Effects of Multimicronutrient Supplementation during Pregnancy on Postnatal Growth of Children under 5 Years of Age: A Meta-Analysis of Randomized Controlled Trials

<div><p>Background</p><p>The beneficial effect of antenatal multiple micronutrients supplementation on infant birth outcomes has been proposed by previous meta-analyses. However, their benefits on postnatal health of children have not been summarized. A meta-analysis of randomized controlled trials was conducted to evaluate the effect of maternal multimicronutrient supplementation on postnatal growth of children under 5 years of age.</p><p>Methods</p><p>We searched both published and ongoing trials through the PubMed, EMBASE, CENTRAL (OVID platform), Web of Science, BIOSIS Previews, Chinese Science Citation Database, Scopus, ProQuest, ClinicalTrials.gov, Chinese Biomedical Database, and WANFANG database for randomized controlled trials. Reference lists of included studies and relevant reviews were also reviewed for eligible studies. Standard mean difference (SMD) was employed as the index for continuous variables by using fixed effects models. Trend analysis by visual inspection was applied to evaluate the change of mean difference of weight and height between the groups over time.</p><p>Results</p><p>Nine trials (12 titles) from nine different countries were retrieved for analysis. Pooled results showed that antenatal multimicronutrient supplementation increased child head circumference (SMD = 0.08, 95% CI: 0.00–0.15) compared with supplementation with two micronutrient or less. No evidence was found for the benefits of antenatal multimicronutrient supplementation on weight (<i>P</i> = 0.11), height (<i>P</i> = 0.66), weight-for-age z scores (WAZ) (<i>P</i> = 0.34), height-for-age z scores (HAZ) (<i>P</i> = 0.81) and weight-for-height z scores (WHZ) (<i>P</i> = 0.22). A positive effect was found on chest circumference based on two included studies.</p><p>Conclusions</p><p>Antenatal multimicronutrient supplementation has a significant positive effect on head circumference of children under 5 years. No impact of the supplementation was found on weight, height, WAZ, HAZ and WHZ.</p></div

Mean difference of height over time.

<p>Mean difference of height over time.</p

Effect of antenatal multimicronutrient supplementation on child growth under 5 years in randomized controlled trials.

<p>Effect of antenatal multimicronutrient supplementation on child growth under 5 years in randomized controlled trials.</p

Characteristics of the included studies selected for meta-analysis.

1<p>including number of mothers enrolled and number of children whose anthropometric data was provided;</p>2<p>from the enrollment until the final measurement of the children;</p>3<p>time points at which growth of child were measured;</p>4<p>NG means not given;</p>5<p>1–1.5 RDA of several micronutrients, details of the component were not given;</p>6<p>WAZ means weight-for-age z scores;</p>7<p>HAZ means height-for-age z scores;</p>8<p>WHZ means weight-for-height z scores;</p>9<p>UNIMMAP contains 15 vitamins and trace elements. They are vitamin A (800 µg), vitamin E (10 mg), vitamin D (5 µg), vitamin B1 (1.4 mg), vitamin B2 (1.4 mg), niacin (18 mg), vitamin B6 (1.9 mg), vitamin B12 (2.6 µg), folic acid (400 µg), vitamin C (70 mg), iron (30 mg), zinc (15 mg), copper (2 mg), selenium (65 µg), and iodine (150 µg);</p>10<p>there were six intervention groups including UNIMMAP, Fe60F, Fe30F plus early or usual food invitation. Fe60F means 60 mg iron+folic acid; Fe30F means 30 mg iron+folic acid;</p>11<p>the effect of intervention was estimated with mixed effect models;</p>12<p>estimated based on the descriptions from the study;</p>13<p>the effect of the intervention was estimated with mixed effect linear and logistic model;</p>14<p>data was not provided for analysis.</p

Subgroup analysis of the effects of antenatal multimicronutrient supplementation on postnatal child growth.

<p>Subgroup analysis of the effects of antenatal multimicronutrient supplementation on postnatal child growth.</p

Selection of studies included in meta-analysis on antenatal multi-micronutrient supplementations on postnatal child growth under 5 years.

<p>Selection of studies included in meta-analysis on antenatal multi-micronutrient supplementations on postnatal child growth under 5 years.</p

Discovery of 1‑(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)­pyrido[2,3‑<i>d</i>]pyrimidin-6-yl)phenyl)urea (LY3009120) as a Pan-RAF Inhibitor with Minimal Paradoxical Activation and Activity against <i>BRAF</i> or <i>RAS</i> Mutant Tumor Cells

The RAS-RAF-MEK-MAPK cascade is an essential signaling pathway, with activation typically mediated through cell surface receptors. The kinase inhibitors vemurafenib and dabrafenib, which target oncogenic BRAF V600E, have shown significant clinical efficacy in melanoma patients harboring this mutation. Because of paradoxical pathway activation, both agents were demonstrated to promote growth and metastasis of tumor cells with <i>RAS</i> mutations in preclinical models and are contraindicated for treatment of cancer patients with <i>BRAF</i> WT background, including patients with <i>KRAS</i> or <i>NRAS</i> mutations. In order to eliminate the issues associated with paradoxical MAPK pathway activation and to provide therapeutic benefit to patients with <i>RAS</i> mutant cancers, we sought to identify a compound not only active against BRAF V600E but also wild type BRAF and CRAF. On the basis of its superior in vitro and in vivo profile, compound <b>13</b> was selected for further development and is currently being evaluated in phase I clinical studies