Lipoprotein subfraction patterns throughout gestation in The Gambia: changes in subfraction composition and their relationships with infant birth weights.

BACKGROUND: Lipoprotein subfraction concentrations have been shown to change as gestation progresses in resource-rich settings. The objective of the current study was to evaluate the impact of pregnancy on different-sized lipoprotein particle concentrations and compositions in a resource-poor setting. METHOD: Samples were collected from pregnant women in rural Gambia at enrollment (8-20 weeks), 20 weeks, and 30 weeks of gestation. Concentrations of different-sized high-density, low-density, and triglyceride-rich lipoprotein particles (HDL, LDL, and TRL, respectively) were measured by nuclear magnetic resonance in 126 pooled plasma samples from a subset of women. HDL was isolated and the HDL proteome evaluated using mass spectroscopy. Subfraction concentrations from women in The Gambia were also compared to concentrations in women in the U.S. in mid gestation. RESULTS: Total lipoprotein particles and all-sized TRL, LDL, and HDL particle concentrations increased during gestation, with the exception of medium-sized LDL and HDL particles which decreased. Subfraction concentrations were not associated with infant birth weights, though relationships were found between some lipoprotein subfraction concentrations in women with normal versus low birth weight infants (< 2500 kg). HDL's proteome also changed during gestation, showing enrichment in proteins associated with metal ion binding, hemostasis, lipid metabolism, protease inhibitors, proteolysis, and complement activation. Compared to women in the U.S., Gambian women had lower large- and small-sized LDL and HDL concentrations, but similar medium-sized LDL and HDL concentrations. CONCLUSIONS: Most lipoprotein subfraction concentrations increase throughout pregnancy in Gambian women and are lower in Gambian vs U.S. women, the exception being medium-sized LDL and HDL particle concentrations which decrease during gestation and are similar in both cohorts of women. The proteomes of HDL also change in ways to support gestation. These changes warrant further study to determine how a lack of change or different changes could impact negative pregnancy outcomes.

Environmental heat stress on maternal physiology and fetal blood flow in pregnant subsistence farmers in The Gambia, west Africa: an observational cohort study.

BACKGROUND: Anthropogenic climate change has caused extreme temperatures worldwide, with data showing that sub-Saharan Africa is especially vulnerable to these changes. In sub-Saharan Africa, women comprise 50% of the agricultural workforce, often working throughout pregnancy despite heat exposure increasing the risk of adverse birth outcomes. In this study, we aimed to improve understanding of the pathophysiological mechanisms responsible for the adverse health outcomes resulting from environmental heat stress in pregnant subsistence farmers. We also aimed to provide data to establish whether environmental heat stress also has physiological effects on the fetus. METHODS: We conducted an observational cohort study in West Kiang, The Gambia, at the field station for the Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine (named the MRC Keneba field station). Pregnant women who were aged 16 years or older and who were at <36 weeks' gestation of any gravida or parity were invited to participate in the study. Participants were eligible if they were involved in agricultural or related manual daily tasks of living. Participants were ineligible if they refused to provide consent, had multiple pregnancies (eg, if they had twins), were acutely unwell, or were diagnosed with pre-eclampsia or eclampsia. Heat stress was measured by wet bulb globe temperature (WBGT) and by using the universal thermal climate index (UTCI), and maternal heat strain was directly measured by modified physiological strain index calculated from heart rate and skin temperature. Outcome measures of fetal heart rate (FHR) and fetal strain (defined as a FHR >160 beats per min [bpm] or <115 bpm, or increase in umbilical artery resistance index) were measured at rest and during the working period. Multivariable repeated measure models (linear regression for FHR, and logistic regression for fetal strain) were used to evaluate the association of heat stress and heat strain with acute fetal strain. FINDINGS: Between Aug 26, 2019, and March 27, 2020, 92 eligible participants were recruited to the study. Extreme heat exposure was frequent, with average exposures of WBGT of 27·2°C (SD 3·6°C) and UTCI equivalent temperature of 34·0°C (SD 3·7°C). The total effect of UTCI on fetal strain resulted in an odds ratio (OR) of 1·17 (95% CI 1·09-1·29; p<0·0001), with an adjusted direct effect of OR of 1·12 (1·03-1·21; p=0·010) with each 1°C increase in UTCI. The adjusted OR of maternal heat strain on fetal strain was 1·20 (1·01-1·43; p=0·038), using the UTCI model, with each unit increase. INTERPRETATION: Data from our study show that decreasing maternal exposure to heat stress and heat strain is likely to reduce fetal strain, with the potential to reduce adverse birth outcomes. Further work that explores the association between heat stress and pregnancy outcomes in a variety of settings and populations is urgently needed to develop effective interventions. FUNDING: The Wellcome Trust.

