Malaria and undernutrition frequently coexist, especially in pregnant women and young children. Nutrient supplementation of these vulnerable groups might reduce their susceptibility to malaria by improving immunity.

Stunting prevalence is an indicator of a country's progress towards United Nations' Sustainable Development Goal 2, which is to end hunger and achieve improved nutrition. Accelerating progress towards reducing stunting requires a deeper understanding of the factors that contribute to linear growth faltering. We conducted path analyses of factors associated with 18-month length-for-age z-score (LAZ) in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements Project in Ghana (n=1039), Malawi (n=684 and 1504) and Burkina Faso (n=2619). In two cohorts, women were enrolled during pregnancy. In two other cohorts, infants were enrolled at 6 or 9 months. We examined the association of 42 indicators of environmental, maternal, caregiving and child factors with 18-month LAZ. Using structural equation modelling, we examined direct and indirect associations through hypothesised mediators in each cohort. Out of 42 indicators, 2 were associated with 18-month LAZ in three or four cohorts: maternal height and body mass index (BMI). Six factors were associated with 18-month LAZ in two cohorts: length for gestational age z-score (LGAZ) at birth, pregnancy duration, improved household water, child dietary diversity, diarrhoea incidence and 6-month or 9-month haemoglobin concentration. Direct associations were more prevalent than indirect associations, but 30%-62% of the associations of maternal height and BMI with 18-month LAZ were mediated by LGAZ at birth. Factors that were not associated with LAZ were maternal iron status, illness and inflammation during pregnancy, maternal stress and depression, exclusive breast feeding during 6 months post partum, feeding frequency and child fever, malaria and acute respiratory infections. These findings may help in identifying interventions to accelerate progress towards reducing stunting; however, much of the variance in linear growth status remained unaccounted for by these 42 individual-level factors, suggesting that community-level changes may be needed to achieve substantial progress.

Previous reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD.

New regimens for intermittent preventive treatment in pregnancy (IPTp) against malaria are needed as the effectiveness of the standard two-dose sulfadoxine-pyrimethamine (SP) regimen is under threat. Previous trials have shown that IPTp with monthly SP benefits HIV-positive primi- and secundigravidae, but there is no conclusive evidence of the possible benefits of this regimen to HIV-negative women, or to a population comprising of both HIV-positive and -negative women of different gravidities.

Background: It is unclear whether maternal supplementation with small-quantity lipid-based nutrient supplements (SQ-LNSs; 118 kcal/d) affects maternal weight.Objective: We compared several secondary anthropometric measures between 3 groups of women in the iLiNS (International Lipid-based Nutrient Supplements)-DYAD trial in Ghana.Methods: Women (n = 1320; <20 wk of gestation) were randomly assigned to receive 60 mg Fe + 400 μg folic acid/d (IFA), 18 vitamins and minerals/d [multiple micronutrients (MMNs)], or 20 g SQ-LNSs with 22 micronutrients/d (LNS) during pregnancy and a placebo (200 mg Ca/d), MMNs, or SQ-LNSs, respectively, for 6 mo postpartum. Weight, midupper arm circumference (MUAC), and triceps skinfold (TSF) thickness at 36 wk of gestation and 6 mo postpartum were analyzed, as were changes from estimated prepregnancy values. We assessed the adequacy of estimated gestational weight gain (GWG) by using Institute of Medicine (IOM) and International Fetal and Newborn Growth Standards for the 21st Century (INTERGROWTH-21st) guidelines.Results: The estimated prepregnancy prevalence of overweight or obesity was 38.5%. By 36 wk of gestation, women (n = 1015) had a mean ± SD weight gain of 7.4 ± 3.7 kg and changes of -1.0 ± 1.7 cm in MUAC and -2.8 ± 4.1 mm in TSF thickness. The LNS group had a lower prevalence of inadequate GWG on the basis of IOM guidelines (57.4%) than the MMN (67.2%) but not the IFA (63.1%) groups (P = 0.030), whereas the prevalence of adequate (26.9% overall) and excessive (10.4% overall) GWG did not differ by group. The percentages of normal-weight women (in kg/m2: 18.5 < body mass index < 25.0; n = 754) whose GWG was less than the third centile of the INTERGROWTH-21st standards were 23.0%, 28.7%, and 28.5% for the LNS, MMN, and IFA groups, respectively (P = 0.36). At 6 mo postpartum, the prevalence of overweight or obesity was 45.3%, and the risk of becoming overweight or obese did not differ by group.Conclusion: SQ-LNS supplementation is one potential strategy to address the high prevalence of inadequate GWG in women in settings similar to Ghana, without increasing the risk of excessive GWG. This trial was registered at clinicaltrials.gov as NCT00970866.

