Introduction: Vitamin D plays an important role in brain development in experimental studies; however, the effect of vitamin D deficiency on child development remains inadequately characterized. We aimed to estimate the effects of vitamin D deficiency on neurobehavioural outcomes in children up to 18 years of age. Methods: We searched PubMed, EMBASE, PsycINFO, Scopus, Cochrane Library, Web of Science and Open Grey for published studies up to 10th January 2020. We included all studies that assessed the effects of maternal or child vitamin D status or vitamin D supplementation on neurobehavioural outcomes in children. Study findings were synthesized qualitatively as the high level of heterogeneity in study populations and methodologies precluded a quantitative meta-analysis. Results: Our search identified 5,633 studies, of which 32 studies with 31,445 participants from 18 countries were included in the systematic review. Of the studies identified, two were randomized controlled trials (RCTs) of vitamin D supplementation in children, while 30 were observational. One RCT (n=55) reported a beneficial effect of supplementation with lower doses compared to higher doses of vitamin D on motor development while the other RCT (n=70) found no beneficial effect of vitamin D supplementation on cognition in extremely preterm infants. Twelve mother-child studies (n=17,136) and five studies in children (n=1,091) reported an association between low maternal or child 25-hydroxyvitamin D levels and impaired neurobehavioural outcomes in children, while 15 mother-child studies (n=20,778) and eight studies in children (n=7,496) reported no association. Conclusions: Although animal studies point to an effect of vitamin D deficiency on brain development, there are few studies on the effects of vitamin D deficiency on neurobehavioural outcomes in children and their findings are inconsistent. There is a need for well-conducted, adequately powered studies to further determine these effects in children. Registration: PROSPERO ID CRD42018087619 ; registered on 15 February 2018.

The Millennium Developmental Goals ensured a significant reduction in childhood mortality. However, this reduction simultaneously raised concerns about the long-term outcomes of survivors of early childhood insults. This systematic review focuses on the long-term neurocognitive and mental health outcomes of neonatal insults (NNI) survivors who are six years or older. Two independent reviewers conducted a comprehensive search for empirical literature by combining index and free terms from the inception of the databases until 10^th October 2019. We also searched for additional relevant literature from grey literature and using reference tracking. Studies were included if they: were empirical studies conducted in humans; the study participants were followed at six years of age or longer; have an explicit diagnosis of NNI, and explicitly define the outcome and impairment. Medians and interquartile range (IQR) of the proportions of survivors of the different NNI with any impairment were calculated. A random-effect model was used to explore the estimates accounted for by each impairment domain. Fifty-two studies with 94,978 participants who survived NNI were included in this systematic review. The overall prevalence of impairment in the survivors of NNI was 10.0% (95% CI 9.8–10.2). The highest prevalence of impairment was accounted for by congenital rubella (38.8%: 95% CI 18.8–60.9), congenital cytomegalovirus (23.6%: 95% CI 9.5–41.5), and hypoxic-ischemic encephalopathy (23.3%: 95% CI 14.7–33.1) while neonatal jaundice has the lowest proportion (8.6%: 95% CI 2.7–17.3). The most affected domain was the neurodevelopmental domain (16.6%: 95% CI 13.6–19.8). The frequency of impairment was highest for neurodevelopmental impairment [22.0% (IQR = 9.2–24.8)] and least for school problems [0.0% (IQR = 0.0–0.00)] in any of the conditions. The long-term impact of NNI is also experienced in survivors of NNI who are 6 years or older, with impairments mostly experienced in the neurodevelopmental domain. However, there are limited studies on long-term outcomes of NNI in sub-Saharan Africa despite the high burden of NNI in the region. Registration number: CRD42018082119.

Children living in Sub-Saharan Africa are vulnerable to developmental delay, particularly in the critical first five years due to various adverse exposures including disease and nutritional deficiencies. Anemia and iron deficiency (ID) are highly prevalent in pregnant mothers and young children and are implicated in abnormal brain development. However, available evidence on the association between anemia, ID and neurodevelopment in sub-Saharan Africa is limited. Using data from the Entebbe Mother and Baby Study prospective birth cohort, we examined the effect of maternal and child hemoglobin (Hb) levels and child iron status on developmental scores in 933 and 530 pre-school Ugandan children respectively. Associations between Hb levels, iron status and developmental scores were assessed using regression analyses adjusting for potential confounders. Lower maternal and child Hb levels were associated with reduced psychomotor scores at 15 months, while only lower Hb levels in infancy were associated with reduced language scores. We found no evidence that anemia or ID was associated with cognitive or motor scores at five years. This study emphasizes the importance of managing anemia in pregnancy and infancy and highlights the need for further studies on the effects of anemia and ID in children living in Sub-Saharan Africa.

