Search

Background: The COVID-19 pandemic disrupted routine health care and antenatal and birth services globally. The Shoklo Malaria Research Unit (SMRU) based at the Thailand-Myanmar border provides cross border antenatal care (ANC) and birth services to marginalised pregnant women. The border between the countries entered lockdown in March 2020 preventing cross-border access for women from Myanmar to Thailand. SMRU adapted by opening a new clinic during the COVID-19 pandemic in Myanmar. This study explored the impact of the COVID-19 pandemic and response on access to ANC and pregnancy outcomes for marginalised pregnant women in the border regions between Thailand and Myanmar., Methods: A retrospective review of medical records of all pregnancies delivered or followed at antenatal clinics of the SMRU from 2017 to the end of 2022. Logistic regression was done to compare the odds of maternal and neonatal outcomes between women who delivered pre-COVID (2017-2019) and women who delivered in the COVID-19 pandemic (2020-2022), grouped by reported country of residence: Thailand or Myanmar., Results: Between 2017 and the end of 2022, there were 13,865 (5,576 resident in Thailand and 8,276 in Myanmar) marginalised pregnant women who followed ANC or gave birth at SMRU clinics. Outcomes of pregnancy were known for 9,748 women with an EGA ≥ 28 weeks. Unknown outcome of pregnancy among women living in Thailand did not increase during the pandemic. However, there was a high (60%) but transient increase in unknown outcome of pregnancy for women with Myanmar residence in March 2020 following border closure and decreasing back to the baseline of 20-30% after establishment of a new clinic. Non-literate women were more likely to have an unknown outcome during the pandemic. There was no statistically significant increase in known stillbirths or maternal deaths during the COVID pandemic in this population but homebirth was over represented in maternal and perinatal mortality., Conclusion: Decreasing barriers to healthcare for marginalised pregnant women on the Thailand-Myanmar border by establishment of a new clinic was possible in response to sudden border closure during the COVID-19 pandemic and most likely preventing an increase in maternal and perinatal mortality., (© 2024. The Author(s).)

Background: Neonatal hyperbilirubinaemia (NH) is a common problem worldwide and is a cause of morbidity and mortality especially in low-resource settings., Methods: A study was carried out at Shoklo Malaria Research Unit (SMRU) clinics along the Thailand-Myanmar border to evaluate a non-invasive test for diagnosis of NH in a low-resource setting. Performance of a transcutaneous bilirubinometer Dräger Jaundice Meter JM-105 was assessed against routine capillary serum bilirubin testing (with BR-501 microbilirubinometer) before phototherapy during neonatal care in the first week of life. Results were analysed by direct agreement and by various bilirubin thresholds used in clinical practice. Total serum bilirubin was also measured in cord blood at birth and tested for prediction of hyperbilirubinaemia requiring phototherapy in the first week of life., Results: Between April 2020 and May 2023, 742 neonates born at SMRU facilities were included in the study. A total of 695 neonates provided one to nine capillary blood samples for analysis of serum bilirubin (total 1244 tests) during the first week of life. Performance of transcutaneous bilirubinometer was assessed in 307 neonates who provided 687 paired transcutaneous capillary blood tests. Bilirubin levels were also measured in 738 cord blood samples. Adjusted values of transcutaneous bilirubinometer showed excellent agreement with capillary serum bilirubin concentration (intraclass correlation coefficient=0.923) and high sensitivity (>98%) at all clinical thresholds analysed across 3 years of sampling and multiple users. Concentrations of bilirubin detected in cord blood were not useful in identifying neonates at risk of hyperbilirubinaemia requiring treatment., Conclusions: The transcutaneous bilirubinometer is a reliable tool to screen neonates and identify those needing confirmatory blood testing. Bilirubin concentrations in cord blood are not predictive of hyperbilirubinaemia in neonates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Current guidelines advise against primaquine treatment for breastfeeding mothers to avoid the potential for haemolysis in infants with G6PD deficiency. To predict the haemolytic risk, the amount of drug received from the breast milk and the resulting infant drug exposure need to be characterised. Here, we develop a pharmacokinetic model to describe the drug concentrations in breastfeeding women using venous, capillary, and breast milk data. A mother-to-infant model is developed to mimic the infant feeding pattern and used to predict their drug exposures. Primaquine and carboxyprimaquine exposures in infants are <1% of the exposure in mothers. Therefore, even in infants with the most severe G6PD deficiency variants, it is highly unlikely that standard doses of primaquine (0.25-1 mg base/kg once daily given to the mother for 1-14 days) would cause significant haemolysis. After the neonatal period, primaquine should not be restricted for breastfeeding women (Clinical Trials Registration: NCT01780753)., (© 2024. The Author(s).)

