Concordance of three alternative gestational age assessments for pregnant women from four African countries: A secondary analysis of the MIPPAD trial

Background: At times, ultrasound is not readily available in low resource countries in Africa for accurate determination of gestational age, so using alternative methods is pivotal during pregnancy. These assessments are used to aid the risk analysis for an infant and management strategies for premature delivery, if necessary. Currently, date of last menstrual period, fundal height measurements, and the New Ballard Score are commonly used in resource-limited settings. However, concordance of these measures is unknown for sub-Saharan Africa. We obtained data from an open-label randomized controlled trial, to assess the concordance of these alternative assessment methods. The purpose of our study was to determine the agreement between these alternative methods when used in sub-Saharan African populations. Methods: A total of 4,390 pregnant women from Benin, Gabon, Mozambique and Tanzania were included in our analysis. The assessment methods compared were: 1) reported last menstrual period, 2) symphysis-fundal height measurement, and 3) the New Ballard Score. The Bland-Altman method and intraclass correlation coefficient (ICC) were used to test the degree of agreement. Survival range gestational age, used as an inclusion criterion for further analysis, was from 22 to 44 weeks. Findings: Plots showed a lack of agreement between methods and the 95% limits of agreement too wide to be clinically useful. ICC = 0.25 indicated poor agreement. A post-hoc analysis, restricted from 32 to 42 weeks, was done to check for better agreement in this near-term population. The plots and ICC = 0.16 still confirmed poor agreement.

Using maternal and neonatal data collection systems for coronavirus disease 2019 (COVID-19) vaccines active safety surveillance in low- and middle-income countries: an international modified Delphi study.

Background: Given that pregnant women are now included among those for receipt coronavirus disease 2019 (COVID-19) vaccines, it is important to ensure that information systems can be used (or available) for active safety surveillance, especially in low- and middle-income countries (LMICs). The aim of this study was to build consensus about the use of existing maternal and neonatal data collection systems in LMICs for COVID-19 vaccines active safety surveillance, a basic set of variables, and the suitability and feasibility of including pregnant women and LMIC research networks in COVID-19 vaccines pre-licensure activities. Methods: A three-stage modified Delphi study was conducted over three months in 2020. An international multidisciplinary panel of 16 experts participated. Ratings distributions and consensus were assessed, and ratings' rationale was analyzed. Results: The panel recommended using maternal and neonatal data collection systems for active safety surveillance in LMICs (median 9; disagreement index [DI] -0.92), but there was no consensus (median 6; DI 1.79) on the feasibility of adapting these systems. A basic set of 14 maternal, neonatal, and vaccination-related variables. Out of 16 experts, 11 supported a basic set of 14 maternal, neonatal, and vaccination-related variables for active safety surveillance. Seven experts agreed on a broader set of 26 variables. The inclusion of pregnant women for COVID-19 vaccines research (median 8; DI -0.61) was found appropriate, although there was uncertainty on its feasibility in terms of decision-makers' acceptability (median 7; DI 10.00) and regulatory requirements (median 6; DI 0.51). There was no consensus (median 6; DI 2.35) on the feasibility of including research networks in LMICs for conducting clinical trials amongst pregnant women. Conclusions: Although there was some uncertainty regarding feasibility, experts recommended using maternal and neonatal data collection systems and agreed on a common set of variables for COVID-19 vaccines active safety surveillance in LMICs.

HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique

Background: Few data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care. Objectives: To describe the frequency and characteristics of HIV drug resistance mutations (HIVDRM) in pregnant women with virological failure at delivery, despite pMTCT or antiretroviral therapy (ART). Methods: Samples from HIV-infected pregnant women from a rural area in southern Mozambique were analysed. Only women with HIV-1 RNA >400c/mL at delivery were included in the analysis. HIVDRM were determined using MiSeq® (detection threshold 1%) at the first antenatal care (ANC) visit and at the time of delivery. Results: Ninety and 60 samples were available at the first ANC visit and delivery, respectively. At first ANC, 97% of the women had HIV-1 RNA>400c/mL, 39% had CD4+ counts <350 c/mm3 and 30% were previously not on ART. Thirteen women (14%) had at least one HIVDRM of whom 70% were not on previous ART. Eight women (13%) had at least one HIVDRM at delivery. Out of 37 women with data available from the two time points, 8 (21%) developed at least one new HIVDRM during pMTCT or ART. Twenty seven per cent (53/191), 32% (44/138) and 100% (5/5) of the mutations that were present at enrolment, delivery and that emerged during pregnancy, respectively, were minority mutations (frequency <20%). Conclusions: Even with ultrasensitive HIV-1 genotyping, less than 20% of women with detectable viremia at delivery had HIVDRM before initiating pMTCT or ART. This suggests that factors other than pre-existing resistance, such as lack of adherence or interruptions of the ANC chain, are also relevant to explain lack of virological suppression at the time of delivery in women receiving antiretrovirals drugs during pregnancy.

