Moo Kho Paw

Chloroquine prophylaxis against vivax malaria in pregnancy: a randomized, double‐blind, placebo‐controlled trial

Objective  To assess the safety of chloroquine (CQ) as prophylaxis against Plasmodium vivax infection during pregnancy.

Safety of artemisinins in first trimester of prospectively followed pregnancies: an observational study

Summary Background Artemisinins, the most effective antimalarials available, are not recommended for falciparum malaria during the first trimester of pregnancy because of safety concerns. Therefore, quinine is used despite its poor effectiveness. Assessing artemisinin safety requires weighing the risks of malaria and its treatment. We aimed to assess the effect of first-trimester malaria and artemisinin treatment on miscarriage and major congenital malformations. Methods In this observational study, we assessed data from antenatal clinics on the Thai–Myanmar border between Jan 1, 1994, and Dec 31, 2013. We included women who presented to antenatal clinics during their first trimester with a viable fetus. Women were screened for malaria, and data on malaria, antimalarial treatment, and birth outcomes were collected. The relationship between artemisinin treatments (artesunate, dihydroartemisinin, or artemether) and miscarriage or malformation was assessed using Cox regression with left-truncation and time-varying exposures. Findings Of 55 636 pregnancies registered between 1994 and 2013, 25 485 pregnancies were analysed for first-trimester malaria and miscarriage, in which 2558 (10%) had first-trimester malaria. The hazard of miscarriage increased 1·61-fold after an initial first-trimester falciparum episode (95% CI 1·32–1·97; p<0·0001), 3·24-fold following falciparum recurrence (2·24–4·68; p<0·0001), and 2·44-fold (1·01–5·88; p=0·0473) following recurrent symptomatic vivax malaria. No difference was noted in miscarriage in first-line falciparum treatments with artemisinin (n=183) versus quinine (n=842; HR 0·78 [95% CI 0·45–1·34]; p=0·3645) or in risk of major congenital malformations (two [2%] of 109 [95% CI 0·22–6·47] versus eight (1%) of 641 [0·54–2·44], respectively). Interpretation First-trimester falciparum and vivax malaria both increase the risk of miscarriage. We noted no evidence of an increased risk of miscarriage or of major congenital malformations associated with first-line treatment with an artemisinin derivative compared with quinine. In view of the low efficacy of quinine and wide availability of highly effective artemisinin-based combination therapies, it is time to reconsider first-trimester antimalarial treatment recommendations. Funding The Wellcome Trust and The Bill & Melinda Gates Foundation.

Estimating Gestational Age in Late Presenters to Antenatal Care in a Resource-Limited Setting on the Thai-Myanmar Border.

Estimating gestational age in resource-limited settings is prone to considerable inaccuracy because crown-rump length measured by ultrasound before 14 weeks gestation, the recommended method for estimating gestational age, is often unavailable. Judgements regarding provision of appropriate obstetric and neonatal care are dependent on accurate estimation of gestational age. We determined the accuracy of the Dubowitz Gestational Age Assessment, a population-specific symphysis-fundal height formula, and ultrasound biometry performed between 16 and 40 weeks gestation in estimating gestational age using pre-existing data from antenatal clinics of the Shoklo Malaria Research Unit on the Thai-Myanmar border, where malaria is endemic. Two cohorts of women who gave birth to live singletons were analysed: 1) 250 women who attended antenatal care between July 2001 and May 2006 and had both ultrasound crown-rump length (reference) and a Dubowitz Gestational Age Assessment; 2) 975 women attending antenatal care between April 2007 and October 2010 who had ultrasound crown-rump length, symphysis-fundal measurements, and an additional study ultrasound (biparietal diameter and head circumference) randomly scheduled between 16 and 40 weeks gestation. Mean difference in estimated newborn gestational age between methods and 95% limits of agreement (LOA) were determined from linear mixed-effects models. The Dubowitz method and the symphysis-fundal height formula performed well in term newborns, but overestimated gestational age of preterms by 2.57 weeks (95% LOA: 0.49, 4.65) and 3.94 weeks (95% LOA: 2.50, 5.38), respectively. Biparietal diameter overestimated gestational age by 0.83 weeks (95% LOA: -0.93, 2.58). Head circumference underestimated gestational age by 0.39 weeks (95% LOA: -2.60, 1.82), especially if measured after 24 weeks gestation. The results of this study can be used to quantify biases associated with alternative methods for estimating gestational age in the absence of ultrasound crown-rump length to inform critical clinical judgements in this population, and as a point of reference elsewhere.