Background: In low- and middle-income countries twin births have a high risk of complications partly due to barriers to accessing hospital care. This study compares pregnancy outcomes, maternal and neonatal morbidity and mortality of twin to singleton pregnancy in refugee and migrant clinics on the Thai Myanmar border., Methods: A retrospective review of medical records of all singleton and twin pregnancies delivered or followed at antenatal clinics of the Shoklo Malaria Research Unit from 1986 to 2020, with a known outcome and estimated gestational age. Logistic regression was done to compare the odds of maternal and neonatal outcomes between twin and singleton pregnancies., Results: Between 1986 and 2020 this unstable and migratory population had a recorded outcome of pregnancy of 28 weeks or more for 597 twin births and 59,005 singleton births. Twinning rate was low and stable (<9 per 1,000) over 30 years. Three-quarters (446/597) of the twin pregnancies and 96% (56,626/59,005) of singletons birthed vaginally. During pregnancy, a significantly higher proportion of twin pregnancies compared to singleton had pre-eclampsia (7.0% versus 1.7%), gestational hypertension (9.9% versus 3.9%) and eclampsia (1.0% versus 0.2%). The stillbirth rate of twin 1 and twin 2 was higher compared to singletons: twin 1 25 per 1,000 (15/595), twin 2 64 per 1,000 (38/595) and singletons 12 per 1,000 (680/58,781). The estimated odds ratio (95% confidence interval (CI)) for stillbirth of twin 1 and twin 2 compared to singletons was 2.2 (95% CI 1.3-3.6) and 5.8 (95% CI 4.1-8.1); and maternal death 2.0 (0.95-11.4), respectively, As expected most perinatal deaths were 28 to <32 week gestation., Conclusion: In this fragile setting where access to hospital care is difficult, three in four twins birthed vaginally. Twin pregnancies have a higher maternal morbidity and perinatal mortality, especially the second twin, compared to singleton pregnancies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Prins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Improving breastfeeding rates is one of the most cost-effective ways to prevent infant deaths, but most of the world falls far below WHO recommended breastfeeding practices. Confident, informed healthcare workers are an important resource to promote breastfeeding, but healthcare workers are at risk of early breastfeeding cessation themselves. Culture, ethnicity and socio-economic status impact breastfeeding rates with some of the highest and lowest rates in Southeast Asia reported from Thailand. This study explores the relationship between workplace determinants of breastfeeding, personal breastfeeding outcomes for healthcare workers, and the breastfeeding care healthcare workers provide their patients., Methods: This study used a sequential exploratory design guided by a conceptual framework based on social ecological/ecological psychology models. Participants came from four clinical sites in Northern Thailand, from ethnically Burman or Karen communities with high breastfeeding rates, and Thai communities with low breastfeeding rates. In-depth interviews (July 2020-November 2020) were followed by a quantitative survey (November 2020-July 2021) derived from validated questionnaires (Australian Breastfeeding Knowledge and Attitudes Questionnaire and the Workplace Breastfeeding Support Scale) with minor local adaptations., Results: Interviews highlighted the beneficial effects of supportive workplace policies, the importance of physical spaces to facilitate proximity between mothers and infants, and the problem of low milk production. Meeting the WHO recommended practices of exclusive breastfeeding to 6 months or total breastfeeding to 2 years or more was more common in sites with higher levels of breastfeeding support (aOR 7.3, 95%CI 1.8, 29.1 for exclusive breastfeeding). Exclusive breastfeeding was also higher when staff set breastfeeding goals (aOR 4.4, 95%CI 1.7, 11.5). Staff who were able to see their infants during the work day were less likely to terminate breastfeeding because of work (aOR 0.3, 95%CI 0.1, 0.8). Staff who met both WHO recommendations themselves were more likely to report high levels of confidence caring for breastfeeding patients (aOR 2.6, 95%CI 1.1, 6.4)., Conclusions: Workplace protections including supportive maternity leave policies and child-friendly spaces can improve breastfeeding outcomes for healthcare workers. These improved outcomes are then passed on to patients who benefit from healthcare workers who are more confident and attentive to breastfeeding problems., (© 2024. The Author(s).)

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency represents a barrier to the full deployment of anti-malarial drugs for vivax malaria elimination and of first-line antibiotics. Lack of established reference ranges for G6PD activity in breast-fed infants puts them at risk of drug-induced haemolysis and restricts access to safe treatment of their mothers., Methods: The present work was undertaken to establish age-specific G6PD normal values using the gold standard spectrophotometric assay to support the future clinical use of tafenoquine in lactating women and safer antibiotic treatment in infants., Results: Spectrophotometric results collected at the Thai-Myanmar border from 78 healthy infants between the ages of 2 and 6 months showed a trend of decreased enzymatic activity with increasing age (which did not reach statistical significance when comparing 2-3 months old against 4-6 months old infants) and provided a reference normal value of 100% activity for infants 2-6 months old of 10.18IU/gHb., Conclusions: Normal reference G6PD activity in 2-6-month-old infants was approximately 140% of that observed in G6PD normal adults from the same population. Age specific G6PD activity thresholds should be used in paediatric populations to avoid drug-induced haemolysis., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Bancone G et al.)

