middle-income countries. This nested biospecimen sub-study aimed to evaluate the physiological effect of multi-micronutrient-fortified BEP supplementation on pregnant and lactating women and their infants. Pregnant women (15–40 years) received either fortified BEP and iron–folic acid (IFA) (intervention) or IFA only (control) throughout pregnancy. The same women were concurrently randomized to receive either a fortified BEP supplement during the first 6 months postpartum in combination with IFA for the first 6 weeks (i.e., intervention) or the postnatal standard of care, which comprised IFA alone for 6 weeks postpartum (i.e., control). Biological specimens were collected at different timepoints. Multi-omics profiles will be characterized to assess the mediating effect of BEP supplementation on the different trial arms and its effect on maternal health, as well as birth and infant growth outcomes. The mediating effect of the exposome in the relationship between BEP supplementation and maternal health, birth outcomes and infant growth were characterized via biomonitoring markers of air pollution, mycotoxins and environmental contaminants. The results will provide holistic insight into the granular physiological effects of prenatal and postnatal BEP supplementation.

Aflatoxins are toxic secondary metabolites produced by Aspergillus fungi, which are ubiquitously present in the food supplies of low- and middle-income countries. Studies of maternal aflatoxin exposure and fetal outcomes are mainly focused on size at birth and the effect on intrauterine fetal growth has not been assessed. In the present study, we examine the association between chronic aflatoxin exposure during pregnancy and fetal growth trajectories in a rural setting in Ethiopia. In a prospective cohort study, we enrolled 492 pregnant females, with a singleton pregnancy and before 28 weeks of gestation. Serum aflatoxin B₁-lysine concentration was measured using liquid chromatography-tandem mass spectrometry. Three rounds of ultrasound measurements were conducted to estimate fetal weight at mean (SD) gestational age weeks of 19.1 (3.71), 28.5 (3.51), and 34.5 (2.44). Estimated fetal weight was expressed in centiles using the INTERGROWTH-21^st reference. We fitted a multivariable linear mixed-effects model to estimate the rate of fetal growth between aflatoxin-exposed (i.e., aflatoxin B₁-lysine concentration above or equal to the limit of detection) and unexposed mothers in the study. Mothers had a mean (SD) age of 26.0 (4.58) years. The median (P²⁵, P⁷⁵) serum aflatoxin B₁-lysine concentration was 12.6 (0.93, 96.9) pg/mg albumin, and aflatoxin exposure was observed in 86.6% of maternal blood samples. Eighty-five % of the females enrolled provided at least two ultrasound measurements for analysis. On average, the aflatoxin-exposed group had a significantly lower change over time in fetal weight-for-gestational age centile than the unexposed group (ß = -0.92 centiles/week, 95% CI: -1.77, -0.06, p = 0.037). Chronic maternal AF exposure is associated with lower fetal growth over time. Our findings emphasize the importance of nutrition-sensitive strategies to mitigate dietary aflatoxin exposure and adopting food safety measures in low-income settings, in particular during the fetal period of development.

Anemia and suboptimal gestational weight gain (GWG) are associated with adverse maternal and birth outcomes. Limited research indicates that balanced energy-protein (BEP) supplements reduce the incidence of inadequate GWG. We assessed the efficacy of a micronutrient-fortified BEP supplement on the secondary outcomes of anemia, GWG, GWG rate, and GWG in relation to the Institute of Medicine (IOM)’s recommendations, as compared with an iron–folic acid (IFA) tablet. We conducted a randomized controlled trial in Burkina Faso, among pregnant women (15–40 y old) enrolled at P = 0.099). Furthermore, there were no significant differences in prenatal anemia prevalence, GWG rate, GWG adequacy, or incidence of inadequate or excessive GWG. Findings were robust to model adjustments and complete case and per protocol analyses. This trial does not provide evidence that fortified BEP supplementation reduces maternal anemia or increases GWG, as compared with IFA. In conjunction with the small, but positive, effects of maternal BEP supplementation on birth outcomes, our findings warrant the investigation of additional biochemical and postnatal outcomes. This trial was registered at clinicaltrials.gov as NCT03533712.

