Perinatal intervention strategies providing food with micronutrients to pregnant and breastfeeding women in low- and middle-income countries: A scoping review.

In resource-constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient-fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low- and middle-income countries. We conducted a PubMed search using pre-defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid-based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk-based beverages [n = 2], and local food/snacks [n = 3]) that provided 118-750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost-effectiveness, and incorporation into multi-component interventions.

Factors associated with late diagnosis of cervical cancer at two national referral hospitals, Kenya 2017: A case control study.

Background: Cervical cancer is the leading cause of cancer mortality among women in Kenya. Two thirds of cervical cancer cases in Kenya are diagnosed in advanced stages. We aimed to identify factors associated with late diagnosis of cervical cancer, to guide policy interventions. Methods: An unmatched case control study (ratio 1:2) was conducted among women aged ≥ 18 years with cervical cancer at Kenyatta National and Moi Teaching and Referral Hospitals. We defined a case as patients with International Federation of Gynecology and Obstetrics (FIGO) stage ≥ 2A and controls as those with stage ≤ 1B. A structured questionnaire was used to document exposure variables. We calculated adjusted odds ratio (aOR) to identify any associations. Results: We enrolled 192 participants (64 cases, 128 controls). Mean age 39.2 (±9.3) years, 145 (76 %) were married, 77 (40 %) had primary level education, 168 (88 %) had their first pregnancy ≤ 24 years of age, 85 (44 %) were > para 3 and 150 (78 %) used contraceptives. Late diagnosis of cervical cancer was associated with cost of travel to cancer centres > USD 6.1 (aOR 6.43 95% CI [1.30, 31.72]), age > 50 years (aOR 4.71; 95% CI [1.18, 18.80]), anxiety over cost of cancer care (aOR 5.6; 95% CI [1.05, 32.72]) and ultrasound examination during evaluation of symptoms (aOR 4.89; 95% CI [1.07-22.42]). Previous treatment for gynecological infections (aOR 0.10; 95% CI [0.02, 0.47]) was protective against late diagnosis. Conclusion: Cost of seeking care and the quality of the diagnostic process were important factors in this study. Decentralization of care, innovative health financing solutions and clear diagnostic and referral algorithms for women presenting with gynecological symptoms could reduce late-stage diagnosis in Kenya.

Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial.

INTRODUCTION: Approximately 40% of children aged 6-59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development. METHODS AND ANALYSIS: IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period. ETHICS AND DISSEMINATION: The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12620000386932.

Implementation of a formalized evaluation and planning tool to improve pediatric oncology outcomes in Kenya.

BACKGROUND: Survival from pediatric cancers in low middle-income countries is often very low compared to that of high-income countries due to multifactorial etiologies, including late presentation, delayed diagnosis, difficulty with accessing healthcare, drug unavailability, and treatment abandonment. The St. Jude Pediatric Oncology Facility Integrated Local Evaluation Tool (PrOFILE) was developed to map and evaluate childhood cancer healthcare delivery in individual institutions and entire countries, identifying the strengths and weaknesses, as well as opportunities for advancement of care. PROCEDURE: Using the PrOFILE self-assessment tool, selected Kenyan pediatric oncology facilities entered data into 12 modules: national context, facility and local context, finances and resources, personnel, service capacity, service integration, diagnostics, chemotherapy, supportive care, surgery, radiation therapy, and patients and outcomes. These modules are grouped into five specific components, including Context, Workforce, Diagnostics, Therapy, and Patients and Outcomes. The St. Jude PrOFILE team analyzed the data and organized the first hybrid workshop, containing both in-person and virtual components. RESULTS: Multidisciplinary stakeholders prioritized recommendations for improving care and developed smart objectives to accomplish identified goals over the following 2 years. Strengths and weaknesses of conducting a hybrid global workshop were identified. CONCLUSIONS: We demonstrated successful use of the PrOFILE tool to conduct a hybrid workshop and identify strategies to improve pediatric oncology care in Kenya. The voluntarily structured work groups will methodically aim to achieve outcome-oriented goals moving forward.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

BACKGROUND: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION: In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING: Bill & Melinda Gates Foundation (INV-010612).

Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

Protocol and statistical analysis plan for a randomized controlled trial of the effect of intravenous iron on anemia in Malawian pregnant women in their third trimester (REVAMP - TT).

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.

Absorption of iron from edible house crickets: a randomized crossover stable-isotope study in humans.