It is unknown whether a novel small-quantity lipid-based nutrient supplement (SQ-LNS) containing alpha-linolenic (ALA) and linoleic acids impacts maternal plasma lipids and fatty acid status. We measured plasma fatty acids (wt%) and lipid concentrations at 36 wk gestation and breast milk fatty acids (wt%) at 6 months postpartum in a subsample of women enrolled in a randomized controlled trial studying the effects of SQ-LNS on birth outcomes and child growth. Women≤20 wk gestation in Ghana (n=1,320) and Malawi (n=1,391) were assigned to receive daily either: 1) iron-folic acid (pregnancy); 2) multiple micronutrients (pregnancy and lactation); or 3) SQ-LNS (pregnancy and lactation). At 36 wk, plasma ALA levels were higher in those receiving SQ-LNS. SQ-LNS increased breast milk ALA in Ghana but not Malawi. There was no effect on plasma lipids or other selected fatty acids. SQ-LNS may impact plasma and breast milk ALA levels depending on the population.

Insufficient calcium intake during pregnancy may lead to maternal bone resorption and lower bone density of offspring. We evaluated the impact of supplementary calcium with or without vitamin D during pregnancy on maternal and offspring bone mineral density (BMD) and teeth firmness of the offspring. Randomized controlled trials (RCTs) were searched systematically in 11 databases. Two researchers independently screened the titles and abstracts of 3555 records and the full texts of 31 records to examine eligibility. The search yielded seven RCTs (11 reports, n = 1566).  No advantage of calcium supplementation was found on maternal BMD after delivery or during breastfeeding, or on offspring BMD, even when dietary calcium intake was low. The results were neither modified by the dose of calcium nor concomitant vitamin D administration. A suspicion of some long-term harm of the intervention on maternal BMD and growth of female offspring was raised based on the data. One study suggested some benefit of high-dose calcium supplementation on offspring teeth firmness at 12 years old. A low number of the studies and abundant missing data reduced the quality of the findings. The impact of calcium supplementation on maternal and offspring bone health was deemed unknown because of inconclusive research results.

Maternal malaria and infections during pregnancy are risk factors for fetal growth restriction. We assessed the impact of preventive treatment in pregnancy on maternal malaria and fetal growth. Between 2003 and 2006, we enrolled 1,320 pregnant Malawian women, 14-26 gestation weeks, in a randomized trial and treated them with two doses of sulfadoxine-pyrimethamine (SP, control) at enrollment and between 28-34 gestation weeks; with monthly SP from enrollment until 37 gestation weeks; or with monthly SP and azithromycin twice, at enrollment and between 28 and 34 gestation weeks (AZI-SP). Participants were seen at 4-week intervals until 36 completed gestation weeks and weekly thereafter. At each visit, we collected dried blood spots for real-time polymerase chain reaction diagnosing of malaria parasitemia and, in a random subgroup of 341 women, we measured fetal biparietal diameter and femur length with ultrasound. For the monthly SP versus the control group, the odds ratios (OR) (95% CI) of malaria parasitemia during the second, third, and both trimesters combined were 0.79 (0.46-1.37), 0.58 (0.37-0.92), and 0.64 (0.42-0.98), respectively. The corresponding ORs for the AZI-SP versus control group were 0.47 (0.26-0.84), 0.51 (0.32-0.81), and 0.50 (0.32-0.76), respectively. Differences between the AZI-SP and the monthly SP groups were not statistically significant. The interventions did not affect fetal biparietal diameter and femur length growth velocity. The results suggest that preventive maternal treatment with monthly SP reduced malaria parasitemia during pregnancy in Malawi and that the addition of azithromycin did not provide much additional antimalarial effect.