Panel data indicate that nonpregnant women's dietary diversity fluctuates across climatic seasons in low- and middle-income countries. The natural day-to-day variability in food group consumption during gestation is unknown. A longitudinal study was conducted among pregnant women enrolled in the Micronutriments pour la Santé de la Mère et de l'Enfant study 3 randomized controlled efficacy trial [i.e., daily fortified balanced energy-protein supplement and an iron-folic acid (IFA) tablet compared with an IFA tablet only] to investigate the number of 24-hour recalls required to estimate usual prenatal food group (FG) diversity and the seasonality of pregnant women's dietary diversity in Houndé, Burkina Faso. FG consumption was assessed twice weekly by qualitative, list-based, 24-hour recalls among 1757 pregnant women (892 control, 865 intervention). The number of days needed to estimate a woman's usual prenatal 10-point FG diversity score was calculated using the within-subject coefficient of variation. Regression models, including truncated Fourier series, were fitted to assess seasonal variations in the FG diversity score and the probability of reaching Minimum Dietary Diversity for Women (MDD-W; i.e., ≥5 FGs). The monthly mean FG scores (<5 FGs) and MDD-W prevalence (<45%) were low. Five list-based recalls allowed observed FG diversity to lie within 15% of the true mean in 90% of the estimations (mean ± SD, 40.4 ± 20.7 recalls per woman). Both the FG diversity score and prevalence achieving MDD-W showed responsiveness to seasonal variations, with peaks at the end of the dry season (i.e., April or May) and troughs in the rainy season (i.e., August). Five list-based recalls are sufficient to estimate usual FG diversity during gestation, although intra-annual seasonal patterns did modestly affect the FG diversity score and MDD-W prevalence. Thus, timing of repeated dietary surveys is critical to ensure nonbiased inferences of change and trends in Burkina Faso. This trial was registered at clinicaltrials.gov as NCT 03533712.

In many low- and middle-income countries, the prevalence of energy and nutrient deficiencies is high among pregnant women. Balanced energy-protein (BEP) supplements are a promising strategy to cover nutritional requirements during pregnancy and improve birth outcomes. However, the displacement of nutrient-dense foods by BEP might attenuate the efficacy of supplementation. This cross-sectional study of participants in a randomized controlled trial evaluated the difference in energy and macro- and micronutrient intakes, food groups, and nutrient adequacy between a control and intervention group receiving either a daily iron–folic acid (IFA) tablet or IFA and BEP supplement during pregnancy, respectively. We collected a single multiple-pass 24-h recall from 470 pregnant women from the MIcronutriments pour la SAnté de la Mère et de l'Enfant (MISAME) III study that investigates the efficacy of BEP supplementation on birth outcomes and infant growth. Dietary intake (median and IQR) and nutrient adequacy were assessed using individual recipes and preparation methods of mixed dishes for each participant. Linear regression models were fitted to compare energy and nutrient intakes. Dietary energy, and macro- and micronutrient intakes were significantly higher among women in the intervention group when including BEP [2329 kcal/d (1855, 3008 kcal/d) compared with 1942 kcal/d (1575, 2405 kcal/d) in the control group (all P < 0.001)]. The difference in median energy intake (448 kcal/d; 95% CI: 291, 605 kcal/d) was approximately equivalent to a daily dose of the BEP supplement (393 kcal). Nutrient adequacy ratios for both groups were low for all micronutrients (between 0.02 and 0.66), when excluding BEP (except iron and folic acid, due to standard supplemental doses) from analysis. However, nutrient intakes increased to the Estimated Average Requirement for pregnant women when including BEP supplements. BEP supplementation increases energy and macro- and micronutrient intakes among pregnant women and fills nutrient gaps without displacing food intake. This trial was registered at clinicaltrials.gov as NCT03533712 (https://clinicaltrials.gov/ct2/show/NCT03533712).

Introduction Adequate nutrition during pregnancy is crucial to both mother and child. Maternal malnutrition can be the cause of stillbirth or lead to poor birth outcomes such as preterm delivery and small-for-gestational-age newborns. There is a probable positive effect of providing pregnant women a balanced energy-protein (BEP) food supplement, but more evidence is needed. The MIcronutriments pour la SAnté de la Mère et de l’Enfant (MISAME) III project aims to improve birth outcomes and infant growth by testing a BEP supplement during pregnancy and lactation in rural Burkina Faso. This paper describes the study protocol. Methods and analysis MISAME-III is a four-arm individually randomised efficacy trial implemented in six rural health centre catchments areas in the district of Houndé. Eligible pregnant women, aged between 15 and 40 years old and living in the study areas, will be enrolled. Women will be randomly assigned to one of the four study groups: (1) prenatal intervention only, (2) postnatal intervention only, (3) prenatal and postnatal intervention or (4) no prenatal or postnatal intervention. The intervention group will receive the BEP supplement and iron/folic acid (IFA) tablets, while the control group will only receive the IFA tablets following the national health protocol. Consumption will be supervised by trained village women on a daily basis by means of home visits. The primary outcomes are small-for-gestational age at birth and length-for-age z-score at 6 months of age. Secondary outcomes will be measured at birth and during the first 6 months of the infants’ life. Women will be enrolled from October 2019 until the total sample size is reached. Ethics and dissemination MISAME-III has been reviewed and approved by the University Hospital of Ghent and the ethics committee of Centre Muraz, Burkina Faso. Informed consent will be obtained. Results will be published in relevant journals and shared with other researchers and public health institutions. Trial registration number NCT03533712.