Plasma lipids and growth faltering: A longitudinal cohort study in rural Gambian children.

Growth faltering in children arises from metabolic and endocrine dysfunction driven by complex interactions between poor diet, persistent infections, and immunopathology. Here, we determined the progression of the plasma lipidome among Gambian children (n = 409) and assessed its association with growth faltering during the first 2 years of life using the panel vector autoregression method. We further investigated temporal associations among lipid clusters. We observed that measures of stunting, wasting, and underweight are dynamically associated with each other and that lipid groups containing polyunsaturated fatty acids (PUFAs) and phosphatidylcholines consistently predict future growth outcomes. Linear growth was dynamically associated with the majority of lipids, indicating a higher nutritional demand to improve height compared to weight among growth-restricted children. Our results indicate a critical role for PUFAs and choline in early life dietary interventions to combat the child growth faltering still so prevalent in low-income settings.

Seasonal modulation of antibody response to diphtheria-tetanus-pertussis vaccination in infants: a cohort study in rural Gambia.

BACKGROUND: In rural Gambia, rates of malnutrition and infection are higher during the annual rainy/'hungry' season (June-October) in comparison to the dry/'harvest' season (November-May). The effects of this seasonal pattern on an infant's immune development and their capacity to respond to childhood vaccinations remain unclear. The aim of the current analysis was to determine whether antibody responses to diphtheria-tetanus-pertussis (DTP) vaccinations in infants differ between seasons. METHODS: Infants received the DTP vaccine at 8, 12 and 16 weeks of age and antibody titres were measured in blood samples collected at 12 (n = 710) and 24 (n = 662) weeks of age. Mean DTP antibody titres, adjusted for maternal and infant confounders, were compared by t-tests and the effect sizes of the mean differences were calculated between seasons at mid-gestation (20 weeks gestation) and first vaccination (8 weeks of infant age). RESULTS: A smaller number of infants received their first vaccination during the rainy/hungry season months compared to the dry/harvest season (n = 224 vs. n = 486). At 12 weeks, infants vaccinated during the rainy/hungry season had lower weight-for-length Z-scores (p = 0.01) and were more likely to be anaemic (p < 0.001). Their mothers, however, were pregnant mostly during the dry/harvest season, had higher weight gain (p < 0.001) and were less likely to be anaemic during pregnancy (p < 0.001). At 12 weeks, infants vaccinated during the rainy/hungry season had significantly higher mean diphtheria, tetanus and pertussis antibody titres; by 62.3, 16.9 and 19.7%, respectively (all, p < 0.001). However, at 24 weeks, they had lower mean anti-diphtheria titres (by 20.6%, p < 0.001) compared with infants vaccinated during the dry/harvest season, and no differences were observed in mean tetanus and pertussis antibody titres by vaccination season. CONCLUSIONS: Infant antibody response to the primary dose of the DTP vaccine was influenced by both season of pregnancy and infancy, although effects were diminished following three doses. Environmental exposures, including nutrition, to both the mother and infant are hypothesised as likely drivers of these seasonal effects.

Menstrual hygiene management practices and associated health outcomes among school-going adolescents in rural Gambia.