BACKGROUND: Edible insects are a novel source of animal protein. Moreover, edible insects contain iron concentrations similar to meat, potentially making them a valuable iron source for human consumers. Yet, it is unknown to what extent iron from insects is absorbed in humans. OBJECTIVES: In this exploratory study, we assessed fractional iron absorption from house crickets (Acheta domesticus) consumed with refined (low-phytate, noninhibiting) or nonrefined (high-phytate, inhibiting) meals. METHODS: Intrinsically [57Fe]-labeled and control crickets were reared. Six iron-balanced experimental meals were randomly administered crossover to 20 iron-depleted females (serum ferritin <25 µg/L; 18-30 y old), in 2 time-blocks of 3 consecutive days, 2 wk apart. Three meals consisted of refined maize flour porridge with either [57Fe]-labeled crickets, [58Fe]SO4 (reference meal), or unlabeled crickets plus [54Fe]SO4. The other 3 meals consisted of nonrefined maize flour porridge with the same respective additions. Blood samples were drawn to assess the 14-d isotope enrichment in erythrocytes, and meal-specific fractional iron absorption was calculated. In vitro digestion was used to explore possible explanations for unexpected findings. RESULTS: Mean fractional iron absorption from 57Fe-labeled house crickets with refined maize porridge (3.06%) and from refined maize porridge with unlabeled crickets (4.92%) was lower than from the reference meal (14.2%), with respective mean differences of -11.1% (95% CI: -12.6%, -9.68%) and -9.29% (95% CI: -10.8%, -7.77%). Iron absorption from all meals based on unrefined maize porridge was low (<3%), and did not differ for the 2 meals with crickets compared with the reference meal. In vitro digestion showed that chitin, chitosan, and calcium limited iron bioaccessibility to a large extent. CONCLUSIONS: Iron absorption from house crickets and fortified maize porridge with crickets is low, which may be explained by the presence of chitin and other inhibitors in the cricket biomass.This trial was registered at https://www.trialregister.nl as NL6821.

An implementation research programme to support an intravenous iron intervention for pregnant women with moderate and severe anaemia in Malawi: study protocol.

BACKGROUND: Antenatal iron supplementation is critical to maternal and child health; however, access and adherence to oral iron are inconsistent in many low- and middle-income countries (LMICs). Modern intravenous (IV) iron products have become available in high-income clinical settings and provide an opportunity to deliver high doses of iron in a single-short infusion during pregnancy. However, there is limited knowledge of the drivers and barriers for such an intervention to be effectively delivered and upscaled in LMICs. In this study protocol, we describe the implementation research programme to support an IV iron intervention in Malawi for pregnant women with moderate and severe anaemia. METHODS: The implementation research programme has three phases, each guided by implementation science conceptual frameworks. In Phase 1, we will conduct formative research (context assessment of the health system with key informant interviews) to determine how IV iron can be effectively introduced into routine antenatal care. We will use the findings to co-develop potential strategies with end-users and healthcare providers to improve intervention implementation. In Phase 2, we will disseminate the implementation strategies to support the uptake and delivery of the intervention in the study settings. In Phase 3, the intervention will be implemented, and we will conduct formative evaluation (interviews with end-users, healthcare providers, and analysis of health services data) to investigate the feasibility and acceptability of the intervention and strategies. We will also identify processes and contextual factors that facilitate or impede the delivery and uptake of IV iron. DISCUSSION: In LMICs, modern IV iron products present a novel opportunity to rapidly cure moderate and severe anaemia in pregnancy, thereby improving maternal and child health outcomes. This implementation research programme will provide guidance and recommendations on how best an IV iron intervention for pregnant women with anaemia can be implemented in an LMIC setting like Malawi. We will develop locally relevant and culturally appropriate implementation strategies by engaging with key stakeholders (pregnant women, healthcare providers, and policymakers) and identifying factors likely to facilitate successful implementation. The findings of this research can guide the implementation of an IV iron intervention in Malawi and other LMICs.

Reliability and validity of depression anxiety stress scale (DASS)-21 in screening for common mental disorders among postpartum women in Malawi.