Human milk oligosaccharides (HMOs) and bioactive proteins likely benefit infant health, but information on these relations is sparse.

This individually randomized trial was conducted to estimate the effect of promoting community-initiated kangaroo mother care (ciKMC) in low birthweight (LBW) infants on infant breastfeeding performance. It was designed as a substudy within a larger primary trial on ciKMC and infant survival. Five hundred fifty stable LBW mother-infant dyads (1500-2250 g) who provided consent, were consecutively enroled for breastfeeding performance assessment. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding (EBF) through home visits during the neonatal period. The primary outcome was effective breastfeeding performance indicated by an infant breastfeeding assessment tool score of ≥10 after the end of the neonatal period. As secondary outcomes, we reported maternal satisfaction related to infant breastfeeding, and EBF after the end of the neonatal period. We completed outcome assessments in 96% of participants. In the ciKMC arm, 92% of the infants showed effective breastfeeding performance against 81% in the control arm [adjusted prevalence ratio (aPR): 1.24, 95% confidence interval (CI): 1.16-1.32]. In the ciKMC arm, 65% of the mothers reported to be very satisfied with their infants' breastfeeding against 51% in the control arm (aPR: 1.22, 95% CI: 1.05-1.41). The proportion of infants practicing EBF was 89% in the ciKMC arm against 45% in the control arm (aPR: 1.62, 95% CI: 1.45-1.81). Our study findings suggest that promotion of ciKMC can improve effective breastfeeding, EBF and maternal satisfaction related to breastfeeding in LBW infants.

Periodontal disease ranges from gingival inflammation (gingivitis) to the inflammation and loss of tooth-supporting tissues (periodontitis). Previous research has focused mainly on subgingival plaque, but supragingival plaque composition is also known to be associated with disease. Quantitative modeling of bacterial abundances across the natural range of periodontal severities can distinguish which features of disease are associated with particular changes in composition. We assessed a cross-sectional cohort of 962 Malawian women for periodontal disease and used 16S rRNA gene amplicon sequencing (V5 to V7 region) to characterize the bacterial compositions of supragingival plaque samples. Associations between bacterial relative abundances and gingivitis/periodontitis were investigated by using negative binomial models, adjusting for epidemiological factors. We also examined bacterial cooccurrence networks to assess community structure. The main differences in supragingival plaque compositions were associated more with gingivitis than periodontitis, including higher bacterial diversity and a greater abundance of particular species. However, even after controlling for gingivitis, the presence of subgingival periodontitis was associated with an altered supragingival plaque. A small number of species were associated with periodontitis but not gingivitis, including members of Prevotella, Treponema, and Selenomonas, supporting a more complex disease model than a linear progression following gingivitis. Cooccurrence networks of periodontitis-associated taxa clustered according to periodontitis across all gingivitis severities. Species including Filifactor alocis and Fusobacterium nucleatum were central to this network, which supports their role in the coaggregation of periodontal biofilms during disease progression. Our findings confirm that periodontitis cannot be considered simply an advanced stage of gingivitis even when only considering supragingival plaque.