Infant mortality and morbidity associated with preterm and small-for-gestational-age births in southern Mozambique: A retrospective cohort study

Background: Preterm and small for gestational age (SGA) births have been associated with adverse outcomes during the first stages of life. We evaluated the morbidity and mortality associated with preterm and SGA births during the first year of life in a rural area of Southern Mozambique. Methods: This is a retrospective cohort study using previously collected data from children born at the Manhiça District Hospital in two different periods (2003-2005 and 2010-2012). Newborns were classified as being preterm and/or SGA or as babies not fulfilling any of the previous conditions (term non-SGA). All children were followed up for a year for morbidity and mortality outcomes. Results: A total of 5574 live babies were included in the analysis. The prevalence of preterm delivery was 6.2% (345/5574); the prevalence of SGA was 14.0% (776/5542) and 2.2% (114/5542) of the children presented both conditions. During the neonatal period, preterm delivery and SGA were associated with 13 (HR: 13.0, 95% CI 4.0-42.2) and 5 times (HR: 4.5, 95% CI: 1.6-12.6) higher mortality compared to term non-SGA babies. Risk of hospitalization was only increased when both conditions were present (IRR: 3.5, 95%CI: 1.5-8.1). Mortality is also increased during the entire first year, although at a lower rate. Conclusions: Neonatal and infant mortality rates are remarkably high among preterm and SGA babies in southern Mozambique. These increased rates are concentrated within the neonatal period. Prompt identification of these conditions is needed to implement interventions aimed at increasing survival of these high-risk newborns.

The Safety of Artemisinin Derivatives for the Treatment of Malaria in the 2nd or 3rd Trimester of Pregnancy: A Systematic Review and Meta-Analysis

Given the high morbidity for mother and fetus associated with malaria in pregnancy, safe and efficacious drugs are needed for treatment. Artemisinin derivatives are the most effective antimalarials, but are associated with teratogenic and embryotoxic effects in animal models when used in early pregnancy. However, several organ systems are still under development later in pregnancy. We conducted a systematic review and meta-analysis of the occurrence of adverse pregnancy outcomes among women treated with artemisinins monotherapy or as artemisinin-based combination therapy during the 2nd or 3rd trimesters relative to pregnant women who received non-artemisinin antimalarials or none at all. Pooled odds ratio (POR) were calculated using Mantel-Haenszel fixed effects model with a 0.5 continuity correction for zero events. Eligible studies were identified through Medline, Embase, and the Malaria in Pregnancy Consortium Library. Twenty studies (11 cohort studies and 9 randomized controlled trials) contributed to the analysis, with 3,707 women receiving an artemisinin, 1,951 a non-artemisinin antimalarial, and 13,714 no antimalarial. The PORs (95% confidence interval (CI)) for stillbirth, fetal loss, and congenital anomalies when comparing artemisinin versus quinine were 0.49 (95% CI 0.24-0.97, I2 = 0%, 3 studies); 0.58 (95% CI 0.31-1.16, I2 = 0%, 6 studies); and 1.00 (95% CI 0.27-3.75, I2 = 0%, 3 studies), respectively. The PORs comparing artemisinin users to pregnant women who received no antimalarial were 1.13 (95% CI 0.77-1.66, I2 = 86.7%, 3 studies); 1.10 (95% CI 0.79-1.54, I2 = 0%, 4 studies); and 0.79 (95% CI 0.37-1.67, I2 = 0%, 3 studies) for miscarriage, stillbirth and congenital anomalies respectively. Treatment with artemisinin in 2nd and 3rd trimester was not associated with increased risks of congenital malformations or miscarriage and may be was associated with a reduced risk of stillbirths compared to quinine. This study updates the reviews conducted by the WHO in 2002 and 2006 and supports the current WHO malaria treatment guidelines malaria in pregnancy.

Perceptions of malaria in pregnancy and acceptability of preventive interventions among Mozambican pregnant women: implications for effectiveness of malaria control in pregnancy

Background: Intermittent Preventive Treatment (IPTp) and insecticide treated nets (ITNs) are recommended malaria in pregnancy preventive interventions in sub-Saharan Africa. Despite their cost-effectiveness and seemingly straight-forward delivery mechanism, their uptake remains low. We aimed at describing perceptions of pregnant women regarding malaria and the recommended prevention interventions to understand barriers to uptake and help to improve their effectiveness. Methods and findings: We used mixed methods to collect data among 85 pregnant women from a rural area of Southern Mozambique. Information was obtained through observations, in-depth interviews, and focused ethnographic exercises (Free-listing and Pairwise comparisons). Thematic analysis was performed on qualitative data. Data from focused ethnographic exercises were summarized into frequency distribution tables and matrices. Malaria was not viewed as a threat to pregnancy. Participants were not fully aware of malaria- associated adverse maternal and birth outcomes. ITNs were the most preferred and used malaria preventive intervention, while IPTp fell between second and third. Indoor Residual Spraying (IRS) was the least preferred intervention. Conclusions: Low awareness of the risks and adverse consequences of malaria in pregnancy did not seem to affect acceptability or uptake to the different malaria preventive interventions in the same manner. Perceived convenience, the delivery approach, and type of provider were the key factors. Pregnant women, through antenatal care (ANC) services, can be the vehicles of ITN distribution in the communities to maximise overall ITN coverage. There is a need to improve knowledge about neonatal health and malaria to improve uptake of interventions delivered through channels other than the health facility.