BACKGROUND: Approximately one in five women who have recently given birth suffer from common mental disorder (CMD), particularly depression and/or anxiety. Most available CMD screening tools in most low- and middle-income countries do not screen for more than one mental health problem. Having a screening tool that is free to use, short in assessment time, and used to screen for more than one CMD is appealing in a resource-constrained setting. METHOD: We conducted a criterion validation study of the Chichewa translated and adapted DASS-21 instrument against gold standard diagnoses of depression and anxiety disorders using an independently administered Structured Clinical Interview for DSM-IV (SCID). We compared the performance of the DASS-depression subscale with the Edinburgh Postpartum Depression Scale (EPDS). Internal reliability was reported using both Cronbach's alpha and ordinal alpha. The DASS-21 and EPDS ability to discriminate cases from non-cases was assessed by receiver operating characteristics (ROC) analysis. We selected cut-off points for DASS-21 and EPDS that maximise both sensitivity and specificity. RESULTS: One hundred fifteen participants were administered all the measures. Approximately 11.3% and 14.8% had depression and anxiety diagnoses respectively using SCID. The overall Cronbach's alpha for the DASS-21 scale was 0.74. The DASS-21 subscales had Cronbach's alpha values of 0.66, 0.29 and 0.52 for depression (DASS-D), anxiety (DASS-A) and stress (DASS-S), respectively. The ordinal alpha for DASS-D, DASS-A and DASS-S subscales were 0.83, 0.74 and 0.87, respectively. The area under the ROC curve was 0.76 (95% CI: 0.61; 0.91) for DASS-D and 0.65 for DASS-A. At a cut-off point of one or more, the sensitivity and specificity for DASS-D were 69.2% and 75.5%, whilst DASS-A was 52.9% and 75.5%, respectively. Pearson correlation coefficient for the association between DASS-D and EPDS was r = 0.61, p < 0.001. CONCLUSION: The DASS-21 had good internal reliability (Cronbach's alpha), and its ordinal alpha demonstrated good internal reliability for all its sub-scales. Regarding the criterion validation, only the DASS-D and EPDS demonstrated a satisfactory ability to discriminate cases from non-cases. Our findings suggest that health practitioners can use DASS-D as an alternative tool in screening depression as it has fewer questions than EPDS.

Effect of postpartum anaemia on maternal health-related quality of life: a systematic review and meta-analysis.

BACKGROUND: Postpartum anaemia remains a persistent and severe public health issue in many parts of the world. Studies have reported mixed findings on the effects of anaemia during the postpartum period on maternal health-related quality of life (HRQoL). We conducted this systematic review to summarise available evidence to inform public health practitioners on whether 1) anaemia negatively impact maternal health-related quality of life and 2) whether iron supplementation in anaemic women can improve maternal HRQoL during the postpartum period. METHODS: This review's protocol was registered online with PROSPERO (CRD42020206618). We extensively searched Embase, PubMed, Cochrane and Scopus through the HINARI website to identify studies that reported either association or effect of postpartum anaemia on fatigue, depression and mother-child interaction. We restricted our search to studies of human females published in English language from databases inception until August 2020. We followed a Cochrane guideline for reporting systematic reviews and meta-analysis to synthesise data. RESULTS: Twenty-seven studies were included in this systematic review, with some reporting all three domains (fatigue, depression and mother-child interaction) of HRQoL. Seven observational studies with pooled dichotomous outcomes showed that iron deficient or anaemic women were 1.66 times more likely to experience symptoms of depression than non-anaemic or iron-replete women [RR = 1.66 (95% CI: 1.28; 2.16), I2 = 67.0%, P < 0.01]. In three randomized controlled trials (RCTs), pooled continuous data showed statistically significant reduction in fatigue scores in women who received iron supplementation than the control group [MD: -1.85 (95% CI: -3.04; -0.67), I2 = 65.0%, p < 0.06]. Two of the four included studies showed that anaemic mothers were less responsive and had negative feelings towards their children than non-anaemic mothers. CONCLUSION: Evidence from this review suggests that postpartum anaemia negatively affects health-related quality of life and that iron replenishment improves both symptoms of fatigue and depression. Nevertheless, it remains unclear whether postpartum anaemia affects mother-child interaction.

Iron Bioavailability from Infant Cereals Containing Whole Grains and Pulses: A Stable Isotope Study in Malawian Children.