Malnutrition impairs cognitive, communication, and motor development, but it is not known how nutrition and health are associated with development in children with moderate acute malnutrition (MAM). We aimed to describe motor and language development of children with MAM and explore its nutrition and health-related correlates. This cross-sectional study used baseline data from a nutritional trial in children with MAM aged 6-23 months in Burkina Faso. Motor and language skills were assessed using the Malawi Development Assessment Tool (MDAT). Linear mixed models were used to explore potential correlates of MDAT including socio-economic status, anthropometry, body composition, whole-blood polyunsaturated fatty acids (PUFA), haemoglobin (Hb), iron status, and morbidity. We also assessed child and caregiver participation during MDAT procedures and their associations with correlates and development. MDAT data were available for 1.608 children. Mean (95% CI) MDAT z-scores were -0.39 (-0.45, -0.34) for gross motor, 0.54 (0.48, 0.59) for fine motor, and -0.91 (-0.96, -0.86) for language skills. Children with higher mid-upper arm circumference, weight-for-height, height-for-age, fat-free mass, n-3 PUFAs, Hb, and iron status had better MDAT z-scores, whereas children with more fat mass index, anaemia, illness, and inflammation had poorer z-scores. In addition, children living in larger households or with an unmarried mother had poorer MDAT z-scores. Associations between morbidity and z-scores were largely explained by children's poorer participation during MDAT assessment. The identified factors associated with child development may inform interventions needed to stimulate development during or after management of MAM.

Maternal infections are associated with maternal and foetal adverse outcomes. Nutrient supplementation during pregnancy may reduce the occurrence of infections by improving maternal immunity. We aimed to investigate the impact of small-quantity lipid-based nutrient supplement (SQ-LNS) on the occurrence of Plasmodium falciparum parasitaemia during pregnancy and trichomoniasis, vaginal candidiasis and urinary tract infection (UTI) after delivery.

Theoretical and empirical considerations suggest that individual differences in infant visual attention correlate with variations in cognitive skills later in childhood. Here we tested this hypothesis in infants from rural Malawi (n = 198-377, depending on analysis), who were assessed with eye tracking tests of visual orienting, anticipatory looks, and attention to faces at 9 months, and more conventional tests of cognitive control (A-not-B), motor, language, and socioemotional development at 18 months. The results showed no associations between measures of infant attention at 9 months and cognitive skills at 18 months, either in analyses linking infant visual orienting with broad cognitive outcomes or analyses linking specific constructs between the two time points (i.e., switching of anticipatory looks and manual reaching responses), as correlations varied between -0.08 and 0.14. Measures of physical growth, and family socioeconomic characteristics were also not correlated with cognitive outcomes at 18 months in the current sample (correlations between -0.10 and 0.19). The results do not support the use of the current tests of infant visual attention as a predictive tool for 18-month-old infants' cognitive skills in the Malawian setting. The results are discussed in light of the potential limitations of the employed infant tests as well as potentially unique characteristics of early cognitive development in low-resource settings.

It is unknown whether prenatal lipid-based nutrient supplements (LNSs) affect blood pressure (BP). Associations between hypertension and birth outcomes using recently updated BP cutoffs are undetermined.

Human milk oligosaccharides (HMOs) and bioactive proteins are beneficial to infant health. Recent evidence suggests that maternal nutrition may affect the amount of HMOs and proteins in breast milk; however, the effect of nutrient supplementation on HMOs and bioactive proteins has not yet been well studied.

Lipid-based nutrient supplements (LNS) have been found to improve child growth and reduce child mortality. However, the mechanistic pathways for these improvements warrant exploration. One potential pathway is linked to improvement in intestinal health. Our study aimed to test a hypothesis that small-quantity LNS (SQ-LNS) could reduce the levels of intestinal inflammation, repair and permeability of children. As intestinal health markers we measured fecal calprotectin, regenerating 1B protein (REG1B) and alpha-1-antitrypsin concentrations at 18 months of age (after 12 months of supplementation) and 1 year later (12 months after cessation of supplementation). In this analysis, we included data of 735 children who participated in a randomised dietary supplementation trial in rural Malawi; 243 children who received 20 g/day SQ-LNS from 6 to 18 months of age were in the SQ-LNS group, while the others who received no dietary supplementation during this period were in the control group. At 18 months of age, the mean concentrations of calprotectin, REG1B and alpha-1-antitrypsin were 241, 105 µg/g and 7.1 mg/dl, respectively, in the SQ-LNS group, and 224, 105 µg/g and 7.4 mg/dl, respectively, in the control group, and did not differ between the SQ-LNS and control groups. We conclude that SQ-LNS provision did not have an impact on children's intestinal health in rural Malawi.

