Effects of an iodine-containing prenatal multiple micronutrient on maternal and infant iodine status and thyroid function:a randomised trial in The Gambia

Background: Iodine supplementation is recommended to pregnant women in iodine-deficient populations, but the impact in moderate iodine deficiency is uncertain. We assessed the effect of an iodine-containing prenatal multiple micronutrient (MMN) supplement in a rural Gambian population at risk of moderate iodine deficiency. Materials and Methods: This study uses data and samples collected as a part of the randomized controlled trial Early Nutrition and Immune Development (ENID; ISRCTN49285450) conducted in Keneba, The Gambia. Pregnant women (<20 weeks gestation) were randomized to either a daily supplement of MMNs containing 300 μg of iodine or an iron and folic acid (FeFol) supplement. Randomization was double blinded (participants and investigators). The coprimary outcomes were maternal urinary iodine concentration (UIC) and serum thyroglobulin (Tg), assessed at baseline and at 30 weeks' gestation. Secondary outcomes were maternal serum thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4) (assessed at baseline and at 30 weeks' gestation), breast milk iodine concentration (BMIC) (assessed at 8, 12, and 24 weeks postpartum), infant serum Tg (assessed at birth [cord], 12, and 24 weeks postpartum), and serum TSH (assessed at birth [cord]). The effect of supplementation was evaluated using mixed effects models. Results: A total of 875 pregnant women were enrolled between April 2010 and February 2015. In this secondary analysis, we included women from the MMN (n = 219) and FeFol (n = 219) arm of the ENID trial. At baseline, median (interquartile range or IQR) maternal UIC and Tg was 51 μg/L (33–82) and 22 μg/L (12–39), respectively, indicating moderate iodine deficiency. Maternal MMN supplement increased maternal UIC (p < 0.001), decreased maternal Tg (p < 0.001), and cord blood Tg (p < 0.001) compared with FeFol. Maternal thyroid function tests (TSH, TT3, TT4, and TT3/TT4 ratio) and BMIC did not differ according to maternal supplement group over the course of the study. Median (IQR) BMIC, maternal UIC, and infant Tg in the MMN group were 51 μg/L (35–72), 39 μg/L (25–64), and 87 μg/L (59–127), respectively, at 12 weeks postpartum, and did not differ between supplement groups. Conclusions: Supplementing moderately iodine-deficient women during pregnancy improved maternal iodine status and reduced Tg concentration. However, the effects were not attained postpartum and maternal and infant iodine nutrition remained inadequate during the first six months after birth. Consideration should be given to ensuring adequate maternal status through pregnancy and lactation in populations with moderate deficiency

Following the World Health Organization's Recommendation of Exclusive Breastfeeding to 6 Months of Age Does Not Impact the Growth of Rural Gambian Infants.

BACKGROUND: The WHO recommends exclusive breastfeeding (EBF) for the first 6 mo of life. OBJECTIVE: The objective of this study was to assess the benefit of EBF to age 6 mo on growth in a large sample of rural Gambian infants at high risk of undernutrition. METHODS: Infants with growth monitoring from birth to 2 y of age (n = 756) from the ENID (Early Nutrition and Immune Development) trial were categorized as exclusively breastfed if only breast milk and no other liquids or foods were given. EBF status was entered into confounder-adjusted multilevel models to test associations with growth trajectories by using >11,000 weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) z score observations. RESULTS: Thirty-two percent of infants were exclusively breastfed to age 6 mo. The mean age of discontinuation of EBF was 5.2 mo, and growth faltering started at ∼3.5 mo of age. Some evidence for a difference in WAZ and WHZ was found between infants who were exclusively breastfed to age 6 mo (EBF-6) and those who were not (nEBF-6), at 6 and 12 mo of age, with EBF-6 children having a higher mean z score. The differences in z scores between the 2 groups were small in magnitude (at 6 mo of age: 0.147 WAZ; 95% CI: -0.001, 0.293 WAZ; 0.189 WHZ; 95% CI: 0.038, 0.341 WHZ). No evidence for a difference between EBF-6 and nEBF-6 infants was observed for LAZ at any time point (6, 12, and 24 mo of age). Furthermore, a higher mean WLZ at 3 mo of age was associated with a subsequent higher mean age at discontinuation of EBF, which implied reverse causality in this setting (coefficient: 0.060; 95% CI: 0.008, 0.120). CONCLUSION: This study suggests that EBF to age 6 mo has limited benefit to the growth of rural Gambian infants. This trial was registered at http://www.isrctn.com as ISRCTN49285450

Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

The prenatal environment can alter an individual's developmental trajectory with long-lasting effects on health. Animal models demonstrate that the impact of the early life environment extends to subsequent generations, but there is a paucity of data from human populations on intergenerational transmission of environmentally induced phenotypes. Here we investigated the association of parental exposure to energy and nutrient restriction in utero on their children's growth in rural Gambia. In a Gambian cohort with infants born between 1972 and 2011, we used multiple regression to test whether parental season of birth predicted offspring birth weight (n = 2097) or length (n = 1172), height-for-age z score (HAZ), weight-for-height z score (WHZ), and weight-for-age z score (WAZ) at 2 yr of age (n = 923). We found that maternal exposure to seasonal energy restriction in utero was associated with reduced offspring birth length (crude:-4.2 mm, P = 0.005; adjusted: -4.0 mm, P = 0.02). In contrast, paternal birth season predicted offspring HAZ at 24 mo (crude: -0.21, P = 0.005; adjusted: -0.22, P = 0.004) but had no discernible impact at birth. Our results indicate that periods of nutritional restriction in a parent's fetal life can have intergenerational consequences in human populations. Fetal growth appears to be under matriline influence, and postnatal growth appears to be under patriline intergenerational influences.-Eriksen, K. G., Radford, E. J., Silver, M. J., Fulford, A. J. C., Wegmüller, R., Prentice, A. M. Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia

Breastfeeding practices and policies in WHO European Region Member States

Abstract Objective: To provide an update on current practices and policy development status concerning breastfeeding in the WHO European Region. Design: National surveys and studies conducted by national health institutions were prioritized. Sub-national data were included where no national data or studies existed. Information on national breastfeeding policies was collected mainly from the WHO Seventh Meeting of Baby-Friendly Hospital Initiative Coordinators and European Union projects. Owing to the different data sources and methods, any comparisons between countries must be made with caution. Setting: WHO European Member States. Results: Data from fifty-three WHO European Member States were investigated; however, a large proportion had not reported any data. Rates of early initiation of breastfeeding, exclusive breastfeeding and continued breastfeeding to 1 year all varied considerably within the WHO European Region. Exclusive breastfeeding rates declined considerably after 4 months, and were low in infants under 6 months and at 6 months of age. The majority of the countries with existing data reported having a national infant and young child feeding policy and the establishment of a national committee on breastfeeding or infant and young child feeding. The majority of the countries with existing data reported having babyfriendly hospitals, although the proportion of baby-friendly hospitals to the total number of national hospitals with maternity units was low in most countries. Conclusions: Breastfeeding practices within the WHO European Region, especially exclusive breastfeeding rates, are far from complying with the WHO recommendations. There are marked differences between countries in breastfeeding practices, infant and young child feeding policy adoption and proportion of baby-friendly hospitals

Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation

We have investigated the function of human topoisomerase 1 (TOP1) in regulation of G-quadruplex (G4) formation in the Pu27 region of the MYC P1 promoter. Pu27 is among the best characterized G4 forming sequences in the human genome and it is well known that promoter activity is inhibited upon G4 formation in this region. We found that TOP1 downregulation stimulated transcription from a promoter with wildtype Pu27 but not if the G4 motif in Pu27 was interrupted by mutation(s). The effect was not specific to the MYC promoter and similar results were obtained for the G4 forming promoter element WT21. The other major DNA topoisomerases with relaxation activity, topoisomerases 2α and β, on the other hand, did not affect G4 dependent promoter activity. The cellular studies were supported by in vitro investigations demonstrating a high affinity of TOP1 for wildtype Pu27 but not for mutant sequences unable to form G4. Moreover, TOP1 was able to induce G4 formation in Pu27 inserted in double stranded plasmid DNA in vitro. This is the first time TOP1 has been demonstrated capable of inducing G4 formation in double stranded DNA and of influencing G4 formation in cells