BACKGROUND: Compared with infant cereals based on refined grains, an infant cereal containing whole grains (WGs) and pulses with adequate amounts of ascorbic acid to protect against absorption inhibitors could be a healthier source of well-absorbed iron. However, iron absorption from such cereals is uncertain. OBJECTIVE: We measured iron bioavailability from ferrous fumarate (Fefum) added to commercial infant cereals containing 1) refined wheat flour (reference meal), 2) WG wheat and lentil flour (WG-wheat-lentil), 3) WG wheat and chickpea flour (WG-wheat-chickpeas), and 4) WG oat flour (WG-oat) and from ferrous bisglycinate (FeBG) added to the same oat-based cereal (WG-oat-FeBG). METHODS: In a prospective, single-blinded randomized crossover study, 6- to 14-mo-old Malawian children (n = 30) consumed 25-g servings of all 5 test meals containing 2.25 mg stable isotope-labeled iron and 13.5 mg ascorbic acid. Fractional iron absorption (FIA) was assessed by erythrocyte incorporation of isotopes after 14 d. Comparisons were made using linear mixed models. RESULTS: Seventy percent of the children were anemic and 67% were iron deficient. Geometric mean FIA percentages (-SD, +SD) from the cereals were as follows: 1) refined wheat, 12.1 (4.8, 30.6); 2) WG-wheat-lentil, 15.8 (6.6, 37.6); 3) WG-wheat-chickpeas, 12.8 (5.5, 29.8); and 4) WG-oat, 9.2 (3.9, 21.5) and 7.4 (2.9, 18.9) from WG-oat-FeBG. Meal predicted FIA (P ≤ 0.001), whereas in pairwise comparisons, only WG-oat-FeBG was significantly different compared with the refined wheat meal (P = 0.02). In addition, FIAs from WG-wheat-lentil and WG-wheat-chickpeas were significantly higher than from WG-oat (P = 0.002 and P = 0.04, respectively) and WG-oat-FeBG (P < 0.001 and P = 0.004, respectively). CONCLUSION: In Malawian children, when given with ascorbic acid at a molar ratio of 2:1, iron bioavailability from Fefum-fortified infant cereals containing WG wheat and pulses is ≈13-15%, whereas that from FeBG- and Fefum-fortified infant cereals based on WG oats is ≈7-9%.

Perceptions and experiences of intravenous iron treatment for anaemia in pregnancy in Malawi: a formative qualitative study.

Background: The study objective was to explore opinions, identify experiences, and describe perspectives on the acceptability of intravenous (IV) iron to treat anaemia in pregnancy and identify potential barriers and facilitators of introducing IV iron in the Malawian healthcare system. Methods: We conducted 15 in-depth interviews and two focus group discussions with pregnant women, and seven in-depth interviews with health workers at a community-based health centre in Blantyre and a tertiary hospital in Zomba. Results: Most women who used IV iron treatment during the second trimester of pregnancy reported feeling better and stronger after receiving the intervention. Women perceived that IV iron treatment worked faster than oral iron tablets and increased their haemoglobin count. However, cultural beliefs that IV iron treatment will cause miscarriage and the perception that study procedures involved Satanism and vampirism practices were barriers to acceptability. Health workers found IV iron treatment easy to administer because it is a single-dose treatment, simultaneously reducing the burden for pregnant women taking daily oral iron tablets. However, health workers expressed concerns about the costs and the need to train health workers before the large-scale implementation and integration of IV iron treatment into Malawi's routine care. Conclusions: Despite the perceived concerns and challenges experienced in participating in the first IV iron infusion trial in Malawi, participants' reflections suggest that IV iron infusion is acceptable for treating iron-deficiency anaemia in pregnancy. Participant advocate groups can offer a peer-to-peer education approach to sensitize and engage community members on the benefits of treatment and dispel concerns when the country contemplates integrating IV iron infusion for treating anaemia in pregnancy in Malawi.

Access to Medicines for Non-Communicable Diseases (NCDS) during COVID-19 in Kenya: A Descriptive Commentary.

Evidence shows that those with non-communicable diseases (NCDs) are at higher risk for serious illness and mortality from COVID-19. In Kenya, about 50% of the COVID-19 patients who have died had an NCD. We sought to describe the challenges faced in accessing NCD medicines in Kenya during the pandemic, through a descriptive narrative informed by key stakeholders engaged in NCD service delivery and decision-making. Access to NCD medicines was affected at three levels, service delivery, health facility information systems and the medicines supply chain to health facilities. In response to these gaps, the Ministry of Health released clear directives and interim guidelines for continuity of NCD service delivery. However, implementation of guidelines was not apparent from conversations with county officials or from assessment of county services by the Ministry. Rather, heterogeneity was observed in counties' responsiveness to patient needs, where 5 out of 13 counties used mHealth technologies, while 5 had no established system to reach patients. COVID-19 amplified gaps that already existed in the system-particularly around lack of robust supply chains and sub-optimal health information systems. This descriptive paper will be useful to policy makers to provide a summary of the key challenges faced in accessing NCD medicines, identify gaps in medicines delivery, and make case for establishment of a more equitable health system to meet the needs of lower-income NCD patients.