Inadequate menstrual hygiene management (MHM) practices have been associated with adverse health outcomes. This study aimed to describe MHM practices among schoolgirls from rural Gambia and assess risk factors associated with urogenital infections and depressive symptoms. A cross-sectional study was conducted among adolescent schoolgirls in thirteen schools in rural Gambia. A questionnaire was used to collect information on socio-demographics, MHM practices and clinical symptoms of reproductive and urinary tract infections (UTIs). A modified Beck Depression Inventory-II was used to screen for depressive symptoms. Mid-stream urine samples were collected to assess for UTIs. Modified Poisson regression analysis was used to determine risk factors for symptoms of urogenital infections and depression among adolescent girls. Three hundred and fifty-eight girls were recruited. Although, 63% of the girls attended schools providing free disposable pads, reusable cloths/towels were the commonest absorbent materials used. Heavy menstrual bleeding was associated with depressive symptoms (adjusted prevalence ratio, aPR 1.4 [95% CI 1.0, 1.9]), while extreme menstrual pain (aPR 1.3 [95% CI 1.2, 1,4]), accessing sanitary pads in school (aPR 1.4 [95% CI 1.2, 1.5]) and less access to functional water source at school (aPR 1.4 [95% CI 1.3, 1.6]) were associated with UTI symptoms. Conversely, privacy in school toilets (aPR 0.6 [95% CI 0.5, 0.7]) was protective for UTI symptoms. Heavy menstrual bleeding (aPR 1.4 [95% CI 1.1, 2.0]) and taking <30 minutes to collect water at home were associated with RTI symptoms (aPR 1.2 [95% CI 1.0, 1.5]) while availability of soap in school toilets (aPR 0.6 [95% CI 0.5, 0.8] was protective for RTI symptoms. Interventions to ensure that schoolgirls have access to private sanitation facilities with water and soap both at school and at home could reduce UTI and RTI symptoms. More attention is also needed to support girls with heavy menstrual bleeding and pain symptoms.

A Novel method for the identification and quantification of weight faltering.

OBJECTIVE: We describe a new method for identifying and quantifying the magnitude and rate of short-term weight faltering episodes, and assess how (a) these episodes relate to broader growth outcomes, and (b) different data collection intervals influence the quantification of weight faltering. MATERIALS AND METHODS: We apply this method to longitudinal growth data collected every other day across the first year of life in Gambian infants (n = 124, males = 65, females = 59). Weight faltering episodes are identified from velocity peaks and troughs. Rate of weight loss and regain, maximum weight loss, and duration of each episode were calculated. We systematically reduced our dataset to mimic various potential measurement intervals, to assess how these intervals affect the ability to derive information about short-term weight faltering episodes. We fit linear models to test whether metrics associated with growth faltering were associated with growth outcomes at 1 year, and generalized additive mixed models to determine whether different collection intervals influence episode identification and metrics. RESULTS: Three hundred weight faltering episodes from 119 individuals were identified. The number and magnitude of episodes negatively impacted growth outcomes at 1 year. As data collection interval increases, weight faltering episodes are missed and the duration of episodes is overestimated, resulting in the rate of weight loss and regain being underestimated. CONCLUSIONS: This method identifies and quantifies short-term weight faltering episodes, that are in turn negatively associated with growth outcomes. This approach offers a tool for investigators interested in understanding how short-term weight faltering relates to longer-term outcomes.

Timing of the Infancy-Childhood Growth Transition in Rural Gambia.

