Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial

Background Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa. The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose. Methods This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20–32 weeks’ gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum. Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks’ gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks’ gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions. Discussion The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned. Trial registration ISRCTN registry ISRCTN63484804. Registered on 10 December 2020. Clinicaltrials.govNCT04976179. Registered on 26 July 2021 The current protocol version is version 2.1 (080/080/2021)

Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial.

BACKGROUND: Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa. The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose. METHODS: This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20-32 weeks' gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum. Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks' gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks' gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions. DISCUSSION: The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned. TRIAL REGISTRATION: ISRCTN registry ISRCTN63484804 . Registered on 10 December 2020 Clinicaltrials.gov NCT04976179 . Registered on 26 July 2021 The current protocol version is version 2.1 (080/080/2021)

Analysis of serum placental growth factor levels in preeclamptic and normotensive pregnant women in Lagos, Nigeria: a worthwhile screening tool?

The clinical usefulness of serum placental growth factor (PlGF) as a predictive biomarker of preeclampsia is currently being examined. However, there are still conflicting results in the literature. We assessed the association between maternal low PlGF levels and the occurrence and severity of preeclampsia. This was an analytical cross-sectional study conducted among 60 women with preeclampsia, and an equal number of matched normotensive pregnant women. PlGF concentrations were analysed using the ELISA method. Bivariate and multivariate analysis was used to test for the association between low maternal PlGF levels and the occurrence of preeclampsia and its severity. Statistical significance was reported at p < .05. The study showed that having a low maternal PlGF level (Adjusted OR 14.23; 95%CI 8.06, 29.71) together with being primigravid (Adjusted OR 3.97; 95%CI 1.03, 6.18) and having an unbooked pregnancy (Adjusted OR 8.07; 95%CI 2.06, 19.40) were independently associated with preeclampsia. We established an association between low maternal PlGF levels and preeclampsia, but no similar association with severe preeclampsia. The use of PlGF as a potential predictive marker and a reliable screening tool may have a profound implication on the prevention of preeclampsia and the subsequent reduction in its associated morbidity and mortality.Impact statement What is already known on this subject? The utility of serum placental growth factor (PlGF) as a predictive biomarker of preeclampsia is currently being examined, however, there are conflicting results of its clinical usefulness in the literature. What do the results of this study add? This study that assessed the association between maternal low PlGF levels and the occurrence and severity of preeclampsia showed that having a low maternal PlGF level together with being primigravid and having an unbooked pregnancy were independently associated with the occurrence of preeclampsia. However, we were unable to establish any significant relationship between maternal PlGF and the severity of preeclampsia. What are the implications of these findings for clinical practice and/or further research? We opined that the use of PlGF as a potential predictive marker and a reliable screening tool may have a profound clinical implication on the prevention and reduction in the associated morbidity and mortality of preeclampsia. However, there is an urgent need for more robust longitudinal studies to define the regulation of placental vascular development and the clinical usefulness of maternal serum PlGF and other placental biomarkers as potential screening tools for preeclampsia among black African women

Acceptability of focused antenatal care by pregnant Nigerian women and factors influencing it

Context: In 2002, the World Health Organization (WHO) proposed "Focused Antenatal Care (FANC)"model for developing countries and it is aimed at addressing some of the challenges associated with the traditional model of antenatal care and to improve the quality of antenatal care services rendered. Despite its wide publicity, most teaching hospitals in Nigeria still practice the traditional ANC model, notwithstanding the high level of awareness of the tenet ofFANC among resident doctors.Objective: This study aimed at assessing the acceptability of this new model by Nigerian pregnant women.Methodology: This was a questionnaire-based cross-sectional study conducted at the antenatal clinic at thc Lagos University Teaching Hospital (LUTH). A total of 410 consenting pregnant women at varying gestational ages were recruited for this study. Data collected was analyzed using Epi Info statistical software.Results : The mean age ± S.D. of the subjects was 31.2 ± 4.3 years, with over half of the patients living close to the hospital (56.4%). The mean gestational age± S.D. at booking was 16.0± 6.3 weeks and 54.5% were high risk pregnancy. Over a third (35.1 %) of the women had missed at least 1 - 3 visits. A greater proportion (56.1%) of the pregnant women studied preferred the new model, FANC, while 42.4% indicated preference for the traditional model. The main reason for preferring FANC is convenience (92.2% of respondents). The main reasons for rejecting FANC are that complications can arise in pregnancy at anytime (71.3%) and 4 visits were adjudged to be inadequate (43.7%). Factors influencing thc acceptability of FANC by Nigerian pregnant women were age (p - 0.00(0). tribe (p '" 0.0487), proximity to the hospital (0.0088) and parity (p - 0.0006).Conclusion: Many parturient are ready to accept FANC if given the opportunities. It should thus be offered to highly motivated women especially in urban cities in Nigeria where many educated women reside, but education on birth preparedness and complication readiness needs to be emphasized.Key words: acceptability focused antenatal care, influencing factors

Acceptability of IV iron treatment for iron deficiency anaemia in pregnancy in Nigeria: a qualitative study with pregnant women, domestic decision-makers, and health care providers.