Protocol for a multicentre, parallel-group, open-label randomised controlled trial comparing ferric carboxymaltose with the standard of care in anaemic Malawian pregnant women: the REVAMP trial.

INTRODUCTION: Anaemia in pregnancy remains a critical global health problem, affecting 46% of pregnant women in Africa and 49% in Asia. Oral iron therapy requires extended adherence to achieve correction of anaemia and replenishment of iron stores. Ferric carboxymaltose (FCM) is a recently established intravenous iron formulation associated with substantial advantages in safety, speed of delivery and total dose deliverable in a single infusion. We aim to determine whether FCM given once during the second trimester of pregnancy compared with standard oral iron distributed through routine antenatal services is effective and safe for treatment of moderate to severe maternal anaemia in sub-Saharan Africa. METHODS AND ANALYSIS: The randomized controlled trial of the effect of intravenous iron on anaemia in Malawian pregnant women (REVAMP) is a two-arm confirmatory individually randomised trial set in Blantyre and Zomba districts in Malawi. The trial will randomise 862 women in the second trimester of pregnancy with a capillary haemoglobin concentration below 100.0 g/L. The study comprises two arms: (a) intravenous FCM (20 mg/kg up to 1000 mg) given once at randomisation, and (b) standard of care oral iron (65 mg elemental iron two times per day) for 90 days (or the duration of pregnancy, whichever is shorter) provided according to local healthcare practices. Both arms receive sulfadoxine-pyrimethamine as intermittent preventive treatment in pregnancy. The primary outcome is the prevalence of anaemia (Hb <110.0 g/L) at 36 weeks' gestation. Secondary outcomes include birth weight, gestation duration and safety outcomes, including clinical malaria, serious perinatal events and postpartum haematologic and health-related outcomes in the mother and child. ETHICS AND DISSEMINATION: Ethical approval was granted by the Research Ethics Committee (COMREC P.02/18/2357) in Malawi and the Human Research Ethics Committee (WEHI: 18/02), Melbourne, Australia. The protocol is registered with the Australian and New Zealand Clinical Trials Registry. The results will be shared with the local community that enabled the research, and also to the international fora. TRIAL REGISTRATION NUMBER: ACTRN12618001268235; Pre-results.

Obesity and risk for hypertension and diabetes among Kenyan adults: Results from a national survey.

ABSTRACT: Despite the anticipated growth in the global burden of obesity especially in low-income countries, limited data exist on the contribution of obesity to cardiometabolic diseases in Africa.We examined population-based samples of Kenyan adults who participated in the 2015 national chronic disease risk factor surveillance survey. Weight and height were measured, and body mass index (BMI) was calculated and used as a measure for general obesity. Waist circumference (WC), a clinical measure of central obesity was also measured. Logistic regression was used to assess the association between obesity with hypertension, diabetes, and dyslipidemia risk.Of the 4276 participants, the median (IQR) age was 36 (27-47) years, 41% were men. One-third (37%) of the participants were centrally obese, whereas 10% were generally obese. The odds for overweight and general obesity were highest among females, adults >40 years, and those in the highest wealth quartile. Central and general obesity, assessed by WC and BMI, were associated with hypertension and dyslipidemia but not diabetes for both sexes. Compared with adults of normal weight, individuals with a BMI of ≥30 kg/m2 had an odds ratio of 2.39 (95% confidence interval [CI], 1.82-3.12) for hypertension and 2.24 (95% CI, 1.70-2.96) for dyslipidemia.Obesity prevalence is high in Kenya and is associated with hypertension and dyslipidemia but not diabetes. Our findings indicate an urgent need to develop public health interventions to address obesity and prevent the development of comorbid conditions.

Iron deficiency anaemia in sub-Saharan Africa: a review of current evidence and primary care recommendations for high-risk groups.

The epidemiology of iron deficiency anaemia in sub-Saharan Africa differs from that in other parts of the world. The low-quality diets prevalent in this region are a poor source of iron, the population is frequently exposed to infection, and demographic characteristics result in a greater prevalence of people at high risk of iron deficiency anaemia than in other parts of the world. We herein review the causes, disease burden, and consequences of iron deficiency anaemia in the general population in this region, and current policies and interventions for its control. The current debate is dominated by concerns about the safety of iron interventions, namely regarding its effects on malaria and other infectious diseases. However, universal antenatal iron supplementation and delayed cord clamping are safe interventions and stand out for their potential to improve maternal and infant health. Effective infection control is a precondition to safe and efficacious iron interventions in children. Greater emphasis should be given to approaches aiming to reduce iron loss due to helminth infections and menstruation, alongside interventions to increase iron intake. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Assessment of small-intestine permeability in healthy Nigerian children is altered by urinary volume and voiding status.

