Effects of prenatal food and micronutrient supplementation on child growth from birth to 54 months of age: a randomized trial in Bangladesh

<p>Abstract</p> <p>Background</p> <p>There is a lack of information on the optimal timing of food supplementation to malnourished pregnant women and possible combined effects of food and multiple micronutrient supplementations (MMS) on their offspring's growth. We evaluated the effects of prenatal food and micronutrient interventions on postnatal child growth. The hypothesis was that prenatal MMS and early invitation to food supplementation would increase physical growth in the offspring during 0-54 months and a combination of these interventions would further improve these outcomes.</p> <p>Methods</p> <p>In the large, randomized MINIMat trial (Maternal and Infant Nutrition Interventions in Matlab), Bangladesh, 4436 pregnant women were enrolled between November 2001 and October 2003 and their children were followed until March 2009. Participants were randomized into six groups comprising 30 mg Fe and 400 μg folic acid (Fe30F), 60 mg Fe and 400 μg folic acid (Fe60F) or MMS combined with either an early (immediately after identification of pregnancy) or a later usual (at the time of their choosing, i.e., usual care in this community) program invitation to food supplementation. The anthropometry of 3267 children was followed from birth to 54 months, and 2735 children were available for analysis at 54 months.</p> <p>Results</p> <p>There were no differences in characteristics of mothers and households among the different intervention groups. The average birth weight was 2694 g and birth length was 47.7 cm, with no difference among intervention groups. Early invitation to food supplementation (in comparison with usual invitation) reduced the proportion of stunting from early infancy up to 54 months for boys (p = 0.01), but not for girls (p = 0.31). MMS resulted in more stunting than standard Fe60F (p = 0.02). There was no interaction between the food and micronutrient supplementation on the growth outcome.</p> <p>Conclusions</p> <p>Early food supplementation in pregnancy reduced the occurrence of stunting during 0-54 months in boys, but not in girls, and prenatal MMS increased the proportion of stunting in boys. These effects on postnatal growth suggest programming effects in early fetal life.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN16581394">ISRCTN16581394</a></p

Oestrogen blocks the nuclear entry of SOX9 in the developing gonad of a marsupial mammal

<p>Abstract</p> <p>Background</p> <p>Hormones are critical for early gonadal development in nonmammalian vertebrates, and oestrogen is required for normal ovarian development. In contrast, mammals determine sex by the presence or absence of the <it>SRY </it>gene, and hormones are not thought to play a role in early gonadal development. Despite an XY sex-determining system in marsupial mammals, exposure to oestrogen can override <it>SRY </it>and induce ovarian development of XY gonads if administered early enough. Here we assess the effect of exogenous oestrogen on the molecular pathways of mammalian gonadal development.</p> <p>Results</p> <p>We examined the expression of key testicular (<it>SRY</it>, <it>SOX9</it>, <it>AMH </it>and <it>FGF9</it>) and ovarian (<it>WNT4</it>, <it>RSPO1</it>, <it>FOXL2 </it>and <it>FST</it>) markers during gonadal development in the marsupial tammar wallaby (<it>Macropus eugenii</it>) and used these data to determine the effect of oestrogen exposure on gonadal fate. During normal development, we observed male specific upregulation of <it>AMH </it>and <it>SOX9 </it>as in the mouse and human testis, but this upregulation was initiated before the peak in <it>SRY </it>expression and 4 days before testicular cord formation. Similarly, key genes for ovarian development in mouse and human were also upregulated during ovarian differentiation in the tammar. In particular, there was early sexually dimorphic expression of <it>FOXL2 </it>and <it>WNT4</it>, suggesting that these genes are key regulators of ovarian development in all therian mammals. We next examined the effect of exogenous oestrogen on the development of the mammalian XY gonad. Despite the presence of <it>SRY</it>, exogenous oestrogen blocked the key male transcription factor SOX9 from entering the nuclei of male somatic cells, preventing activation of the testicular pathway and permitting upregulation of key female genes, resulting in ovarian development of the XY gonad.</p> <p>Conclusions</p> <p>We have uncovered a mechanism by which oestrogen can regulate gonadal development through the nucleocytoplasmic shuttling of SOX9. This may represent an underlying ancestral mechanism by which oestrogen promotes ovarian development in the gonads of nonmammalian vertebrates. Furthermore, oestrogen may retain this function in adult female mammals to maintain granulosa cell fate in the differentiated ovary by suppressing nuclear translocation of the SOX9 protein.</p> <p>See commentary: http://www.biomedcentral.com/1741-7007/8/110</p