Background: Gestational diabetes mellitus (GDM) contributes to maternal and neonatal morbidity. As data from marginalized populations remains scarce, this study compares risk-factor-based to universal GDM screening in a low resource setting. Methods: This is a secondary analysis of data from a prospective preterm birth cohort. Pregnant women were enrolled in the first trimester and completed a 75g oral glucose tolerance test (OGTT) at 24-32 weeks' gestation. To define GDM cases, Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO trial) criteria were used. All GDM positive cases were treated. Sensitivity and specificity of risk-factor-based selection for screening (criteria: age ≥30y, obesity (Body mass index (BMI) ≥27.5kg/m 2 ), previous GDM, 1 st degree relative with diabetes, previous macrosomia (≥4kg), previous stillbirth, or symphysis-fundal height ≥90th percentile) was compared to universal screening using the OGTT as the gold standard. Adverse maternal and neonatal outcomes were compared by GDM status. Results: GDM prevalence was 13.4% (50/374) (95% CI: 10.3-17.2). Three quarters of women had at least one risk factor (n=271 women), with 37/50 OGTT positive cases correctly identified: sensitivity 74.0% (59.7-85.4) and specificity 27.8% (3.0-33.0). Burman women (self-identified) accounted for 29.1% of the cohort population, but 38.0% of GDM cases. Percentiles for birthweight (p=0.004), head circumference (p=0.002), and weight-length ratio (p=0.030) were higher in newborns of GDM positive compared with non-GDM mothers. 21.7% (75/346) of newborns in the cohort were small-for-gestational age (≤10 th percentile). In Burman women, overweight/obese BMI was associated with a significantly increased adjusted odds ratio 5.03 (95% CI: 1.43-17.64) for GDM compared with normal weight, whereas in Karen women, the trend in association was similar but not significant (OR 2.36; 95% CI 0.95-5.89). Conclusions: Risk-factor-based screening missed one in four GDM positive women. Considering the benefits of early detection of GDM and the limited additional cost of universal screening, a two-step screening program was implemented., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Prüst JT et al.)

Background: Hepatitis B causes significant disease and death globally, despite the availability of effective vaccination. Migration likewise affects hundreds of millions of people annually, many of whom are women and children, and increases risks for poor vaccine completion and mother to child transmission of hepatitis B. In the neighbouring countries of Thailand and Myanmar, vaccine campaigns have made progress but little is known about the reach of these programs into migrant worker communities from Myanmar living in Thailand., Methods: A cohort of 253 postpartum women (53 urban migrants in Chiang Mai and 200 rural migrants in Tak Province) were surveyed about their Hepatitis B knowledge and willingness to vaccinate their children between September 10, 2019 and March 30, 2019. They were subsequently followed to determine vaccine completion. When records of vaccination were unavailable at the birth facility, or visits were late, families were contacted and interviewed about vaccination elsewhere, and reasons for late or missed vaccines., Results: Though women in Tak province displayed better knowledge of Hepatitis B and equal intention to vaccinate, they were 14 times less likely to complete Hepatitis B vaccination for their children compared to migrants in Chiang Mai. Tak women were largely undocumented, had private (non-profit) insurance and had more transient residence. In Chiang Mai migrant women were mostly documented and had full access to the Thai national health services. Though minor individual and facility-level differences may have contributed, the major driver of the disparity seems to be the place of migrants within local socio-political-economic systems. The COVID-19 pandemic further disproportionately affected Tak province migrants who faced severe travel restrictions hampering vaccination. Sixty percent of families who were lost to vaccine follow-up in Tak province could not be contacted by phone or home visit. Chiang Mai migrants, with 86.8% vaccine completion, nearly reached the target of 90%., Conclusions: Achievement of high levels of hepatitis B vaccination in migrant communities is important and feasible, and requires inclusive policies that integrate migrants into national health and social services. This is more urgent than ever during the COVID-19 era., (© 2022. The Author(s).)

Background: Suicide is a leading cause of maternal death globally. Migrant and refugee populations may experience higher risk of suicide. We report data on suicidal ideation from migrant and refugee women living on the Thailand-Myanmar border., Methods: Women were recruited in their first trimester of pregnancy. Depression status was assessed by diagnostic interview in the first, second and third trimesters and at 1 month post-partum. We calculated prevalence of suicidal ideation and used logistic regression to identify associated socio-demographic factors., Results: During the perinatal period, 5.3% (30/568) women experienced suicidal ideation. Refugee women were more likely to experience suicidal ideation than migrant women (8.0 versus 3.1%; P = 0.01). Most women with suicidal ideation did not have severe depression. Previous trauma (OR 2.32; 95% CI: 1.70-3.15) and unplanned pregnancy (OR 2.74; 95% CI: 1.10-6.86) were significantly associated with suicidal ideation after controlling for all other variables., Conclusions: Suicidal ideation represents an important symptom among migrant and refugee women on the Thailand-Myanmar border. Screening only those with severe depression may be insufficient to identify women at risk of suicide. Community-level interventions addressing social and gender inequalities and prioritization of family planning programmes are needed alongside targeted suicide prevention initiatives to help lower the rates of people dying by suicide., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health.)

Background: Gestational diabetes mellitus (GDM) contributes significantly to maternal and neonatal morbidity, but data from marginalized populations remains scarce. This study aims to compare risk-factor-based screening to universal testing for GDM among migrants along the Thailand-Myanmar border. Methods: From the prospective cohort (September 2016, February 2019), 374 healthy pregnant women completed a 75g oral glucose tolerance test (OGTT) at 24-32 weeks gestation. Fasting, one hour and two hour cut-offs were based on Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO trial) criteria and cases were treated. The sensitivity and specificity of risk-factor-based screening criteria was calculated using OGTT as the gold standard. Risk factors included at least one positive finding among 10 criteria, e.g., obesity (body mass index (BMI) ≥27.5kg/m 2 ), 1 st degree relative with diabetes etc. Adverse maternal and neonatal outcomes were compared by GDM status, and risk factors for GDM were explored. Results: GDM prevalence was 13.4% (50/374) (95% CI: 10.3-17.2). Risk-factors alone correctly identified 74.0% (37/50) OGTT positive cases: sensitivity 74.0% (59.7-85.4) and specificity 27.8% (3.0-33.0). Burman women accounted for 29.1% of the cohort population, but 38.0% of GDM cases. Percentiles for birthweight (p=0.004), head circumference (p=0.005), and weight-length ratio (p=0.010) were higher in newborns of GDM mothers compared with non-GDM, yet 21.7% (75/346) of newborns in the cohort were small-for-gestational age. In Burman women, overweight/obese BMI was associated with a significantly increased adjusted odds ratio 5.03 (95% CI: 1.43-17.64) for GDM compared to normal weight, whereas underweight and overweight/obese in Karen women were both associated with similarly elevated adjusted odds, approximately 2.4-fold (non-significant) for GDM. GDM diagnosis by OGTT was highest prior to peak rainfall. Conclusions: Risk-factor-based screening was not sufficiently sensitive or specific to be useful to diagnose GDM in this setting among a cohort of low-risk pregnant women. A two-step universal screening program has thus been implemented., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Prüst JT et al.)

Background: Antenatal care and skilled childbirth services are important interventions to improve maternal health and lower the risk of poor pregnancy outcomes and mortality. A growing body of literature has shown that geographic distance to clinics can be a disincentive towards seeking care during pregnancy. On the Thailand-Myanmar border antenatal clinics serving migrant populations have found high rates of loss to follow-up of 17.4%, but decades of civil conflict have made the underlying factors difficult to investigate. Here we perform a comprehensive study examining the geographic, demographic, and health-related factors contributing to loss to follow-up., Methods: Using patient records we conducted a spatial and epidemiological analysis looking for predictors of loss to follow-up and pregnancy outcomes between 2007 and 2015. We used multivariable negative binomial regressions to assess for associations between distance travelled to the clinic and birth outcomes (loss to follow-up, pregnancy complications, and time of first presentation for antenatal care.) RESULTS: We found distance travelled to clinic strongly predicts loss to follow-up, miscarriage, malaria infections in pregnancy, and presentation for antenatal care after the first trimester. People lost to follow-up travelled 50% farther than people who had a normal singleton childbirth (a ratio of distances (DR) 1.5; 95% confidence interval (CI): 1.4 - 1.5). People with pregnancies complicated by miscarriage travelled 20% farther than those who did not have miscarriages (DR: 1.2; CI 1.1-1.3), and those with Plasmodium falciparum malaria in pregnancy travelled 60% farther than those without P. falciparum (DR: 1.6; CI: 1.6 - 1.8). People who delayed antenatal care until the third trimester travelled 50% farther compared to people who attended in the first trimester (DR: 1.5; CI: 1.4 - 1.5)., Conclusions: This analysis provides the first evidence of the complex impact of geography on access to antenatal services and pregnancy outcomes in the rural, remote, and politically complex Thailand-Myanmar border region. These findings can be used to help guide evidence-based interventions to increase uptake of maternal healthcare both in the Thailand-Myanmar region and in other rural, remote, and politically complicated environments., (© 2021. The Author(s).)

This study aimed to explore the internet usage and electronic health literacy (eHL) among adults aged 60 and older with hypertension and to explore the associations between eHL and blood pressure control. A cross-sectional survey was conducted at an out-patient primacy care clinic in the urban city center of Chiang Mai, Thailand. eHL was measured using the eHealth Literacy Scale (eHEALS). Logistic regression was used to identify the association between eHL and blood pressure, adjusting for age and sex as a priori confounders and key sociodemographic factors previously identified in univariable analysis. A total of 110 older adult patients with a history of diagnosed hypertension agreed to participate. The mean age of the participants was 67 years old. Fifty-six participants (50.9%) had used the internet in their lifetime. Among internet users, 37 out of 56 participants (66%) could be classified as having high eHL. However, there was insufficient evidence for associations among internet use, eHL and hypertension control. This result potentially creates new opportunities for eHealth education and interventions. Efforts to produce centralized clear, reliable health information targeting this demographic would be worthwhile to help manage chronic diseases such as hypertension in Thailand in the future.

Background: Short emergency obstetric care (EmOC) courses have demonstrated improved provider confidence, knowledge and skills but impact on indicators such as maternal mortality and stillbirth is less substantial. This manuscript evaluates Advanced Life Support in Obstetrics (ALSO) and Basic Life Support (BLSO) as an adult education tool, in a protracted, post-conflict and resource-limited setting. Methods: A mixed methods evaluation was used. Basic characteristics of ALSO and BLSO participants and their course results were summarized. Kirkpatrick's framework for assessment of education effectiveness included: qualitative data on participants' reactions to training (level 1); and quantitative health indicator data on change in the availability and quality of EmOC and in maternal and/or neonatal health outcomes (level 4), by evaluation of the post-partum haemorrhage (PPH) related maternal mortality ratio (MMR) and stillbirth rate in the eight years prior and following implementation of ALSO and BLSO. Results: 561 Thailand-Myanmar border health workers participated in ALSO (n=355) and BLSO (n=206) courses 2008-2020. Pass rates on skills exceeded 90% for both courses while 50% passed the written ALSO test. Perceived confidence significantly improved for all items assessed. In the eight-year block preceding the implementation of ALSO and BLSO (2000-07) the PPH related MMR per 100,000 live births was 57.0 (95%CI 30.06-108.3)(9/15797) compared to 25.4 (95%CI 11.6-55.4)(6/23620) eight years following (2009-16), p=0.109. After adjustment, PPH related maternal mortality was associated with birth before ALSO/BLSO implementation aOR 3.825 (95%CI 1.1233-11.870), migrant (not refugee) status aOR 3.814 (95%CI 1.241-11.718) and attending ≤four antenatal consultations aOR 3.648 (95%CI 1.189-11.191). Stillbirth rate per 1,000 total births was 18.2 (95%CI 16.2-20.4)(291/16016) before the courses, and 11.1 (95%CI 9.8-12.5)(264/23884) after, p=0.038. Birth before ALSO/ BLSO implementation was associated with stillbirth aoR 1.235 (95%CI 1.018-1.500). Conclusions: This evaluation suggests ALSO and BLSO are sustainable, beneficial, EmOC trainings for adult education in protracted, post-conflict, resource-limited settings., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 McGready R et al.)

Background: Artemisinin and artemisinin-based combination therapy (ACT) partner drug resistance in Plasmodium falciparum have spread across the Greater Mekong Subregion compromising antimalarial treatment. The current 3-day artemether-lumefantrine regimen has been associated with high treatment failure rates in pregnant women. Although ACTs are recommended for treating Plasmodium vivax malaria, no clinical trials in pregnancy have been reported., Methods: Pregnant women with uncomplicated malaria on the Thailand-Myanmar border participated in an open-label randomized controlled trial comparing dihydroartemisinin-piperaquine (DP), artesunate-mefloquine (ASMQ) and a 4-day artemether-lumefantrine regimen (AL + ). The primary endpoint for P. falciparum infections was the PCR-corrected cure rate and for P. vivax infections was recurrent parasitaemia, before delivery or day 63, whichever was longer, assessed by Kaplan-Meier estimate., Results: Between February 2010 and August 2016, 511 pregnant women with malaria (353 P. vivax, 142 P. falciparum, 15 co-infections, 1 Plasmodium malariae) were randomized to either DP (n=170), ASMQ (n=169) or AL + (n=172) treatments. Successful malaria elimination efforts in the region resulted in premature termination of the trial. The majority of women had recurrent malaria (mainly P. vivax relapses, which are not prevented by these treatments). Recurrence-free proportions (95% confidence interval [95% CI]) for vivax malaria were 20.6% (5.1-43.4) for DP (n=125), 46.0% (30.9-60.0) for ASMQ (n=117) and 28.7% (10.0-50.8) for AL +  (n=126). DP and ASMQ provided longer recurrence-free intervals. PCR-corrected cure rates (95% CI) for falciparum malaria were 93.7% (81.6-97.9) for DP (n=49), 79.6% (66.1-88.1) for AMSQ (n=55) and 87.5% (74.3-94.2) for AL + (n=50). Overall 65% (85/130) of P. falciparum infections had Pfkelch13 propeller mutations which increased over time and recrudescence occurred almost exclusively in them; risk ratio 9.42 (95% CI 1.30-68.29). Among the women with falciparum malaria, 24.0% (95% CI 16.8-33.6) had P. vivax parasitaemia within 4 months. Nausea, vomiting, dizziness and sleep disturbance were more frequent with ASMQ. Miscarriage, small-for-gestational-age and preterm birth did not differ significantly among the treatment groups, including first trimester exposures (n=46)., Conclusions: DP was well tolerated and safe, and was the only drug providing satisfactory efficacy for P. falciparum-infected pregnant woman in this area of widespread artemisinin resistance. Vivax malaria recurrences are very common and warrant chloroquine prophylaxis after antimalarial treatment in this area., Trial Registration: ClinicalTrials.gov identifier NCT01054248 , registered on 22 January 2010.

Background: Malaria and hypertensive disorders of pregnancy (HDoP) affect millions of pregnancies worldwide, particularly those of young, first-time mothers. Small case-control studies suggest a positive association between falciparum malaria and risk of pre-eclampsia but large prospective analyses are lacking., Methods: We characterized the relationship between malaria in pregnancy and the development of HDoP in a large, prospectively followed cohort. Pregnant women living along the Thailand-Myanmar border, an area of low seasonal malaria transmission, were followed at antenatal clinics between 1986 and 2016. The relationships between falciparum and vivax malaria during pregnancy and the odds of gestational hypertension, pre-eclampsia, or eclampsia were examined using logistic regression amongst all women and then stratified by gravidity., Results: There were 23,262 singleton pregnancies in women who presented during the first trimester and were followed fortnightly. Falciparum malaria was associated with gestational hypertension amongst multigravidae (adjusted odds ratio (AOR) 2.59, 95%CI 1.59-4.23), whereas amongst primigravidae, it was associated with the combined outcome of pre-eclampsia/eclampsia (AOR 2.61, 95%CI 1.01-6.79). In contrast, there was no association between vivax malaria and HDoP., Conclusions: Falciparum but not vivax malaria during pregnancy is associated with hypertensive disorders of pregnancy.

Quinoline antimalarials cause drug-induced electrocardiographic QT prolongation, a potential risk factor for torsade de pointes. The effects of currently used antimalarials on the electrocardiogram (ECG) were assessed in pregnant women with malaria. Pregnant women with microscopy-confirmed parasitemia of any malaria species were enrolled in an open-label randomized controlled trial on the Thailand-Myanmar border from 2010 to 2016. Patients were randomized to the standard regimen of dihydroartemisinin-piperaquine (DP) or artesunate-mefloquine (ASMQ) or an extended regimen of artemether-lumefantrine (AL+). Recurrent Plasmodium vivax infections were treated with chloroquine. Standard 12-lead electrocardiograms were assessed on day 0, 4 to 6 h following the last dose, and day 7. QT was corrected for the heart rate by a linear mixed-effects model-derived population-based correction formula (QTcP = QT/RR 0.381 ). A total of 86 AL+, 82 ASMQ, 88 DP, and 21 chloroquine-treated episodes were included. No patients had an uncorrected QT interval nor QTcP of >480 ms at any time. QTcP corresponding to peak drug concentration was longer in the DP group (adjusted predicted mean difference, 17.84 ms; 95% confidence interval [CI], 11.58 to 24.10; P  < 0.001) and chloroquine group (18.31 ms; 95% CI, 8.78 to 27.84; P  < 0.001) than in the AL+ group, but not different in the ASMQ group (2.45 ms; 95% CI, -4.20 to 9.10; P  = 0.47) by the multivariable linear mixed-effects model. There was no difference between DP and chloroquine ( P  = 0.91). QTc prolongation resulted mainly from widening of the JT interval. In pregnant women, none of the antimalarial drug treatments exceeded conventional thresholds for an increased risk of torsade de pointes., (Copyright © 2021 Saito et al.)

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.

Background: Soil-transmitted helminth (STH) infections are widespread in tropical and subtropical regions. While many STH infections are asymptomatic, vulnerable populations such as pregnant women face repercussions such as aggravation of maternal anaemia. However, data on prevalence and the effect of STH infections in pregnancy are limited. The aim of this analysis was to describe the burden of STH infections within and between populations of pregnant women from a local refugee camp to a mobile migrant population, and to explore possible associations between STH infection and pregnancy outcomes., Methodology: This is a retrospective review of records from pregnant refugee and migrant women who attended Shoklo Malaria Research Unit antenatal care (ANC) clinics along the Thailand-Myanmar border between July 2013 and December 2017. Inclusion was based on provision of a stool sample during routine antenatal screening. A semi-quantitative formalin concentration method was employed for examination of faecal samples. The associations between STH mono-infections and maternal anaemia and pregnancy outcomes (i.e., miscarriage, stillbirth, preterm birth, and small for gestational age) were estimated using regression analysis., Principal Findings: Overall, 12,742 pregnant women were included, of whom 2,702 (21.2%) had a confirmed infection with either Ascaris lumbricoides, hookworm, Trichuris trichiura, or a combination of these. The occurrence of STH infections in the refugee population (30.8%; 1,246/4,041) was higher than in the migrant population (16.7%; 1,456/8,701). A. lumbricoides was the predominant STH species in refugees and hookworm in migrants. A. lumbricoides and hookworm infection were associated with maternal anaemia at the first ANC consultation with adjusted odds ratios of 1.37 (95% confidence interval (CI) 1.08-1.72) and 1.65 (95% CI 1.19-2.24), respectively. Pregnant women with A. lumbricoides infection were less likely to miscarry when compared to women with negative stool samples (adjusted hazard ratio 0.63, 95% CI 0.48-0.84). STH infections were not significantly associated with stillbirth, preterm birth or being born too small for gestational age. One in five pregnant women in this cohort had STH infection. Association of STH infection with maternal anaemia, in particular in the event of late ANC enrolment, underlines the importance of early detection and treatment of STH infection. A potential protective effect of A. lumbricoides infection on miscarriage needs confirmation in prospective studies., Competing Interests: The authors have declared that no competing interests exist.

Background: Anesthesia in lactating women is frequently indicated for time-sensitive procedures such as postpartum tubal ligation. Ketamine and diazepam are two of the most commonly used anesthetic agents in low resource settings, but their safety profile in lactating women has not been established., Methods: Medical records of post-partum tubal ligations between 2013 and 2018 at clinics of the Shoklo Malaria Research Unit were reviewed for completeness of key outcome variables. Logistic regression identified presence or absence of associations between drug doses and adverse neonatal outcomes: clinically significant weight loss (≥95th percentile) and neonatal hyperbilirubinemia requiring phototherapy., Results: Of 358 records reviewed, 298 were lactating women with singleton, term neonates. There were no severe outcomes in mothers or neonates. On the first postoperative day 98.0% (290/296) of neonates were reported to be breastfeeding well and 6.4% (19/298) had clinically significant weight loss. Phototherapy was required for 13.8% (41/298) of neonates. There was no association between either of the outcomes and increasing ketamine doses (up to 3.8 mg/kg), preoperative oral diazepam (5 mg), or increasing lidocaine doses (up to 200 mg). Preoperative oral diazepam resulted in lower doses of intraoperative anesthetics. Doses of intravenous diazepam above 0.1 mg/kg were associated with increased risk (adjusted odds ratio per 0.1 mg/kg increase, 95%CI) of weight loss (1.95, 95%CI 1.13-3.35, p = 0.016) and jaundice requiring phototherapy (1.87, 95%CI 1.11-3.13, p = 0.017)., Conclusions: In resource-limited settings ketamine use appears safe in lactating women and uninterrupted breastfeeding should be encouraged and supported. Preoperative oral diazepam may help reduce intraoperative anesthetic doses, but intravenous diazepam should be used with caution and avoided in high doses in lactating women.

Introduction: To examine the interactions between short maternal stature, body mass index (BMI) and gestational weight gain (GWG) among appropriate for gestational age (AGA) term newborns in a population of refugees and migrants in Southeast Asia., Methods: This is a retrospective cohort study from 2004 to 2016, including women delivering term, singleton newborns, with first trimester height, weight and gestation dated by ultrasound and a last body weight measured within 4 weeks of birth. AGA newborns were those not classified as small for gestational age or large for gestational age by either INTERGROWTH-21st or Gestation Related Optimal Weight standards. The influence of maternal stature on GWG in delivering an AGA newborn was analysed, with GWG compared with existing National Academy of Medicine (NAM) recommendations., Results: 4340 women delivered AGA newborns. Mean maternal height (SD) was 151.5 cm (5.13), with 58.5% of women considered too short by INTERGROWTH-21st standards. Only one in four women (26.5%, 1150/4340) had GWG within NAM recommendations. Women of shorter stature had a significantly lower mean GWG compared with taller women in underweight and normal BMI categories (p<0.001 for both BMI categories). Mean GWG of overweight and obese women did not differ by height (p=1.0 and p=0.85, respectively) and fell within the lower range of NAM recommendations., Conclusion: These results suggest that short maternal stature can be an important predictor of GWG and should be considered with prepregnancy BMI. Limited-resource settings and special populations need robust GWG recommendations that reflect height and BMI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women., Methods: We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013., Findings: Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57-14·54, p<0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14-0·52, p<0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34-0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18-0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29-23·82)., Interpretation: Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation., Funding: The Bill & Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection., Methods: A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013., Results: Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001)., Conclusions: The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.

Background: The Sustainable Development Goals (SDG) call for increased gender equity and reduction in malaria-related mortality and morbidity. Plasmodium vivax infections in pregnancy are associated with maternal anaemia and increased adverse perinatal outcomes. Providing radical cure for women with 8-aminoquinolines (e.g., primaquine) is hindered by gender-specific complexities., Case Presentation: A symptomatic episode of vivax malaria at 18 weeks of gestation in a primigravid woman was associated with maternal anaemia, a recurrent asymptomatic P. vivax episode, severe intra-uterine growth restriction with no other identifiable cause and induction to reduce the risk of stillbirth. At 5 months postpartum a qualitative glucose-6-phosphate dehydrogenase (G6PD) point-of-care test was normal and radical cure with primaquine was prescribed to the mother. A 33% fractional decrease in haematocrit on day 7 of primaquine led to further testing which showed intermediate phenotypic G6PD activity; the G6PD genotype could not be identified. Her infant daughter was well throughout maternal treatment and found to be heterozygous for Mahidol variant., Conclusion: Adverse effects of vivax malaria in pregnancy, ineligibility of radical cure for pregnant and postpartum women, and difficulties in diagnosing intermediate levels of G6PD activity multiplied morbidity in this woman. Steps towards meeting the SDG include prevention of malaria in pregnancy, reducing unnecessary exclusion of women from radical cure, and accessible quantitative G6PD screening in P. vivax-endemic settings.

Health literacy is increasingly recognized as an important determinant of health outcomes, but definition, measurement tools, and interventions are lacking. Conceptual frameworks must include both individual and health-systems domains which, in combination, determine an individual's health literacy. Validated tools lack applicability in marginalized populations with very low educational levels, such as migrant worker communities on the Myanmar-Thailand border. We undertake a comprehensive health literacy assessment following a case study of a recent public health campaign promoting preconceptual folic acid uptake in this community. A mixed-methods design utilized quantitative analysis of the prevalence and predictors of low Health literacy, and focus group discussions to gather qualitative data from women about proposed and actual posters used in the campaign. Health literacy was measured with a locally developed tool that has been used in surveys of the population since 1995. Health literacy was low, with 194/525 (37.0%) of tested women demonstrating adequate health literacy, despite 63.1% (331/525) self-reporting being literate. Only one third of women had completed 4th grade or above and reported grade level attained in school was more predictive of health literacy than self-reported literacy. Focus group discussions revealed that low literacy, preconceived associations, and traditional health beliefs (individual domain) interacted with complex images, subtle concepts, and taboo images on posters (health-systems domain) to cause widespread misunderstandings of the visuals used in the campaign. The final poster still required explanation for clarity. Low health literacy is prevalent among pregnant women from this migrant community and barriers to communication are significant and complex. Public health posters need piloting prior to implementation as unanticipated misperceptions are common and difficult to overcome. Verbal communication remains a key method of messaging with individuals of low health literacy and educational system strengthening and audiovisual messaging are critical for improvement of health outcomes., Competing Interests: The authors have declared that no competing interests exist.

