Moshood O. Omotayo

Calcium Supplementation to Prevent Preeclampsia: Translating Guidelines into Practice in Low-Income Countries

The WHO issued a strong recommendation that pregnant women be provided calcium supplements to prevent preeclampsia. This is the first recommended nutritional intervention to prevent this condition, a leading cause of maternal mortality globally. As health systems seek to implement this new intervention, a number of issues require further clarification and guidance, including dosage regimen, supplement formulation, and alignment with other antenatal nutritional interventions. We summarize key evidence on the above points and offer our views on good practices. Most developing countries have low calcium intake, so where habitual calcium intake is unknown, calcium supplements are likely beneficial. In our view, policymakers and program planners should consider adopting doses between 1.0 and 1.5 g elemental calcium/d, depending on the local average and variation in dietary calcium intake, logistical feasibility, and acceptability in the target population. Prudent practice would entail daily administration as calcium carbonate administered in divided doses of not >500 mg elemental calcium per dose. For ease of prescribing and adherence, calcium [as with iron and folic acid (IFA)] should be administered routinely to pregnant women from the earliest contact in pregnancy until delivery. Calciums acute inhibitory effect on iron absorption translates to minimal effects in clinical studies. Therefore, to simplify the regimen and facilitate adherence, providers should not counsel that calcium and IFA pills must be taken separately. Although further research will shed more light on clinical and programmatic issues, policies can be implemented with ongoing revision as we continue to learn what works to improve maternal and newborn health.

Cluster-randomized non-inferiority trial to compare supplement consumption and adherence to different dosing regimens for antenatal calcium and iron-folic acid supplementation to prevent preeclampsia and anaemia: rationale and design of the Micronutrient Initiative study

Background: To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca) intake, the World Health Organisation (WHO) recommends routine Ca supplementation during antenatal care (ANC). WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA) supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose) regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. Design and methods: This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill) and IFA (60 mg Fe + 400 µg folic acid) taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill) with IFA taken as above. Measurements: Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Statistical analyses: Unit of randomization is the healthcare facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. Expected public health impact: If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources. Significance for public health Pre-eclampsia is a leading cause of maternal mortality. Based on clinical evidence of significant reduction in risk of pre-eclampsia, the WHO recommends including calcium (Ca) supplementation in antenatal care services in settings with inadequate dietary Ca intakes. A high daily amount of Ca administered in a complex dosing regimen is recommended to maximize efficacy and bioavailability. Factors such as client adherence, motivation, cost and logistical complexities may undermine effectiveness when implemented in public health programs. This cluster-randomized trial will compare Ca supplement consumption between higher and lower-dose regimens delivered through antenatal care in Kenya, integrated with iron-folic acid supplementation. If a lower-dose regimen improves adherence, women’s Ca supplement consumption may be comparable to that achieved under a complex, higher-dose regimen. Evidence gained from this trial will guide public health planning for antenatal calcium supplementation programs to maximize benefits through reducing logistical, cost and adherence barriers.

Perinatal Mortality Due to Pre-Eclampsia in Africa: A Comprehensive and Integrated Approach Is Needed.

See related article by Hodgins. In a recent Global Health: Science and Practice editorial, Hodgins identified key steps to “take a big chunk out of the wedge of maternal, newborn, and stillbirth mortality attributable to eclampsia/pre-eclampsia,” calling for early case identification with more frequent antenatal care (ANC) contacts, effective management of complications in pregnant women that progress to life-threatening states, and timely delivery.1 The editorial is an important call to action and we agree with its proposals; however, there are complementary programmatic issues that must also be considered in crafting an integrated strategy for addressing the burden of perinatal morbidity and mortality attributable to hypertensive disorders in pregnancy in Africa. These include: (a) strengthening management of preterm neonates, (b) strengthening delivery of secondary prevention through ANC, and (c) integrating primary prevention into ANC delivery.

Adherence partners are an acceptable behaviour change strategy to support calcium and iron‐folic acid supplementation among pregnant women in Ethiopia and Kenya

Antenatal calcium and iron-folic acid (IFA) supplementation can reduce maternal mortality and morbidity. Yet, even when pregnant women have a stable supply of supplements, forgetting is often a barrier to adherence. We assessed the acceptability of adherence partners to support calcium and IFA supplementation among pregnant women in Kenya and Ethiopia. Adherence partners are a behaviour change strategy to improve adherence, where pregnant women are counselled to select a partner (e.g. spouse, relative) to remind them to take their supplements. We conducted trials of improved practices, a formative research method that follows participants over time as they try a new behaviour. We provided pregnant women in Ethiopia (n = 50) and Kenya (n = 35) with calcium and IFA supplements and counselling, and suggested selecting an adherence partner. For each participant, we conducted semi-structured interviews about acceptability and adherence during four interviews over six weeks. We analysed interview transcripts thematically and tallied numerical data. In Kenya, 28 of 35 women agreed to try an adherence partner; almost all selected their husbands. In Ethiopia, 42 of 50 women agreed to try an adherence partner; half asked their husbands, others asked children or relatives. Most women who did not select adherence partners reported not needing help or not having anyone to ask. Participants reported adherence partners reminded and encouraged them, brought supplements, provided food and helped address side-effects. Almost all women with adherence partners would recommend this strategy to others. Adherence partners are an acceptable, low-cost strategy with the potential to support antenatal micronutrient supplementation adherence.

Adherence-Specific Social Support Enhances Adherence to Calcium Supplementation Regimens among Pregnant Women

Background: WHO guidelines recommend integrating calcium supplementation into antenatal care (ANC) alongside iron and folic acid (IFA) to reduce maternal mortality. However, supplementation programs face multiple barriers, and strategies to improve adherence are needed. An adherence partner is someone whom pregnant women ask to support adherence at home.Objectives: This study 1) assessed adherence partner acceptability, feasibility, and associations with calcium and IFA supplement adherence and 2) examined relations between social support and adherence.Methods: This secondary analysis is from a trial integrating calcium supplementation into ANC in Kenya. ANC providers were trained on calcium and IFA supplementation and counseling, provided with behavior change materials, and given adequate supplement supplies. Pregnant women from 16 government health facilities were recruited (n = 1036); sociodemographic and adherence data were collected at baseline and at 4- to 6-wk follow-up visits. Adherence was measured with pill counts and self-reports. Culturally adapted scales measured social support in general and specific to adherence. Mixed-effects regression analyses were used to examine factors associated with adherence partners, social support, and adherence.Results: Most participants received information about adherence partners (91%) and had a partner at follow-up (89%). Participants with adherence partners reported higher adherence support (OR: 2.10; 95% CI: 1.32, 3.34). Mean ± SD adherence was high for calcium (88.3% ± 20.7%) and IFA (86.1% ± 20.9%). Adherence support was positively associated with calcium adherence at follow-up by using pill counts (OR: 2.2; 95% CI: 1.1, 2.6) and self-report data (OR: 1.9; 95% CI: 1.2, 2.9), but there was not a direct relation between adherence partners and adherence.Conclusions: Adherence support enhanced adherence to calcium supplements. The adherence partner strategy was highly acceptable and feasible but warrants further study. This research demonstrates the importance of adherence support and suggests that interventions to increase household-level support for antenatal micronutrient supplementation may be needed to implement the WHO guidelines. This trial was registered at clinicaltrials.gov as NCT02238704.

A Simplified Regimen Compared with WHO Guidelines Decreases Antenatal Calcium Supplement Intake for Prevention of Preeclampsia in a Cluster-Randomized Noninferiority Trial in Rural Kenya

Background: To prevent preeclampsia, the WHO recommends antenatal calcium supplementation in populations with inadequate habitual intake. The WHO recommends 1500-2000 mg Ca/d with iron-folic acid (IFA) taken separately, a complex pill-taking regimen. Objective: The objective of this study was to test the hypothesis that simpler regimens with lower daily dosages would lead to higher adherence and similar supplement intake.Methods: In the Micronutrient Initiative Calcium Supplementation study, we compared the mean daily supplement intake associated with 2 dosing regimens with the use of a parallel, cluster-randomized noninferiority trial implemented in 16 primary health care facilities in rural Kenya. The standard regimen was 3 × 500 mg Ca/d in 3 pill-taking events, and the low-dose regimen was 2 × 500 mg Ca/d in 2 pill-taking events; both regimens included a 200 IU cholecalciferol and calcium pill and a separate IFA pill. We enrolled 990 pregnant women between 16 and 30 wk of gestation. The primary outcome was supplemental calcium intake measured by pill counts 4 and 8 wk after recruitment. We carried out intention-to-treat analyses with the use of mixed-effect models, with regimen as the fixed effect and health care facilities as a random effect, by using a noninferiority margin of 125 mg Ca/d.Results: Women in facilities assigned to the standard regimen consumed a mean of 1198 mg Ca/d, whereas those assigned to the low-dose regimen consumed 810 mg Ca/d. The difference in intake was 388 mg Ca/d (95% CI = 341, 434 mg Ca/d), exceeding the prespecified margin of 125 mg Ca/d. The overall adherence rate was 80% and did not differ between study arms.Conclusions: Contrary to our expectation, a simpler, lower-dose regimen led to significantly lower supplement intake than the regimen recommended by the WHO. Further studies are needed to precisely characterize the dose-response relation of calcium supplementation and preeclampsia risk and to examine cost effectiveness of lower and simpler regimens in program settings. This trial was registered at clinicaltrials.gov as NCT02238704.

“I Can’t Answer What You’re Asking Me. Let Me Go, Please.”: Cognitive Interviewing to Assess Social Support Measures in Ethiopia and Kenya

Cognitive interviewing is a method to develop culturally appropriate survey questions and scale items. We conducted two rounds of cognitive interviews with 24 pregnant women in Ethiopia and Kenya to assess the appropriateness, acceptability, and comprehension of general and micronutrient supplement adherence-specific social support scales. We stopped the first round of cognitive interviews after receiving negative feedback from interviewers and participants about their distressing and uncomfortable experiences with cognitive probes and challenges related to cultural perspectives on social support. Through an iterative process, we made substantial changes to the cognitive interview guides and items from both social support scales. In the second round, the revised cognitive interviewing process substantially improved interviewer and participant experiences and increased comprehension and appropriateness of both social support scales. This study confirms the importance of cultural adaptation of the cognitive interviewing process as well as social support scales.

Geophagic earths consumed by women in western Kenya contain dangerous levels of lead, arsenic, and iron

Geophagy is commonly reported by pregnant women and children, yet its causes and consequences remain poorly understood. Therefore, we sought to determine if geophagy could contribute micronutrients and/or be a source of heavy metal exposure by examining the elemental composition of earths consumed in Kakamega, Kenya.