The Karlberg model of human growth describes the infancy, childhood, and puberty (ICP) stages as continuous and overlapping, and defined by transitions driven by sequential additional effects of several endocrine factors that shape the growth trajectory and resultant adult size. Previous research has suggested that a delayed transition from the infancy to the childhood growth stage contributes to sub-optimal growth outcomes. A new method developed to analyze the structure of centile crossing in early life has emerged as a potential tool for identifying the infancy-childhood transition (ICT), through quantifying patterns of adjacent monthly weight-for-age z-score (WAZ) deviation correlations. Using this method, the infancy-childhood transition was identified as taking place at around 12 months of age in two cohorts of UK infants. Here, we apply this method to data collected as part of a longitudinal growth study in rural Gambia [the Hormonal and Epigenetic Regulators of Growth, or HERO-G study, N = 212 (F = 99, M = 113)], in order to identify the ICT and assess whether timing of this transition differs across groups based on sex or birth seasonality. We calculated Pearson correlation coefficients for adjacent monthly WAZ score deviations. Based on the patterns of change in the correlation structure over time, our results suggest that the infancy-childhood transition occurs at around 9 months of age in rural Gambian infants. This points to an accelerated ICT compared to UK infants, rather than a delayed ICT. A comparatively later transition, seen in UK infants, allows maximal extension of the high rates of growth during the infancy stage; an earlier transition as seen in Gambian infants cuts short this period of rapid growth, potentially impacting on growth outcomes in childhood while diverting energy into other processes critical to responses to acute infectious challenges. Growth in later developmental stages in this population offers an extended window for catch-up.

Maternal plasma lipid levels across pregnancy and the risks of small-for-gestational age and low birth weight: a cohort study from rural Gambia.

BACKGROUND: Sub-optimal maternal lipid levels during pregnancy may be implicated in the pathophysiological mechanisms leading to low birth weight (LBW) and small-for-gestational-age (SGA). We aimed to determine whether maternal lipid levels across pregnancy were associated with birth weight and the risks of LBW and SGA in rural Gambia. METHODS: This secondary analysis of the ENID trial involved 573 pregnant women with term deliveries. Plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were analyzed at enrolment (mean (SD) = 13.9 (3.3) weeks gestation), 20 and 30 weeks gestation as continuous variables and percentile groups. Regression models with adjustment for confounders were used to examine associations between gestational lipid levels and birth weight and the risks of LBW (birth weight < 2500 g) and SGA (<10th percentile INTERGROWTH-21ST for birth weight). RESULTS: There were 7.9% LBW and 32.5% SGA infants. At enrolment, every unit increase in HDL-c was associated with a 2.7% (P = 0.011) reduction in relative risk of LBW. At 20 weeks gestation, every unit increase in TC levels was associated with a 1.3% reduction in relative risk of LBW (P = 0.002). Low (<10th percentile) HDL-c at enrolment or at 20 weeks gestation was associated with a 2.6 (P = 0.007) and 3.0 (P = 0.003) times greater risk of LBW, respectively, compared with referent (10th─90th) HDL-c. High (>90th percentile) LDL-c at 30 weeks gestation was associated with a 55% lower risk of SGA compared with referent LDL-c (P = 0.017). Increased levels of TC (ß = 1.3, P = 0.027) at 20 weeks gestation and of TC (ß = 1.2, P = 0.006) and LDL-c (ß = 1.5, P = 0.002) at 30 weeks gestation were all associated with higher birth weight. CONCLUSIONS: In rural Gambia, lipid levels during pregnancy were associated with infant birth weight and the risks of LBW and SGA. Associations varied by lipid class and changed across pregnancy, indicating an adaptive process by which maternal lipids may influence fetal growth and birth outcomes. TRIAL REGISTRATION: This trial was registered as ISRCTN49285450 on: 12/11/2009.

Impact of nutritional supplementation during pregnancy on antibody responses to diphtheria-tetanus-pertussis vaccination in infants: A randomised trial in The Gambia.