High initiation and long duration of breastfeeding despite absence of early skin-to-skin contact in Karen refugees on the Thai-Myanmar border: a mixed methods study

BackgroundEarly skin-to-skin contact (SSC) after birth is recommended as part of the United Nations Children’s Fund (UNICEF) baby friendly health initiative to promote optimum breastfeeding. This paper reports rates of breastfeeding initiation and duration in a low resource environment, where early SSC is not practised, and explores views of pregnant women and midwives surrounding breastfeeding and swaddling.MethodsData from records from a single hospital on the Thai-Myanmar border where refugee women gave birth during a one-year period (2010) were used to determine breastfeeding initiation rates and the time of the first breastfeed, and duration of breastfeeding of the previous alive child in multigravidae. Focus group discussions (FGD) were conducted to obtain information from pregnant women attending antenatal care about their intended or previous duration of breastfeeding and views on breastfeeding. Interviews with local midwives explored reasons for high rates of breastfeeding in this setting and the practice of newborn swaddling.ResultsOf 1404 live births in 2010 in Maela refugee camp there were 982 evaluable mother-newborn pairs, including 80 infants born before 37 weeks gestation. Initiation of breastfeeding within the first hour after birth and exclusive breastfeeding at discharge in term mother-newborn pairs was 91.2% (823/902) and 99.3% (896/902); and before 37 weeks gestation, 48.8% (39/80) and 98.8% (79/80). Reported duration of previous breastfeeding was 19 (range 2 to 72) months.During FGD all primigravidae (n = 17) intended to breastfeed and all multigravidae (n = 33) had previously breastfed; expected or previous duration of feeding was for more than one year or longer. The major theme identified during FGD was breastfeeding is “good”. Women stated their intention to breastfeed with certainty. This certainty was echoed during the interviews with midwifery staff. SSC requires a delay in early swaddling that in Karen people, with animistic beliefs, could risk loss of the spirit of the newborn or attract malevolent spirits.ConclusionsIn a population with a strong culture of breastfeeding and robust breastfeeding practices, high rates of initiation and duration of breastfeeding were found despite a lack of early skin-to-skin contact. Local preferences, traditions and practices that protect, support and maintain high rates of breastfeeding should be promoted.

Quantifying Low Birth Weight, Preterm Birth and Small-for-Gestational-Age Effects of Malaria in Pregnancy: A Population Cohort Study

Background The association between malaria during pregnancy and low birth weight (LBW) is well described. This manuscript aims to quantify the relative contribution of malaria to small-for-gestational-age (SGA) infants and preterm birth (PTB) in pregnancies accurately dated by ultrasound on the Thai-Myanmar border at the Shoklo Malaria Research Unit. Methods and Findings From 2001 to 2010 in a population cohort of prospectively followed pregnancies, we analyzed all singleton newborns who were live born, normal, weighed in the first hour of life and with a gestational age (GA) between 28+0 and 41+6 weeks. Fractional polynomial regression was used to determine the mean birthweight and standard deviation as functions of GA. Risk differences and factors of LBW and SGA were studied across the range of GA for malaria and non-malaria pregnancies. From 10,264 newborns records, population centiles were created. Women were screened for malaria by microscopy a median of 22 [range 1–38] times and it was detected and treated in 12.6% (1,292) of pregnancies. Malaria was associated with LBW, PTB, and SGA compared to those without malaria. Nearly two-thirds of PTB were classified as LBW (68% (539/789)), most of which 83% (447/539) were not SGA. After GA 39 weeks, 5% (298/5,966) of non-LBW births were identified as SGA. Low body mass index, primigravida, hypertension, smoking and female sex of the newborn were also significantly and independently associated with LBW and SGA consistent with previous publications. Conclusions Treated malaria in pregnancy was associated with an increased risk for LBW, PTB, and SGA, of which the latter are most important for infant survival. Using LBW as an endpoint without adjusting for GA incorrectly estimated the effects of malaria in pregnancy. Ultrasound should be used for dating pregnancies and birth weights should be expressed as a function (or adjusted for GA) of GA in future malaria in pregnancy studies.