The Global Nutrition Report 2014: Actions and Accountability to Accelerate the World’s Progress on Nutrition

In 2013, the Nutrition for Growth Summit called for a Global Nutrition Report (GNR) to strengthen accountability in nutrition so that progress in reducing malnutrition could be accelerated. This article summarizes the results of the first GNR. By focusing on undernutrition and overweight, the GNR puts malnutrition in a new light. Nearly every country in the world is affected by malnutrition, and multiple malnutrition burdens are the ‘‘new normal.’’ Unfortunately, the world is off track to meet the 2025 World Health Assembly (WHA) targets for nutrition. Many countries are, however, making good progress on WHA indicators, providing inspiration and guidance for others. Beyond the WHA goals, nutrition needs to be more strongly represented in the Sustainable Development Goal (SDG) framework. At present, it is only explicitly mentioned in 1 of 169 SDG targets despite the many contributions improved nutritional status will make to their attainment. To achieve improvements in nutrition status, it is vital to scale up nutrition programs. We identify bottlenecks in the scale-up of nutrition-specific and nutrition-sensitive approaches and highlight actions to accelerate coverage and reach. Holding stakeholders to account for delivery on nutrition actions requires a well-functioning accountability infrastructure, which is lacking in nutrition. New accountability mechanisms need piloting and evaluation, financial resource flows to nutrition need to be made explicit, nutrition spending targets should be established, and some key data gaps need to be filled. For example, many UN member states cannot report on their WHA progress and those that can often rely on data >5 y old. The world can accelerate malnutrition reduction substantially, but this will require stronger accountability mechanisms to hold all stakeholders to account. J Nutr doi: 10.3945/jn.114.206078

Impaired growth in rural Gambian infants exposed to aflatoxin: a prospective cohort study

Background: Exposure to aflatoxin, a mycotoxin produced by fungi that commonly contaminates cereal crops across sub-Saharan Africa, has been associated with impaired child growth. We investigated the impact of aflatoxin exposure on the growth of Gambian infants from birth to two years of age, and the impact on insulin-like growth factor (IGF)-axis proteins. Methods: A subsample (N = 374) of infants from the Early Nutrition and Immune Development (ENID) trial (ISRCTN49285450) were included in this study. Aflatoxin-albumin adducts (AF-alb) were measured in blood collected from infants at 6, 12 and 18 months of age. IGF-1 and IGFBP-3 were measured in blood collected at 12 and 18 months. Anthropometric measurements taken at 6, 12, 18 and 24 months of age were converted to z-scores against the WHO reference. The relationship between aflatoxin exposure and growth was analysed using multi-level modelling. Results: Inverse relationships were observed between lnAF-alb and length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores from 6 to 18 months of age (β = − 0·04, P = 0·015; β = − 0·05, P = 0.003; β = − 0·06, P = 0·007; respectively). There was an inverse relationship between lnAF-alb at 6 months and change in WLZ between 6 and 12 months (β = − 0·01; P = 0·013). LnAF-alb at 12 months was associated with changes in LAZ and infant length between 12 and 18 months of age (β = − 0·01, P = 0·003; β = − 0·003, P = 0·02; respectively). LnAF-alb at 6 months was associated with IGFBP-3 at 12 months (r = − 0·12; P = 0·043). Conclusions: This study found a small but significant effect of aflatoxin exposure on the growth of Gambian infants. This relationship is not apparently explained by aflatoxin induced changes in the IGF-axis