Background: Innovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women. Methods and findings: This was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) ≤23.0 cm presenting for antenatal care at one of 43 government health clinics in Western Rural Area and Pujehun districts were eligible for participation. Standard of care included a blended corn/soy flour and intermittent preventive treatment for malaria in pregnancy (IPTp). The intervention replaced the blended flour with RUSF and added azithromycin and testing and treatment for vaginal dysbiosis. Since the study involved different foods and testing procedures for the intervention and control groups, no one except the authors conducting the data analyses were blinded. The primary outcome was birth length. Secondary outcomes included maternal weight gain, birth weight, and neonatal survival. Follow-up continued until 6 months postpartum. Modified intention to treat analyses was undertaken. Participants were enrolled and followed up from February 2017 until February 2020. Of the 1,489 women enrolled, 752 were allocated to the intervention and 737 to the standard of care. The median age of these women was 19.5 years, of which 42% were primigravid. Twenty-nine women receiving the intervention and 42 women receiving the standard of care were lost to follow-up before pregnancy outcomes were obtained. There were 687 singleton live births in the intervention group and 657 in the standard of care group. Newborns receiving the intervention were 0.3 cm longer (95% confidence interval (CI) 0.09 to 0.6; p = 0.007) and weighed 70 g more (95% CI 20 to 120; p = 0.005) than those receiving the standard of care. Those women receiving the intervention had greater weekly weight gain (mean difference 40 g; 95% CI 9.70 to 71.0, p = 0.010) than those receiving the standard of care. There were fewer neonatal deaths in the intervention (n = 13; 1.9%) than in the standard of care (n = 28; 4.3%) group (difference 2.4%; 95% CI 0.3 to 4.4), (HR 0.62 95% CI 0.41 to 0.94, p = 0.026). No differences in adverse events or symptoms between the groups was found, and no serious adverse events occurred. Key limitations of the study are lack of gestational age estimates and unblinded administration of the intervention. Conclusions: In this study, we observed that the addition of RUSF, azithromycin, more frequent IPTp, and testing/treatment for vaginal dysbiosis in undernourished pregnant women resulted in modest improvements in anthropometric status of mother and child at birth, and a reduction in neonatal death. Implementation of this combined intervention in rural, equatorial Africa may well be an important, practical measure to reduce infant mortality in this context. Trial registration: ClinicalTrials.gov NCT03079388.

Appropriate nutrition during pregnancy and the post-partum period is vital for both the mothers and their offspring. Both under- and over-nourished status may have important microbial implications on the maternal and infant gut microbiomes. Alterations in the microbiome can have implications for a person’s risk of obesity and metabolic diseases. In this review, we examine alterations in the maternal gut, vaginal, placental, and milk microbiomes in the context of pre-pregnancy BMI, gestational weight gain, body composition, gestational diabetes, and maternal diet. We also investigate how the infant gut microbiome may be altered by these different parameters. Many of the microbial changes seen in under- and over-nourished states in birthing parents may result in long-term implications for the health of offspring. Differences in diet appear to be a major driver of the maternal and subsequently milk and offspring microbiomes. Further prospective longitudinal cohort studies are needed to examine nutrition and the microbiome to better understand its implications. Additionally, trials involving dietary interventions in child-bearing age adults should be explored to improve the mother and child’s risks for metabolic diseases.

Background: Associations of 2-year neurodevelopmental and behavioral outcomes with growth trajectories of preterm infants are unknown. Methods: This secondary analysis of a preterm cohort examined in-hospital and discharge to 2-year changes in anthropometric z-scores. Two-year follow-up included Bayley Scales of Infant Development (BSID-III) and Child Behavior Checklist. Results: Among 590 infants, adjusted in-hospital growth was not associated with any BSID-III subscale. Occipitofrontal circumference (OFC) growth failure (GF) in-hospital was associated with increased adjusted odds of attention problems (aOR 1.65 [1.03, 2.65]), aggressive behavior (aOR 2.34 [1.12, 4.89]), and attention-deficit-hyperactivity symptoms (aOR 1.86 [1.05, 3.30]). Infants with OFC GF at 2 years had lower adjusted BSID-III language scores (−4.0 [−8.0, −0.1]), increased odds of attention problems (aOR 2.29 [1.11, 4.74]), aggressive behavior (aOR 3.09 [1.00, 9.56]), and externalizing problems (aOR 3.01 [1.07, 8.45]) compared to normal OFC growth cohort. Conclusion: Infants with OFC GF are at risk for neurodevelopmental and behavioral impairment. Clinical trial registration: This study is a secondary analysis of pre-existing data from the PENUT Trial Registration: NCT01378273.

