Anemia and suboptimal gestational weight gain (GWG) are associated with adverse maternal and birth outcomes. Limited research indicates that balanced energy-protein (BEP) supplements reduce the ...incidence of inadequate GWG.
We assessed the efficacy of a micronutrient-fortified BEP supplement on the secondary outcomes of anemia, GWG, GWG rate, and GWG in relation to the Institute of Medicine (IOM)’s recommendations, as compared with an iron–folic acid (IFA) tablet.
We conducted a randomized controlled trial in Burkina Faso, among pregnant women (15–40 y old) enrolled at <21 weeks of gestation. Women received either BEP and IFA (intervention) or IFA (control). Hemoglobin (g/dL) concentrations were measured at baseline and the third antenatal care visit (ANC), whereas maternal weight was measured at baseline and all subsequent ∼7-weekly ANCs. GWG (kg) was calculated as a woman’s last weight measurement (at ∼36 weeks of gestation) minus weight at enrollment, whereas GWG rate (kg/wk) was GWG divided by the time between the first and last weight measurements. GWG adequacy (%) was computed as GWG divided by the IOM’s recommendation. Binary outcomes included severely inadequate, inadequate, and excessive GWG. Statistical analyses followed the intention-to-treat principle. Linear regression and probability models were fitted for the continuous and binary outcomes, respectively, adjusting for baseline measurements.
Women in the BEP group tended to have higher, but nonsignificantly different, GWG (0.28 kg; 95% CI: −0.05, 0.58 kg; P = 0.099). Furthermore, there were no significant differences in prenatal anemia prevalence, GWG rate, GWG adequacy, or incidence of inadequate or excessive GWG. Findings were robust to model adjustments and complete case and per protocol analyses.
This trial does not provide evidence that fortified BEP supplementation reduces maternal anemia or increases GWG, as compared with IFA. In conjunction with the small, but positive, effects of maternal BEP supplementation on birth outcomes, our findings warrant the investigation of additional biochemical and postnatal outcomes. This trial was registered at clinicaltrials.gov as NCT03533712.
Nutrition-sensitive agriculture programmes have the potential to improve child nutrition outcomes, but livestock intensification may pose risks related to water, sanitation and hygiene (WASH) ...conditions. We assessed the impact of SELEVER, a nutrition- and gender-sensitive poultry intervention, with and without added WASH focus, on hygiene practices, morbidity and anthropometric indices of nutrition in children aged 2-4 years in Burkina Faso. A 3-year cluster randomised controlled trial was implemented in 120 villages in 60 communes (districts) supported by the SELEVER project. Communes were randomly assigned using restricted randomisation to one of three groups: (1) SELEVER intervention (n = 446 households); (2) SELEVER plus WASH intervention (n = 432 households); and (3) control without intervention (n = 899 households). The study population included women aged 15-49 years with an index child aged 2-4 years. We assessed the effects 1.5-years (WASH substudy) and 3-years (endline) post-intervention on child morbidity and child anthropometry secondary trial outcomes using mixed effects regression models. Participation in intervention activities was low in the SELEVER groups, ranging from 25% at 1.5 years and 10% at endline. At endline, households in the SELEVER groups had higher caregiver knowledge of WASH-livestock risks (∆ = 0.10, 95% confidence interval CI 0.04-0.16) and were more likely to keep children separated from poultry (∆ = 0.09, 95% CI 0.03-0.15) than in the control group. No differences were found for other hygiene practices, child morbidity symptoms or anthropometry indicators. Integrating livestock WASH interventions alongside poultry and nutrition interventions can increase knowledge of livestock-related risks and improve livestock-hygiene-related practices, yet may not be sufficient to improve the morbidity and nutritional status of young children.
Maternal nutritional status is a major determinant of low birth weight and fluctuates across seasons. Seasonality may influence the outcome of prenatal nutrition interventions that aim to enhance ...fetal growth.
This study investigated seasonal modifications of the efficacy of a randomized controlled prenatal nutrition intervention trial in pregnant women to improve fetal growth in rural Burkina Faso.
The second Micronutriments et Santé de la Mère et de l'Enfant study compared a lipid-based nutrient supplement (LNS) fortified with multiple micronutrients (MMNs) to an MMN supplement. Truncated Fourier series were used to characterize seasonality in birth outcomes. Models that included the Fourier series and newborn and maternal characteristics were used to assess seasonal effect modifications of prenatal supplementation on birth outcomes.
Birth weight, birth length, small for gestational age as a proxy for intrauterine growth retardation, and preterm birth were significantly related to date of birth and showed important seasonal variations. LNSs, which supply energy in addition to MMNs, resulted in a significant increase in birth length (+13.5 mm, 95% CI: 6.5, 20.5 mm) at the transition from rain to dry season (September to November) compared to MMNs alone.
The climatologic and agricultural seasonal patterns in Burkina Faso affect the efficacy of prenatal LNSs on birth length. In this context, prenatal MMN supplementation programs should be complemented by energy supplementation during the annual rain season to promote fetal growth. This trial was registered at clinicaltrials.gov as NCT00909974.
Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using ...individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems.
We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies.
We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.
Mefloquine/artesunate has recently been developed as a fixed-dose combination, providing a promising rescue/alternative treatment for malaria during pregnancy. However, limited data are available on ...the effect of pregnancy on its pharmacokinetic properties. This study was conducted to assess the pharmacokinetic properties of mefloquine/carboxymefloquine and artesunate/dihydroartemisinin in pregnant and non-pregnant women with uncomplicated malaria.
Twenty-four women in their second and third trimesters of pregnancy and 24 paired non-pregnant women were enrolled. All patients were treated for uncomplicated Plasmodium falciparum malaria with a standard fixed-dose combination of oral mefloquine and artesunate one daily over 3 days. Frequent blood samples were collected before treatment and at scheduled times post-dose for the drug measurements and pharmacokinetic analyses. The study was registered at www.clinicaltrials.gov (identifier: NCT00701961).
The total median exposure to mefloquine and dihydroartemisinin was not significantly different between the pregnant and non-pregnant women (P>0.05). There was a trend of higher exposure to mefloquine in the pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h × ng/mL; P=0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735600 versus 1499000 h × ng/mL; P<0.001) and the total drug exposure to artesunate was 42% higher during pregnancy (89.0 versus 62.9 h × ng/mL; P=0.039) compared with non-pregnant controls.
The plasma levels of mefloquine and dihydroartemisinin appeared to be similar in both pregnant and non-pregnant women, but there were significant differences in carboxymefloquine and artesunate exposure. The data presented here do not warrant a dose adjustment in pregnant patients, but an extensive analysis of the data could provide a better understanding of these findings.
: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial drugs. This ...might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach.
: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated
malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling.
: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete
conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women, resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver status (alanine aminotransferase) were found to affect the relative bioavailability of artesunate.
: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development, especially in low transmission settings where relative immunity is lower.
: ClinicalTrials.gov NCT00701961 (19/06/2008).
Anemia and suboptimal gestational weight gain (GWG) are associated with adverse maternal and birth outcomes. Limited research indicates that balanced energy-protein (BEP) supplements reduce the ...incidence of inadequate GWG.
We assessed the efficacy of a micronutrient-fortified BEP supplement on the secondary outcomes of anemia, GWG, GWG rate, and GWG in relation to the Institute of Medicine (IOM)'s recommendations, as compared with an iron-folic acid (IFA) tablet.
We conducted a randomized controlled trial in Burkina Faso, among pregnant women (15-40 y old) enrolled at <21 weeks of gestation. Women received either BEP and IFA (intervention) or IFA (control). Hemoglobin (g/dL) concentrations were measured at baseline and the third antenatal care visit (ANC), whereas maternal weight was measured at baseline and all subsequent ∼7-weekly ANCs. GWG (kg) was calculated as a woman's last weight measurement (at ∼36 weeks of gestation) minus weight at enrollment, whereas GWG rate (kg/wk) was GWG divided by the time between the first and last weight measurements. GWG adequacy (%) was computed as GWG divided by the IOM's recommendation. Binary outcomes included severely inadequate, inadequate, and excessive GWG. Statistical analyses followed the intention-to-treat principle. Linear regression and probability models were fitted for the continuous and binary outcomes, respectively, adjusting for baseline measurements.
Women in the BEP group tended to have higher, but nonsignificantly different, GWG (0.28 kg; 95% CI: -0.05, 0.58 kg; P = 0.099). Furthermore, there were no significant differences in prenatal anemia prevalence, GWG rate, GWG adequacy, or incidence of inadequate or excessive GWG. Findings were robust to model adjustments and complete case and per protocol analyses.
This trial does not provide evidence that fortified BEP supplementation reduces maternal anemia or increases GWG, as compared with IFA. In conjunction with the small, but positive, effects of maternal BEP supplementation on birth outcomes, our findings warrant the investigation of additional biochemical and postnatal outcomes. This trial was registered at clinicaltrials.gov as NCT03533712.
Background: Maternal nutritional status is a major determinant of low birth weight and fluctuates across seasons. Seasonality may influence the outcome of prenatal nutrition interventions that aim to ...enhance fetal growth.
Objective: This study investigated seasonal modifications of the efficacy of a randomized controlled prenatal nutrition intervention trial in pregnant women to improve fetal growth in rural Burkina Faso.
Methods: The second Micronutriments et Santé de la Mère et de l'Enfant study compared a lipid-based nutrient supplement (LNS) fortified with multiple micronutrients (MMNs) to an MMN supplement. Truncated Fourier series were used to characterize seasonality in birth outcomes. Models that included the Fourier series and newborn and maternal characteristics were used to assess seasonal effect modifications of prenatal supplementation on birth outcomes.
Results: Birth weight, birth length, small for gestational age as a proxy for intrauterine growth retardation, and preterm birth were significantly related to date of birth and showed important seasonal variations. LNSs, which supply energy in addition to MMNs, resulted in a significant increase in birth length (+13.5 mm, 95% CI: 6.5, 20.5 mm) at the transition from rain to dry season (September to November) compared to MMNs alone.
Conclusions: The climatologic and agricultural seasonal patterns in Burkina Faso affect the efficacy of prenatal LNSs on birth length. In this context, prenatal MMN supplementation programs should be complemented by energy supplementation during the annual rain season to promote fetal growth. This trial was registered at clinicaltrials.gov as NCT00909974.
Background
: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial ...drugs. This might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach.
Methods
: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated
P. falciparum
malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling.
Results
: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete
in vivo
conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women, resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver status (alanine aminotransferase) were found to affect the relative bioavailability of artesunate.
Conclusions
: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development, especially in low transmission settings where relative immunity is lower.
Trial registration
: ClinicalTrials.gov
NCT00701961
(19/06/2008)
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