BackgroundAnaemia in pregnancy causes a significant burden of maternal morbidity and mortality in sub-Saharan Africa, with prevalence ranging from 25 to 45% in Nigeria. The main treatment, daily oral iron, is associated with suboptimal adherence and effectiveness. Among pregnant women with iron deficiency, which is a leading cause of anaemia (IDA), intravenous (IV) iron is an alternative treatment in moderate or severe cases. This qualitative study explored the acceptability of IV iron in the states of Kano and Lagos in Nigeria.MethodsWe purposively sampled various stakeholders, including pregnant women, domestic decision-makers, and healthcare providers (HCPs) during the pre-intervention phase of a hybrid clinical trial (IVON trial) in 10 healthcare facilities across three levels of the health system. Semi-structured topic guides guided 12 focus group discussions (140 participants) and 29 key informant interviews. We used the theoretical framework of acceptability to conduct qualitative content analysis.ResultsWe identified three main themes and eight sub-themes that reflected the prospective acceptability of IV iron therapy. Generally, all stakeholders had a positive affective attitude towards IV iron based on its comparative advantages to oral iron. The HCPs noted the effectiveness of IV iron in its ability to evoke an immediate response and capacity to reduce anaemia-related complications. It was perceived as a suitable alternative to blood transfusion for specific individuals based on ethicality. However, to pregnant women and the HCPs, IV iron could present a higher opportunity cost than oral iron for the users and providers as it necessitates additional time to receive and administer it. To all stakeholder groups, leveraging the existing infrastructure to facilitate IV iron treatment will stimulate coherence and self-efficacy while strengthening the existing trust between pregnant women and HCPs can avert misconceptions. Finally, even though high out-of-pocket costs might make IV iron out of reach for poor women, the HCPs felt it can potentially prevent higher treatment fees from complications of IDA.ConclusionsIV iron has a potential to become the preferred treatment for iron-deficiency anaemia in pregnancy in Nigeria if proven effective. HCP training, optimisation of information and clinical care delivery during antenatal visits, uninterrupted supply of IV iron, and subsidies to offset higher costs need to be considered to improve its acceptability. Trial registration ISRCTN registry ISRCT N6348 4804. Registered on 10 December 2020 Clinicaltrials.gov NCT04976179. Registered on 26 July 2021

Prevalence of and risk factors for iron deficiency among pregnant women with moderate or severe anaemia in Nigeria: a cross-sectional study.

BackgroundAnaemia during pregnancy causes adverse outcomes to the woman and the foetus, including anaemic heart failure, prematurity, and intrauterine growth restriction. Iron deficiency anaemia (IDA) is the leading cause of anaemia and oral iron supplementation during pregnancy is widely recommended. However, little focus is directed to dietary intake. This study estimates the contribution of IDA among pregnant women and examines its risk factors (including dietary) in those with moderate or severe IDA in Lagos and Kano states, Nigeria.MethodsIn this cross-sectional study, 11,582 women were screened for anaemia at 20-32 weeks gestation. The 872 who had moderate or severe anaemia (haemoglobin concentration ResultsIron deficiency was observed among 41% (95%CI: 38 - 45) of women with moderate or severe anaemia and the prevalence increased with gestational age. The odds for IDA reduces from aOR: 0.36 (95%CI: 0.13 - 0.98) among pregnant women who consume green leafy vegetables every 2-3 weeks, to 0.26 (95%CI: 0.09 - 0.73) among daily consumers, compared to those who do not eat it. Daily consumption of edible kaolin clay was associated with increased odds of having IDA compared to non-consumption, aOR 9.13 (95%CI: 3.27 - 25.48). Consumption of soybeans three to four times a week was associated with higher odds of IDA compared to non-consumption, aOR: 1.78 (95%CI: 1.12 - 2.82).ConclusionAbout 4 in 10 women with moderate or severe anaemia during pregnancy had IDA. Our study provides evidence for the protective effect of green leafy vegetables against IDA while self-reported consumption of edible kaolin clay and soybeans appeared to increase the odds of having IDA during pregnancy. Health education on diet during pregnancy needs to be strengthened since this could potentially increase awareness and change behaviours that could reduce IDA among pregnant women with moderate or severe anaemia in Nigeria and other countries

Additional file 2 of Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial

Additional file 2. Ethics approval and consent to participate

Additional file 1 of Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial

Additional file 1. SPIRIT checklist