Objectives To investigate the feasibility of eye-tracking-based testing of the speed of visual orienting in malnourished young children at rural clinics in Sierra Leone. Design Prospective dual cohort study nested in a cluster-randomised trial. Setting 8 sites participating in a cluster-randomised trial of supplementary feeding for moderate acute malnutrition (MAM). Participants For the MAM cohort, all infants aged 7–11 months at the eight sites were enrolled, 138 altogether. For controls, a convenience sample of all non-malnourished infants aged 7–11 months at the same sites were eligible, 60 altogether. A sample of 30 adults at the sites also underwent eye-tracking tests as a further control. Interventions Infants with MAM were provided with supplementary feeding. Outcome measures The primary outcomes were feasibility and reliability of eye-tracking-based testing of saccadic reaction time (SRT). Feasibility was assessed by the percent of successful tests in the infants. Reliability was measured with intraclass correlation coefficients (ICCs). Secondary outcomes were mean SRT based on nutritional state as well as and changes in mean SRT after supplementary feeding of MAM children. Results Infants exhibited consistent orienting to targets on a computer screen (>95% of valid trials). Mean SRTs had moderate stability within visits (ICCs 0.60–0.69) and across the 4-week test–retest interval (0.53) in infants; the adult control group had greater SRT stability (within visit ICC=0.92). MAM infants had a trend toward higher adjusted SRT at baseline (difference=12.4 ms, 95% CI −2 to 26.9, p=0.09) and improvement in SRT 4 weeks thereafter (difference=−14 ms, 95% CI −26.2 to −1.7, p=0.025) compared with age-matched controls. Conclusions The results demonstrate the feasibility of eye-tracking-based testing in a resource-poor field setting and suggest eye-tracking measures have utility in the detection of group level effects of supplementary feeding.

Previously, a novel oat-ready-to-use therapeutic food (o-RUTF) resulted in improved recovery from severe acute malnutrition (SAM) when compared to standard RUTF (s-RUTF). O-RUTF contained 18% oat, while s-RUTF has no cereal ingredients. We determined the effect of o-RUTF on intestinal permeability, as measured by lactulose permeability, and the 16S rRNA fecal microbiome configuration of children with SAM. This was a prospective, randomized, double-blinded, controlled clinical trial. Sierra Leonean children aged 6–59 months with SAM defined by mid-upper arm circumference < 11.5 cm were randomized to receive o-RUTF or s-RUTF. All children received 7 days amoxicillin per guidelines. Lactulose permeability testing and fecal 16S rRNA sequencing were performed at baseline and after 4 weeks of therapy. Change in lactulose permeability was the primary outcome while fecal 16S rRNA configuration at 4 weeks was a secondary outcome. Of 129 children enrolled, 100 completed baseline and 82 completed week 4 lactulose permeability testing. After 4 weeks of therapeutic feeding, there were no differences in lactulose permeability between children receiving o-RUTF vs. s-RUTF (P = 0.84), and over half of children had increased lactulose permeability (50% s-RUTF vs 58% o-RUTF, mean difference = -7.5%; 95% CI -29.2, 15.2; P = 0.50). After four weeks of feeding, there were no differences in the 16S rRNA configuration between children receiving o-RUTF vs. s-RUTF (Permanova 999 permutations, P = 0.648, pseudo-F = 0.581), nor were there differences in α- or β-diversity. Despite remarkable different compositions of o-RUTF and s-RUTF, no differences were identified in lactulose permeability or the fecal 16S rRNA configuration among children with SAM receiving these foods. These results suggest that the o-RUTF exerts its beneficial effect through mechanisms other than reducing intestinal permeability or altering the fecal 16S configuration. Clinical Trial Registry: The trial was registered at ClinicalTrials.gov (NCT04334538).

Low birth weight (LBW) infants are at increased risk of morbidity and mortality. Identification of LBW may not occur in settings where access to reliable scales is limited. Mid-upper arm circumference (MUAC) may be an accessible, low-cost measure to identify LBW and vulnerable infants. We explored the validity of newborn MUAC in identifying LBW and vulnerable newborns in rural Sierra Leone. This was a secondary analysis of infant data from a randomized, controlled clinical trial of a supplementary food and anti-infective therapies compared to standard care for undernourished pregnant women. Singleton live-born infants with birth measurements and 6-month survival data were included in this analysis. The primary outcome was validity of MUAC in identifying low birth weight (LBW) neonates. Secondary outcomes included validity of MUAC and head circumference (HC) in identifying WLZ ←2, LAZ ←2, neonatal mortality and mortality within the first 6 months of life. 1167 infants with 229 (19.6%) LBW were the study population. Birth MUAC (r = 0.817) and HC (r = 0.752) were highly correlated with birth weight. MUAC (Area-under-the-curve = 0.905, 95% CI 0.884 to 0.925) performed superior to HC (Area-under-the-curve = 0.88, 95% CI 0.856 to 0.904) in identifying LBW. The MUAC for identifying LBW was 9.6 cm(sensitivity = 0.86, specificity = 0.78). Neither MUAC nor HC reliably identified newborns with WLZ ←2 or LAZ ←2. MUAC ≤ 9.0 cm was the ideal cutoff for neonatal mortality (sensitivity = 53.3%, specificity = 89.7%; HR 9.57, 95% CI 1.86 to 49.30). Birth anthropometrics did not reliably identify infants at risk of death in the first 6-months of life. MUAC identifies LBW infants and infants at-risk of neonatal mortality in Sierra Leone. Further evidence is needed to increase the use of newborn MUAC in community settings where scales are not available. Clinical Trial Registration: The primary trial was registered at ClinicalTrials.gov (NCT03079388).