OBJECTIVE: This study aimed to uncover the effect of voided urinary volume on small intestine permeability ratios in healthy children. METHODS: We assessed small intestine permeability in 155 apparently healthy children, aged 3-5 years old, without any visible symptoms of disease, in a rural, malaria-endemic setting in Nigeria, using a multi-sugar test solution, comprising lactulose, sucrose, mannitol, and rhamnose. Children were categorized into low urinary volume (LV) and high urinary volume (HV), based on the volume of urine voided per kg body weight per hour. LV children voided less than 25th percentile of the total population, while HV children voided greater than 75th percentile of the total population. Urinary volume excreted over a 90-minute period after administration of the test solution was measured, and differences in sugar ratios were compared between children with high (HV) and low urinary volumes (LV), as well as between children who voided (VC) or who were not able to void (NVC) before administration of the test solution. RESULTS: Urinary mannitol and rhamnose recovery were 44% (p = 0.002) and 77% (p<0.001) higher in HV children compared to LV children respectively, while urinary lactulose recovery was 34% lower (p = 0.071). There was no difference in urinary sucrose recovery between groups (p = 0.74). Lactulose-mannitol ratio, lactulose-rhamnose ratio and sucrose-rhamnose ratio were all significantly higher in children in the LV group compared to children in the HV group (p<0.001). In a multiple regression analysis, urinary volume and voiding status combined, explained 13%, 23% and 7% of the variation observed in lactulose-mannitol, lactulose-rhamnose and sucrose-rhamnose ratios, respectively. CONCLUSION: Sugar permeability ratios vary significantly with total urinary volume in multi-sugar small-intestine permeability tests. Voiding status before sugar administration appears to influence lactulose recovery, lactulose-rhamnose and sucrose-rhamnose ratios independently of total urinary volume. Evidence from this study suggests the need to take urinary volume into account when conducting multi-sugar small-intestine permeability tests.

Preanalytic and analytic factors affecting the measurement of haemoglobin concentration: impact on global estimates of anaemia prevalence.

The accuracy of haemoglobin concentration measurements is crucial for deriving global anaemia prevalence estimates and monitoring anaemia reduction strategies. In this analysis, we examined and quantified the factors affecting preanalytic and analytic variation in haemoglobin concentrations. Using cross-sectional data from three field studies (in children, pregnant and nonpregnant women), we examined the difference in haemoglobin concentration between venous-drawn and capillary-drawn blood measured by HemoCue (ie, preanalytic) and modelled how the bias observed may affect anaemia prevalence estimates in population surveys and anaemia public health severity classification across countries. Using data from an international quality assurance programme, we examined differences due to instrumentation from 16 different haematology analyzers (ie, analytic). Results indicated that capillary and venous haemoglobin concentrations are not in agreement (bias +5.7 g/L (limits of agreement (LoA) -11.2, 22.6) in preschool age children; range from -28 g/L to +20 g/L in pregnant women; bias +8.8 g/L (LoA -5.2, 22.9) in non-pregnant women). The bias observed could introduce changes in population survey estimates of anaemia of up to -20.7 percentage points in children and -28.2 percentage points in non-pregnant women after venous adjustment. Analytic variation was minimal and unlikely to influence the diagnosis of anaemia. These findings suggest that global estimates of anaemia prevalence derived from capillary haemoglobin, as they often are, may be inaccurate and lead to erroneous public health severity classification, but that point-of-care, or other, instruments should not introduce variation if properly used.

Antenatal iron supplementation, FGF23, and bone metabolism in Kenyan women and their offspring: secondary analysis of a randomized controlled trial.

BACKGROUND: Fibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring. OBJECTIVES: We aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation. METHODS: We performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations ≥ 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13-23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study, we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23). RESULTS: Analysis was performed on 433 women (n = 216, iron group; n = 217, placebo group) and 414 neonates (n = 207, iron group; n = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: -0.3%, 28.4%, P = 0.06), respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: -11.0, -1.2 nmol/L). CONCLUSIONS: Analysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia.