Search

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

BACKGROUND: In many regions of the world, little is known about meal structures, meal patterns, and nutrient intake because the collection of quantitative dietary intake is expensive and labor-intensive. OBJECTIVES: We describe the development and field feasibility of a tablet-based Tanzania 24-h recall tool (TZ-24hr-DR) and dietary intakes collected from adults and children in rural and urban settings. METHODS: Using the Tanzanian food-composition table, the TZ-24hr-DR tool was developed on an Android platform using the Open Data Kit. The module provides food lists, meal lists, ingredient lists, quantity and amount consumed, breastfeeding frequency, and a recipe feature. Similar to the USDA Automated Multiple Pass Method, this TZ-24hr-DR contains review features such as time in-between meals, a summary of meals, and portion sizes. RESULTS: Dietary intake using TZ-24hr-DR was collected among 1) 845 children 0-18 mo of age enrolled in the Engaging Fathers for Effective Child Nutrition and Development in Tanzania (EFFECTS) trial (ClinicalTrials.gov identifier: NCT03759821) in Mara, Tanzania, and 2) 312 adult families from the Diet, Environment, and Choices of positive living (DECIDE) observational study in peri-urban Dar es Salaam. Interviewers were trained on paper-based methods with food models and tablet-based collection. Conversion to nutrient intake was readily linked and accessible, enabling rapid review and analysis. Overall, 2158 and 8197 dietary meal records were collected from the DECIDE study and EFFECTS trial, respectively. Among adults, 63% of men and 92% of women reported eating at home, and there were differences in protein, fat, and zinc. Food consumed outside the home typically occurs for the first 2 meals. Childrens intake of nutrients increased with age; however, median micronutrient intakes for calcium, iron, zinc, and vitamin A remained below recommended nutrient intakes. CONCLUSIONS: The TZ-24hr-DR is a field- and user-friendly tool that can collect large samples of dietary intakes. Further validation is needed. The tool is available freely for research purposes and can be further adapted to other contexts in East Africa.

Background: Multicomponent interventions are needed to address the various co‐occurring risks that compromise early child nutrition and development. We compared the independent and combined effects of engaging fathers and bundling parenting components into a nutrition intervention on early child development (ECD) and parenting outcomes. Methods: We conducted a 2×2 factorial cluster‐randomized controlled trial across 80 villages in Mara Region, Tanzania, also known as EFFECTS (Engaging Fathers for Effective Child Nutrition and Development in Tanzania; ClinicalTrials.gov, NCT03759821). Households with children under 18 months of age residing with their mother and father were enrolled. Villages were randomly assigned to one of five groups: a nutrition intervention for mothers, a nutrition intervention for couples, a bundled nutrition and parenting intervention for mothers, a bundled intervention for couples, and a standard‐of‐care control. Interventions were delivered by trained community health workers through peer groups and home visits over 12 months. Mothers, fathers, and children were assessed at baseline, midline, and endline or postintervention. We used a difference‐in‐difference approach with intention‐to‐treat analysis to estimate intervention effects on ECD (Bayley Scales of Infant and Toddler Development, third edition) and maternal and paternal parenting and psychosocial well‐being. Results: Between October 29, 2018, and May 24, 2019, 960 households were enrolled (n = 192 per arm). Compared to nutrition interventions, bundled interventions improved children's cognitive (β =.18 [95% CI: 0.01, 0.36]) and receptive language development (β =.23 [0.04, 0.41]). There were no differences between interventions for other ECD domains. Compared to nutrition interventions, bundled interventions achieved additional benefits on maternal stimulation (β =.21 [0.04, 0.38]) and availability of home learning materials (β =.25 [0.07–0.43]) and reduced paternal parenting distress (β = −.34 [−0.55, −0.12]). Compared to interventions with mothers only, interventions that engaged fathers improved paternal stimulation (β =.45 [0.27, 0.63]). Conclusions: Jointly bundling parenting components into nutrition interventions while also engaging both mothers and fathers is most effective for improving maternal and paternal parenting and ECD outcomes. [ABSTRACT FROM AUTHOR]

Background: Globally, 144 million children under 5 years are undernourished and 250 million do not meet their developmental potential. Multi-input interventions, such as bundled nutrition and parenting interventions, are designed to mitigate risks for multiple child outcomes. There is limited evidence that bundled interventions have additive benefits to nutrition, growth, or development outcomes. These outcomes share common risks; therefore, designing interventions to tackle these risks using a common theory of change may optimize effectiveness. Emerging evidence suggests explicit engagement of fathers may benefit child outcomes, but few trials have tested this or included data collected from fathers. Methods: Engaging Fathers for Effective Child Nutrition and Development in Tanzania (EFFECTS) is a community-based cluster-randomized controlled trial that will be implemented in the rural Mara Region, Tanzania. The trial aims (1) to test a bundled nutrition and parenting program delivered to mothers' groups, with or without fathers' groups, over 12 months on child and caregiving outcomes compared to a nutrition program alone, and (2) to test nutrition or bundled nutrition and parenting programs delivered to mothers' and fathers' groups over 12 months on child and caregiving outcomes compared to programs delivered to mothers alone. The trial comprises five arms: (1) mothers' groups receiving a nutrition program, (2) mothers' groups receiving a bundled nutrition and parenting program, (3) mothers' and fathers' groups receiving a nutrition program, (4) mothers' and fathers' groups receiving a bundled nutrition and parenting program, and (5) control receiving standard of care health services. The primary outcomes are child dietary diversity and early child development (mental and motor development). Parents with a child under 18 months will be enrolled in peer groups and receive twice monthly intervention by trained community health workers. Data will be collected from mothers, fathers, and children at baseline (pre-intervention), midline, and endline (post-intervention). Discussion: EFFECTS will generate evidence on the effects of bundled nutrition and parenting interventions on child nutrition, growth, and development outcomes; determine the benefits of engaging fathers on child, caregiving, and caregiver outcomes; and investigate common and unique pathways between treatments and child outcomes. Trial registration: ClinicalTrials.gov NCT03759821. Registered on November 30, 2018 [ABSTRACT FROM AUTHOR]

Background Animal embryotoxicity data, and the scarcity of safety data in human pregnancies, have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in lifesaving circumstances. We conducted a meta-analysis of prospective observational studies comparing the risk of miscarriage, stillbirth, and major congenital anomaly (primary outcomes) among first-trimester pregnancies treated with artemisinin derivatives versus quinine or no antimalarial treatment. Methods and findings Electronic databases including Medline, Embase, and Malaria in Pregnancy Library were searched, and investigators contacted. Five studies involving 30,618 pregnancies were included; four from sub-Saharan Africa (n = 6,666 pregnancies, six sites) and one from Thailand (n = 23,952). Antimalarial exposures were ascertained by self-report or active detection and confirmed by prescriptions, clinic cards, and outpatient registers. Cox proportional hazards models, accounting for time under observation and gestational age at enrollment, were used to calculate hazard ratios. Individual participant data (IPD) meta-analysis was used to combine the African studies, and the results were then combined with those from Thailand using aggregated data meta-analysis with a random effects model. There was no difference in the risk of miscarriage associated with the use of artemisinins anytime during the first trimester (n = 37/671) compared with quinine (n = 96/945; adjusted hazard ratio [aHR] = 0.73 [95% CI 0.44, 1.21], I.sup.2 = 0%, p = 0.228), in the risk of stillbirth (artemisinins, n = 10/654; quinine, n = 11/615; aHR = 0.29 [95% CI 0.08-1.02], p = 0.053), or in the risk of miscarriage and stillbirth combined (pregnancy loss) (aHR = 0.58 [95% CI 0.36-1.02], p = 0.099). The corresponding risks of miscarriage, stillbirth, and pregnancy loss in a sensitivity analysis restricted to artemisinin exposures during the embryo sensitive period (6-12 wk gestation) were as follows: aHR = 1.04 (95% CI 0.54-2.01), I.sup.2 = 0%, p = 0.910; aHR = 0.73 (95% CI 0.26-2.06), p = 0.551; and aHR = 0.98 (95% CI 0.52-2.04), p = 0.603. The prevalence of major congenital anomalies was similar for first-trimester artemisinin (1.5% [95% CI 0.6%-3.5%]) and quinine exposures (1.2% [95% CI 0.6%-2.4%]). Key limitations of the study include the inability to control for confounding by indication in the African studies, the paucity of data on potential confounders, the limited statistical power to detect differences in congenital anomalies, and the lack of assessment of cardiovascular defects in newborns. Conclusions Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or stillbirth. While the data are limited, they indicate no difference in the prevalence of major congenital anomalies between treatment groups. The benefits of 3-d artemisinin combination therapy regimens to treat malaria in early pregnancy are likely to outweigh the adverse outcomes of partially treated malaria, which can occur with oral quinine because of the known poor adherence to 7-d regimens. Review registration PROSPERO CRD42015032371, Author(s): Stephanie Dellicour 1,*, Esperança Sevene 2,3, Rose McGready 4,5, Halidou Tinto 6, Dominic Mosha 7, Christine Manyando 8, Stephen Rulisa 9, Meghna Desai 10, Peter Ouma 11, Martina Oneko [...]