Mediation of the effect of malaria in pregnancy on stillbirth and neonatal death in an area of low transmission: observational data analysis

BackgroundMalaria in pregnancy is preventable and contributes significantly to the estimated 5.5 million stillbirths and neonatal deaths that occur annually. The contribution of malaria in pregnancy in areas of low transmission has not been quantified, and the roles of maternal anaemia, small-for-gestational-age status, and preterm birth in mediating the effect of malaria in pregnancy on stillbirth and neonatal death are poorly elucidated.MethodsWe analysed observational data routinely collected at antenatal clinics on the Thai-Myanmar border (1986–2015). We used Cox regression and sequential mediation analysis to determine the effect of falciparum and vivax malaria in pregnancy on antepartum (death in utero) and intrapartum (death during labour) stillbirth and neonatal mortality as well as mediation through maternal anaemia, preterm birth, and small-for-gestational-age status.ResultsOf 61,836 women, 9350 (15%) had malaria in pregnancy, and 526 (0.8%) had stillbirths. In a sub-set of 9090 live born singletons followed from birth there were 153 (1.7%) neonatal deaths. The hazard of antepartum stillbirth increased 2.24-fold [95% confidence interval: 1.47, 3.41] following falciparum malaria (42% mediated through small-for-gestational-age status and anaemia), driven by symptomatic falciparum malaria (hazard ratio, HR: 2.99 [1.83, 4.89]) rather than asymptomatic falciparum malaria (HR: 1.35 [0.61, 2.96]). The hazard of antepartum stillbirth increased 2.21-fold [1.12, 4.33] following symptomatic vivax malaria (24% mediated through small-for-gestational-age status and anaemia) but not asymptomatic vivax malaria (HR: 0.54 [0.20, 1.45]). There was no association between falciparum or vivax malaria in pregnancy and intrapartum stillbirth (falciparum HR: 1.03 [0.58, 1.83]; vivax HR: 1.18 [0.66, 2.11]). Falciparum and vivax malaria in pregnancy increased the hazard of neonatal death 2.55-fold [1.54, 4.22] and 1.98-fold [1.10, 3.57], respectively (40% and 50%, respectively, mediated through small-for-gestational-age status and preterm birth).ConclusionsPrevention of malaria in pregnancy, new and existing interventions to prevent small-for-gestational-age status and maternal anaemia, and improved capacity for managing preterm and small-for-gestational-age newborns will reduce the number of malaria-associated stillbirths and neonatal deaths in malaria-endemic areas.

Is areca innocent? The effect of areca (betel) nut chewing in a population of pregnant women on the Thai-Myanmar border

Eight manuscripts have specifically examined the effects of areca (betel) nut use in pregnant women, seven of which have documented adverse effects on birth weight, newborn neurological status, gender ratio and pregnancy outcomes such as anaemia and miscarriage following areca nut use during pregnancy. A retrospective cohort analysis of migrant and refugee pregnant women attending antenatal clinics along the Thai–Myanmar border (July 1997 to November 2006) was conducted to examine the adverse effects of areca nut use routinely recorded on enrolment. Of 7685 women, 2284 (29.7%) never used areca or smoked (cheroots), 2484 (32.3%) only used areca, 438 (5.7%) only smoked cheroots and 2479 (32.3%) used both areca and cheroots. Pieces of ripe areca nut in a leaf with lime, without tobacco, were used particularly among older multigravid women. Adverse pregnancy effects were not observed in areca nut users compared with non-users. Smoking, but not areca nut use, had a dose-related effect on miscarriage. Areca nut use in conjunction with smoking reduced the adverse effects of smoking on birth weight, further supporting a lack of effect of areca nut. Areca (betel) nut-related adverse pregnancy outcomes were not observed in this population, whereas smoking was clearly harmful. Differences from previous reports may result from the amount or types of areca nut, or quid content, consumed between countries. Smoking, but not areca nut, reduction is likely to improve pregnancy outcomes on the Thai–Myanmar border.

Maternal suicide risk among refugees and migrants

for patients in the public sector in 2008 (Table 1). The proportion of womenwhose primary cause of deathwas obstetric hemorrhage who were living with HIV infection has increased between 2005–2007 and 2011–2013 (Table 2). In the latest report [1], the proportion of women who died due to obstetric hemorrhage who had HIV infection was statistically lower than the proportion with HIV in the overall report (45% vs 65%; Pb0.001). However, it was also notably higher than the national HIV seroprevalence of 29% [1]. Importantly, the risk of hemorrhage was higher among women who were receiving HAART than among those not receiving HAART (relative risk 1.61, 95% confidence interval 1.15–2.25 (Table 2)). This increased tendency to bleeding in pregnancy among women with HIV infection is in line with the findings of Chweneyagae et al. [3]. On the basis of data from the report for 2008–2010 [2], they stated that for deaths due to obstetric hemorrhage, the institutional mortality ratios were 38.4 and 17.2 per 100 000 live births among women with and without HIV infection, respectively [3]. Furthermore, Bloch et al. [4] found increased rates of blood transfusions among pregnant women with HIV infection. The current reanalysis of the South African data adds to the body of evidence suggesting that the frequency of hemorrhage among pregnant women with HIV infection is increasing, which could be associated with the use of HAART. Increased bleeding among women with HIV infection could be associated with anemia, HIV-associated thrombocytopenia, or chorioamnionitis. Alternatively some form of coagulopathy or endothelial dysfunction could be the cause, but this needs further investigation.

Pregnant migrant and refugee women's perceptions of mental illness on the Thai-Myanmar border: a qualitative study.

BackgroundMental illness is a significant contributor to the global burden of disease, with prevalence highest in low- and middle-income countries. Rates are high in women of childbearing age, especially during pregnancy and the first year post-partum. Migrant and refugee populations are at risk of developing mental illness due to the multiple stressors associated with migration. The Thai-Myanmar border area is home to large populations of migrants and refugees as a result of long-standing conflict, poverty and unemployment in Myanmar. This study aims to explore perceptions of mental illness among pregnant migrants and refugees and antenatal clinic staff living and working along the Thai-Myanmar border.MethodsThirteen focus group discussions were conducted with pregnant migrants, pregnant refugees and antenatal clinic staff. Focus groups were held in one large refugee camp and two migrant health clinics along the Thai-Myanmar border. Thematic analysis was used to identify and code themes emerging from the data.ResultsA total of 92 pregnant women and 24 antenatal clinic staff participated. Discussions centered around five main themes: symptoms of mental illness; causes of mental illness; suicide; mental illness during pregnancy and the post-partum period; and managing mental illness. Symptoms of mental illness included emotional disturbances, somatic symptoms and socially inappropriate behavior. The main causes were described as current economic and family-related difficulties. Suicide was frequently attributed to shame. Mental illness was thought to be more common during and following pregnancy due to a lack of family support and worries about the future. Talking to family and friends, medication and hospitalization were suggested as means of helping those suffering from mental illness.ConclusionsMental illness was recognized as a concept by the majority of participants and there was a general willingness to discuss various aspects of it. More formal and systematic training including the development of assessment tools in the local languages would enable better ascertainment and treatment of mental illness in this population.

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age. Methods: We conducted a cohort study on newborns at the Shoklo Malaria Research Unit, along the Thai-Myanmar border between January 2015 and May 2016. The FST was performed at birth on the umbilical cord blood by locally-trained staff and quality controlled by specialised technicians at the central laboratory. The FST was repeated after one month of age. Genotyping for common local G6PD mutations was carried out for all discrepant results. Results: FST was performed on 1521 umbilical cord blood samples. Quality control and genotyping revealed 10 misdiagnoses. After quality control, 10.7% of the males (84/786) and 1.2% of the females (9/735) were phenotypically G6PD deficient at birth. The FST repeated at one month of age or later diagnosed 8 additional G6PD deficient infants who were phenotypically normal at birth. Conclusions: This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control. A more conservative interpretation of the FST in male newborns could increase the diagnostic performances. Quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6PD deficiency on umbilical cord blood and should be investigated.