Vitamin D deficiency is common worldwide and young children are among the most affected groups. Animal studies suggest a key role for vitamin D in brain development. However, studies investigating the effects of vitamin D on neurobehavioural outcomes in children are inconclusive and evidence is limited in sub-Saharan Africa. We evaluated the effect of vitamin D status on cognitive and motor outcomes using prospective data from the Entebbe Mother and Baby Study birth cohort. We analysed data from 302 Ugandan children with 25-hydroxyvitamin D (25(OH)D) measurements below five years and developmental measures at five years of age. We used multivariable linear regression, adjusted for potential confounders, to estimate the effect of 25(OH)D on cognitive and motor outcomes. Of 302 children, eight (2.7%) had 25(OH)D levels 75 nmol/L. There was no evidence that earlier vitamin D status was associated with cognitive and motor outcomes in five-year-old Ugandan children. This study adds to the sparse literature and highlights the need for further longitudinal studies on vitamin D and neurobehavioural outcomes in children living in sub-Saharan Africa.

Background:Iron deficiency and developmental delay are common in African children. While experimental studies indicate an important role of iron in brain development, effects of iron on child development remain unclear. We aimed to evaluate the effects of iron supplementation or fortification on neurobehavioural outcomes in African children and further summarise these effects in children living in non-African countries for comparison. Methods:We searched PubMed, EMBASE, PsycINFO, Scopus and Cochrane Library for studies published up to 22ndOctober 2021. We included randomised controlled trials (RCTs) evaluating effects of iron supplementation or fortification on neurobehavioural outcomes in children. Due to heterogeneity in study methods, we analysed all studies qualitatively and in secondary analyses only seven RCTs with 11 arms were meta-analysed. Results:We identified 2231 studies and included 35 studies (n=9988) in the systematic review. Only five studies (n=1294) included African children while 30 (n=8694) included children living in non-African countries. Of the five African studies, two (n=647) reported beneficial effects of iron supplementation on neurobehavioural outcomes in anaemic children, while three (n=647) found no beneficial effects. Of 30 studies in children living in non-African countries, 10 (n=3105) reported beneficial effects of iron supplementation or fortification on neurobehavioural outcomes, seven (n=786) reported beneficial effects only in children who had iron deficiency, iron deficiency anaemia or anaemia while 13 (n=4803) reported no beneficial effects. Conclusions:There are few studies in African children despite the high burden of iron deficiency and developmental delay in this population. Evidence on the effects of iron supplementation on neurobehavioural outcomes remains unclear and there is need for further well-powered studies evaluating these effects in African populations. PROSPERO registration:CRD42018091278 (20/03/2018)

Children living in Sub-Saharan Africa are vulnerable to developmental delay, particularly in the critical first five years due to various adverse exposures including disease and nutritional deficiencies. Anaemia and iron deficiency (ID) are highly prevalent in pregnant mothers and young children and are implicated in abnormal brain development. However, available evidence on the association between anaemia, ID and neurodevelopment in Sub-Saharan Africa is limited. Using data from the Entebbe Mother and Baby Study prospective birth cohort, we examined the effect of maternal and child haemoglobin (Hb) levels and child iron status on developmental scores in 933 and 530 pre-school Ugandan children respectively. Associations between Hb levels, iron status and developmental scores were assessed using regression analyses adjusting for potential confounders. Lower maternal and child Hb levels were associated with reduced psychomotor scores at 15 months, while only lower Hb levels in infancy were associated with reduced language scores. We found no evidence that anaemia or ID was associated with cognitive or motor scores at five years. This study emphasizes the importance of managing anaemia in pregnancy and infancy and highlights the need for further studies on the effects of anaemia and ID in children living in Sub-Saharan Africa.