Over 46% of African pregnant women are anemic. Oral iron is recommended but often suboptimal, particularly late in pregnancy. Intravenous ferric carboxymaltose (FCM) could treat anemia in women in the third trimester in sub-Saharan Africa. In an open-label, individually randomized trial in antenatal clinics in southern Malawi, we randomized 590 women at 27–35 weeks of gestation with capillary hemoglobin <10.0 g dl⁻¹ to FCM (20 mg kg⁻¹ up to 1,000 mg, once at enrollment) or standard of care (60 mg elemental iron, twice daily for 90 days). Participants and their infants were followed to 4 weeks postpartum. Primary outcomes were maternal anemia at 36 weeks’ gestation or delivery (whichever occurred first) and neonatal birthweight. At the primary timepoint, 126 of 270 (46.7%) of women in the FCM group were anemic, compared to 170 of 271 (67.3%) women in the standard-of-care group (PR, 0.74 (95% CI 0.64, 0.87); P = 0.0002). There was no difference between groups in birthweight (mean difference 10.9 g (−65.7, 87.5 g); P = 0.78). No serious infusion-related reactions occurred, and there were no differences in adverse events between groups. In Malawian women in late pregnancy, FCM effectively and safely reduced anemia before childbirth. Australia New Zealand Clinical Trial registration: ANZCTR12621001239853

Background: Anaemia affects more than half of Africa’s pregnancies. Standard care, with oral iron tablets, often fails to achieve results, with compliance and gastrointestinal side-effects being a significant issue. In recent years, intravenous iron formulations have become safe, effective, and quick to administer, allowing the complete iron requirements of pregnancy to be provided in one 15-minute infusion. The Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) will evaluate whether a modern intravenous iron formulation, ferric carboxymaltose (FCM), given once during the second trimester is effective and safe in improving maternal and neonatal outcomes for treatment of moderate to severe anaemia in sub-Saharan Africa. The objective was to publish the detailed statistical analysis plan for the REVAMP trial prior to unblinding the allocated treatments and performing the analysis. Methods: REVAMP is a multicentre, two-arm, open-label, parallel-group randomized control trial (RCT) in 862 pregnant women in their second trimester. The trial statistician developed the statistical analysis plan in consultation with the trial management team based on the protocol, data collection forms, and study outcomes available in the blinded study database. Results: The detailed statistical analysis plan will support the statistical analyses and reporting of the REVAMP trial after unblinding the treatment allocations. Conclusions: A statistical analysis plan allows for transparency as well as reproducibility of reporting and statistical analyses.

Background Anemia affects 40% of pregnant women globally, leading to maternal mortality, premature birth, low birth weight, and poor baby development. Iron deficiency causes over 40% of anemia cases in Africa. Oral iron supplementation is insufficient for Low-and-Middle-Income-Countries (LMICs) to meet current WHO targets. We hypothesized that a single intravenous dose of Ferric Carboxymaltose (FCM) may be more effective than oral iron treatment for anemia recovery, particularly in these settings where women present late for antenatal care. Methods This is a two-arm parallel open-label individual-randomized controlled trial in third trimester, in malaria Rapid Diagnostic Test-negative pregnant women with moderate or severe anemia - capillary hemoglobin <10 g/dL – who are randomized to receive either parenteral iron – with FCM – or standard-of-care oral iron for the remainder of pregnancy. This is the sister trial to the second-trimester REVAMP trial, funded by the Bill and Melinda Gates Foundation (trial registration ACTRN12618001268235, Gates Grant number INV-010612). In REVAMP-TT, recruitment and treatment are performed within primary health centers. The trial will recruit 590 women across Zomba district, Malawi. The primary outcome is the proportion of anemic women - venous hemoglobin <11 g/dL - at 36 weeks’ gestation or delivery (whichever occurs first). Other pre-specified key secondary clinical and safety outcomes include maternal iron-status and hypophosphatemia, neonate birth weight, infant growth and infant iron and hematological parameters. Discussion This study will determine whether FCM, delivered within primary health centers, is effective, safe and feasible for treating moderate to severe anemia in third-trimester pregnant Malawian women. This intervention could have long-term benefits for maternal and child health, resulting in improved survival and child development.

Research Findings: Optimal sleep is important for children’s learning and development. Sleep disordered breathing (SDB) refers to a spectrum of conditions from simple snoring to obstructive sleep apnea that is common in childhood and interrupts sleep. We examined pathways between SDB and academic performance of children (N = 163, M age = 6.2 years) one year after school entry. Measures included parent questionnaire and clinical assessment of SDB, standardized tests and rating scales of cognitive and executive functioning, researcher-administered literacy and numeracy tasks, and teacher-reported academic performance. Structural equation modeling (SEM) revealed direct and indirect paths between SDB and poorer academic performance. In indirect models, children’s SDB severity score was significantly linked to poorer executive functioning (β = .38, p < .01) and negatively associated with nonverbal reasoning (β = −.21, p < .01). Poorer executive functioning, in turn, was negatively related to the verbal composite (β = −.61, p < .01), with verbal and nonverbal composites associated with academic performance (βs = .56, .27, respectively, p’s < .01). Practice or Policy: These findings point to the need for attention to SDB and its links to potential cognitive sequelae across early development. Practitioners equipped with knowledge of SDB symptoms can facilitate referral for appropriate consultation and evaluation.

The antenatal role of the hepcidin-regulating protease Tmprss6 has never been elucidated because knockout dams are infertile. Using an in vivo knockdown approach, we confirm Tmprsss6 is critical for hepcidin suppression in pregnancy, and Tmprss6 inhibition drives deleterious fetal outcomes.