BACKGROUND: Exposure to a nutritionally deficient environment during fetal life and early infancy may adversely alter the ontogeny of the immune system and affect an infant's ability to mount an optimal immune response to vaccination. We examined the effects of maternal nutritional supplementation during pregnancy on infants' antibody responses to the diphtheria-tetanus-pertussis (DTP) vaccine included in the Expanded Programme on Immunisation (EPI). METHODS AND FINDINGS: The Early Nutrition and Immune Development (ENID) trial was a randomised, partially blinded trial conducted between April 2010 and February 2015 in the rural West Kiang region of The Gambia, a resource-poor region affected by chronic undernutrition. Pregnant women (<20 weeks' gestation) with a singleton pregnancy (n = 875) were randomised to receive one of four supplements: iron-folic acid (FeFol; standard of care), multiple micronutrient (MMN), protein-energy (PE), or PE + MMN daily from enrolment (mean [SD] 13.7 [3.3] weeks' gestation) until delivery. Infants were administered the DTP vaccine at 8, 12, and 16 weeks of age according to the Gambian Government protocol. Results for the primary outcome of the trial (infant thymic size) were described previously; here, we report on a secondary outcome, infant antibody response to vaccination. The effects of supplementation on mean DTP antibody titres measured in blood samples collected from infants at 12 weeks (n = 710) and 24 weeks (n = 662) were analysed with adjustment for confounders including maternal age, compliance to supplement, and infant sex and season. At 12 weeks, following a single dose of the vaccine, compared with FeFol (mean 95% confidence interval [CI]; 0.11 IU/mL, 0.09-0.12), antenatal supplementation with MMN or MMN + PE resulted in 42.4% (95% CI 20.1-64.6; p < 0.001) and 29.4% (6.4-52.5; p = 0.012) higher mean anti-diphtheria titres, respectively. Mean anti-tetanus titres were higher by 9.0% (5.5-12.5), 7.8% (4.3-11.4), and 7.3% (4.0-10.7) in MMN, PE, and PE + MMN groups (all, p < 0.001), respectively, than in the FeFol group (0.55 IU/mL, 0.52-0.58). Mean anti-pertussis titres were not significantly different in the FeFol, MMN, and PE + MNN groups but were all higher than in the PE group (all, p < 0.001). At 24 weeks, following all three doses, no significant differences in mean anti-diphtheria titres were detected across the supplement groups. Mean anti-tetanus titres were 3.4% (0.19-6.5; p = 0.038) higher in the PE + MMN group than in the FeFol group (3.47 IU/mL, 3.29-3.66). Mean anti-pertussis titres were higher by 9.4% (3.3-15.5; p = 0.004) and 15.4% (9.6-21.2; p < 0.001) in PE and PE + MMN groups, compared with the FeFol group (74.9 IU/mL, 67.8-82.8). Limitations of the study included the lack of maternal antibody status (breast milk or plasma) or prevaccination antibody measurements in the infants. CONCLUSION: According to our results from rural Gambia, maternal supplementation with MMN combined with PE during pregnancy enhanced antibody responses to the DTP vaccine in early infancy. Provision of nutritional supplements to pregnant women in food insecure settings may improve infant immune development and responses to EPI vaccines. TRIAL REGISTRATION: ISRCTN49285450.

A rite of passage: a mixed methodology study about knowledge, perceptions and practices of menstrual hygiene management in rural Gambia.

BACKGROUND: Appropriate menstrual hygiene management (MHM) is impeded by taboos and secrecy surrounding menstruation. Unhygienic menstrual practices and unpreparedness for managing menstruation has been associated with adverse health and social outcomes among adolescent girls. In The Gambia, there is limited data on menstrual practices among girls and women in rural communities and the sources of information about menstruation for the adolescents. This study aimed to explore knowledge, preparedness and practices of menstruation and its management among adolescents, mothers and teachers in rural Gambia. METHODS: A mixed methods study was conducted in the rural Kiang West district of The Gambia. Twenty focus group discussions and thirteen in-depth interviews were conducted among mothers, adolescents and teachers to explore their views on menstruation, cultural beliefs, sources and level of knowledge on menstruation and MHM practices. In addition, a survey was done among 331 school girls to assess their knowledge, practices and attitudes of menstruation and its management. Inductive content analysis was used to analyse the qualitative data, and descriptive analysis and chi-squared tests were used to analyse quantitative data. RESULTS: All participants had different levels of knowledge about menstruation. Knowledge score was higher among post-menarche girls compare with pre-menarche girls (p = 0.0001). All groups expressed difficulties, embarrassment and shame in relation to discussing menstruation. Two thirds of the surveyed girls reported having learnt about menstruation before menarche, however at menarche most felt unprepared. Teachers were the main source of information, but when asking for advice most girls preferred to ask their mothers. Mothers reported facing difficulties in discussing menstruation with their children and felt that boys did not need to be taught about it, however boys were very curious to know about. Most girls used reusable cloth unless they are given free pads from school. CONCLUSION: Taboos, secrecy and embarrassment associated with discussing menstruation hinder adolescents from seeking advice from parents and teachers on appropriate MHM practices. Strategies to encourage positive social norms towards menstruation would help to promote more open discussions about it at the family, community and national level, which will support improvements in MHM in this and similar communities in low and middle income settings.

Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial.

BACKGROUND: Thymic size in early infancy predicts subsequent survival in low-income settings. The human thymus develops from early gestation, is most active in early life and is highly sensitive to malnutrition. Our objective was to test whether thymic size in infancy could be increased by maternal and/or infant nutritional supplementation. METHODS: The Early Nutrition and Immune Development (ENID) Trial was a randomized 2 × 2 × 2 factorial, partially blinded trial of nutritional supplementation conducted in rural Gambia, West Africa. Pregnant women (N = 875) were randomized to four intervention groups (iron-folate (standard care), multiple micronutrients, protein energy or protein energy + multiple micronutrients at 'booking' (mean gestational age at enrolment = 13.6 weeks, range 8-20 weeks) until delivery. The iron-folate and multiple micronutrient arms were administered in tablet form and the protein energy arms as a lipid-based nutritional supplement. All intervention arms contained 60 mg iron and 400 µg folic acid per daily dose. From 24 to 52 weeks of age, infants from all groups were randomized to receive a daily lipid-based nutritional supplement, with or without additional micronutrients. Thymic size was assessed by ultrasonography at 1, 8, 24 and 52 weeks of infant age, and a volume-related thymic index calculated. Detailed data on infant growth, feeding status and morbidity were collected. RESULTS: A total of 724 (82.7%) mother-infant pairs completed the trial to infant age 52 weeks. Thymic size in infancy was not significantly associated with maternal supplement group at any post-natal time point. Infants who received the daily LNS with additional micronutrients had a significantly larger thymic index at 52 weeks of age (equivalent to an 8.0% increase in thymic index [95% CI 2.89, 13.4], P = 0.002). No interaction was observed between maternal and infant supplement groups. CONCLUSIONS: A micronutrient-fortified lipid-based supplement given in the latter half of infancy increased thymic size, a key mediator of immune function. Improving the micronutrient status of infants from populations with marginal micronutrient status may improve immune development and survival. TRIAL REGISTRATION: ISRCTN registry (controlled-trials.com) Identifier: ISRCTN49285450.

Preconceptional and gestational weight trajectories and risk of delivering a small-for-gestational-age baby in rural Gambia.

Background: Maternal nutritional status is a key determinant of small for gestational age (SGA), but some knowledge gaps remain, particularly regarding the role of the energy balance entering pregnancy.Objective: We investigated how preconceptional and gestational weight trajectories (summarized by individual-level traits) are associated with SGA risk in rural Gambia.Design: The sample comprised 670 women in a trial with serial weight data (7310 observations) that were available before and during pregnancy. Individual trajectories from 6 mo before conception to 30 wk of gestation were produced with the use of multilevel modeling. Summary traits were expressed as weight z scores [weight z score at 3 mo preconception (zwt-3 mo), weight z score at conception, weight z score at 3 mo postconception, weight z score at 7 mo postconception (zwt+7 mo), and conditional measures that represented the change from the preceding time] and were related to SGA risk with the use of Poisson regression with confounder adjustment; linear splines were used to account for nonlinearity.Results: Maternal weight at each time point had a consistent nonlinear relation with SGA risk. For example, the zwt-3 mo estimate was stronger in women with values ≤0.5 (RR: 0.736; 95% CI: 0.594, 0.910) than in women with values >0.5 (RR: 0.920; 95% CI: 0.682, 1.241). The former group had the highest observed SGA prevalence. Focusing on weight change, only conditional zwt+7 mo was associated with SGA and only in women with values >-0.5 (RR: 0.579; 95% CI: 0.463, 0.724).Conclusions: Protection against delivering an SGA neonate offered by greater preconceptional or gestational weight may be most pronounced in more undernourished and vulnerable women. Independent of this possibility, greater second- and third-trimester weight gain beyond a threshold may be protective. This trial was registered at http://www.isrctn.com/ as ISRCTN49285450.