Little is known about the impact of small-quantity lipid-based nutrient supplements (SQ-LNSs) on maternal morbidity. This secondary outcome analysis aimed to compare morbidity symptoms among women in two trials evaluating the efficacy of SQ-LNSs. From enrolment (≤20-week gestation) to 6 months postpartum, Ghanaian (n = 1320) and Malawian (n = 1391) women were assigned to consume daily: 60 mg iron and 400 µg folic acid until childbirth and placebo thereafter (iron and folic acid [IFA] group); or multiple micronutrients (MMN); or 20 g/day SQ-LNSs. Within country, we used repeated measures logistic regression and analysis of variance models to compare group differences in the period prevalence and percentage of days of monitoring when women had fever, gastrointestinal, reproductive, and respiratory symptoms during the second and third trimesters of pregnancy (n ~ 1243 in Ghana, 1200 in Malawi) and 0-3 and 3-6 months postpartum (n ~ 1212 in Ghana, 730 in Malawi). Most outcomes did not differ significantly among groups, with the following exceptions: in Ghana, overall, the prevalence of vomiting was lower in the LNS (21.5%) than MMN (25.6%) group, with the IFA group (23.2%) in-between (p = 0.046); mean ± SD percentage of days with nausea was greater in the LNS (3.5 ± 10.3) and MMN (3.3 ± 10.4) groups than the IFA (2.7 ± 8.3) group (p = 0.002). In Malawi, during 3-6 month postpartum, the prevalence of severe diarrhoea was greater in the LNS (8.1%) than the MMN (2.9%) group, with IFA (4.6%) in-between, p = 0.041). We conclude that the type of nutrient supplement received during pregnancy and lactation generally does not influence morbidity symptoms in these settings. Clinicaltrials.gov identifiers: NCT00970866; NCT01239693.

Low birth weight (LBW) is a significant public health concern given its association with early-life mortality and other adverse health consequences that can impact the entire life cycle. In many countries, accurate estimates of LBW prevalence are lacking due to inaccuracies in collection and gaps in available data. Our study aimed to determine LBW prevalence among facility-born infants in selected areas of Kenya and Tanzania and to assess whether the introduction of an intervention to improve the accuracy of birth weight measurement would result in a meaningfully different estimate of LBW prevalence than current practice.

Pregnant and post-partum women require increased nutrient intake and optimal cognition, which depends on adequate nutrition, to enable reasoning and learning for caregiving. We aimed to assess (a) differences in maternal cognition and caregiving between women in Malawi who received different nutritional supplements, (b) 14 effect modifiers, and (c) associations of cognition and caregiving with biomarkers of iron, Vitamin A, B-vitamin, and fatty acid status. In a randomized controlled trial (n = 869), pregnant women daily received either multiple micronutrients (MMN), 20 g/day lipid-based nutrient supplements (LNS), or a control iron/folic acid (IFA) tablet. After delivery, supplementation continued in the MMN and LNS arms, and the IFA control group received placebo until 6 months post-partum, when cognition (n = 712), caregiving behaviour (n = 669), and biomarkers of nutritional status (n = 283) were assessed. In the full group, only one difference was significant: the IFA arm scored 0.22 SD (95% CI [0.01, 0.39], p = .03) higher than the LNS arm in mental rotation. Among subgroups of women with baseline low hemoglobin, poor iron status, or malaria, those who received LNS scored 0.4 to 0.7 SD higher than the IFA arm in verbal fluency. Breastmilk docosahexaenoic acid and Vitamin B12 concentrations were positively associated with verbal fluency and digit span forward (adjusting for covariates ps < .05). In this population in Malawi, maternal supplementation with MMN or LNS did not positively affect maternal cognition or caregiving. Maternal docosahexaenoic acid and B12 status may be important for post-partum attention and executive function.