Association of prenatal lipid-based nutritional supplementation with fetal growth in rural Gambia.

Prenatal supplementation with protein-energy (PE) and/or multiple-micronutrients (MMNs) may improve fetal growth, but trials of lipid-based nutritional supplements (LNSs) have reported inconsistent results. We conducted a post-hoc analysis of non-primary outcomes in a trial in Gambia, with the aim to test the associations of LNS with fetal growth and explore how efficacy varies depending on nutritional status. The sample comprised 620 pregnant women in an individually randomized, partially blinded trial with four arms: (a) iron and folic acid (FeFol) tablet (usual care, referent group), (b) MMN tablet, (c) PE LNS, and (d) PE + MMN LNS. Analysis of variance examined unadjusted differences in fetal biometry z-scores at 20 and 30 weeks and neonatal anthropometry z-scores, while regression tested for modification of intervention-outcome associations by season and maternal height, body mass index, and weight gain. Despite evidence of between-arm differences in some fetal biometry, z-scores at birth were not greater in the intervention arms than the FeFol arm (e.g., birth weight z-scores: FeFol -0.71, MMN -0.63, PE -0.64, PE + MMN -0.62; group-wise p = .796). In regression analyses, intervention associations with birth weight and head circumference were modified by maternal weight gain between booking and 30 weeks gestation (e.g., PE + MMN associations with birth weight were +0.462 z-scores (95% CI [0.097, 0.826]) in the highest quartile of weight gain but -0.099 z-scores (-0.459, 0.260) in the lowest). In conclusion, we found no strong evidence that a prenatal LNS intervention was associated with better fetal growth in the whole sample.

Periconceptional multiple-micronutrient supplementation and placental function in rural Gambian women: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Maternal micronutrient deficiencies are commonly associated with clinical indicators of placental dysfunction. OBJECTIVE: We tested the hypothesis that periconceptional multiple-micronutrient supplementation (MMS) affects placental function. DESIGN: We conducted a double-blind, randomized, placebo-controlled trial of MMS in 17- to 45-y-old Gambian women who were menstruating regularly and within the previous 3 mo. Eligible subjects were pre-randomly assigned to supplementation with the UNICEF/WHO/United Nations University multiple micronutrient preparation (UNIMMAP) or placebo on recruitment and until they reached their first antenatal check-up or for 1 y if they failed to conceive. Primary outcome measures were midgestational indexes of utero-placental vascular-endothelial function [ratio of plasminogen-activator inhibitor (PAI) 1 to PAI-2 and mean uterine-artery resistance index (UtARI)] and placental active transport capacity at delivery [fetal to maternal measles antibody (MMA) ratio]. RESULTS: We recruited 1156 women who yielded 415 pregnancies, of which 376 met all of the inclusion criteria. With adjustment for gestational age at sampling, there were no differences in PAI-1 to PAI-2 or MMA ratios between trial arms, but there was a 0.02-unit reduction in UtARI between 18 and 32 wk of gestation (95% CI: -0.03, -0.00; P = 0.040) in women taking UNIMMAP. CONCLUSIONS: Placental vascular function was modifiable by periconceptional micronutrient supplementation. However, the effect was small and supplementation did not further affect other variables of placental function. This trial was registered at www.controlled-trials.com as ISRCTN 13687662.