The objective of the present study is to summarise trends in under- and over-nutrition in pregnant women on the Thailand-Myanmar border. Refugees contributed data from 1986 to 2016 and migrants from 1999 to 2016 for weight at first antenatal consultation. BMI and gestational weight gain (GWG) data were available during 2004-2016 when height was routinely measured. Risk factors for low and high BMI were analysed for &lt;18·5 kg/m2 or ≥23 kg/m2, respectively. A total of 48 062 pregnancies over 30 years were available for weight analysis and 14 646 pregnancies over 13 years (2004-2016) had BMI measured in first trimester (&lt;14 weeks' gestational age). Mean weight at first antenatal consultation in any trimester increased over the 30-year period by 2·0 to 5·2 kg for all women. First trimester BMI has been increasing on average by 0·5 kg/m2 for refugees and 0·6 kg/m2 for migrants, every 5 years. The proportion of women with low BMI in the first trimester decreased from 16·7 to 12·7 % for refugees and 23·1 to 20·2 % for migrants, whereas high BMI increased markedly from 16·9 to 33·2 % for refugees and 12·3 to 28·4 % for migrants. Multivariate analysis demonstrated low BMI as positively associated with being Burman, Muslim, primigravid, having malaria during pregnancy and smoking, and negatively associated with refugee as opposed to migrant status. High BMI was positively associated with being Muslim and literate, and negatively associated with age, primigravida, malaria, anaemia and smoking. Mean GWG was 10·0 (sd 3·4), 9·5 (sd 3·6) and 8·3 (sd 4·3) kg, for low, normal and high WHO BMI categories for Asians, respectively.

Objectives: Hepatitis B virus (HBV) was believed to have minimal impact on pregnancy outcomes apart from the risk of perinatal transmission. In more recent years, there have been reports of adverse associations, most consistently preterm birth (PTB), but this is in the context of high rates of caesarean section. The aim of this study was to explore the association of HBV on pregnancy outcomes in marginalized, low-income populations on the Myanmar-Thailand border., Methods: HBsAg positive (+) point of care rapid detection tests results were confirmed by immunoassays. Women with a confirmed HBsAg status, HIV- and syphilis-negative at first antenatal care screening, singleton fetus and known pregnancy outcome (Aug-2012 to Dec-2016) were included. Logistic regression analysis was used to evaluate associations between HBV group (controls HBsAg negative, HBsAg+/HBeAg-, or HBsAg+/HBeAg+) and pregnancy outcome and comorbidity., Results: Most women were tested, 15,046/15,114 (99.6%) for HBV. The inclusion criteria were not met for 4,089/15,046 (27.2%) women due mainly to unavailability of pregnancy outcome and nonconfirmation of HBsAg+. In evaluable women 687/11,025 (6.2%) were HBsAg+, with 476/11,025 (4.3%) HBsAg+/HBeAg- and 211/11,025 (1.9%) were HBsAg+/HBeAg+. The caesarean section rate was low at 522/8,963 (5.8%). No significant associations were observed between pregnancy comorbidities or adverse pregnancy outcomes and HBV status., Conclusions: The results highlight the disease burden of HBV in women on the Myanmar-Thailand border and support original reports of a lack of significant associations with HBsAg+ irrespective of HBeAg status, for comorbidity, and pregnancy outcomes in deliveries supervised by skilled birth attendants.

Background : Anaemia in pregnancy is typically due to iron deficiency (IDA) but remains a complex and pervasive problem, particularly in low resource settings. At clinics on the Myanmar-Thailand border, a protocol was developed to guide treatment by health workers in antenatal care (ANC). Objective : To evaluate the clinical use of a protocol to treat anaemia in pregnancy. Methods : The design was a descriptive retrospective analysis of antenatal data obtained during the use of a standard anaemia treatment protocol. Two consecutive haematocrits (HCT) <30% prompted a change from routine prophylaxis to treatment doses of haematinics. Endpoints were anaemia at delivery (most recent HCT before delivery <30%) and timeliness of treatment initiation. Women whose HCT failed to respond to the treatment were investigated. Results : From August 2007 to July 2012, a median [IQR] of five [4-11] HCT measurements per woman resulted in the treatment of anaemia in 20.7% (2,246/10,886) of pregnancies. Anaemia at delivery was present in 22.8% (511/2,246) of treated women and 1.4% (123/8,640) who remained on prophylaxis. Human error resulted in a failure to start treatment in 97 anaemic women (4.1%, denominator 2,343 (2,246 + 97)). Fluctuation of HCT around the cut-point of 30% was the major problem with the protocol accounting for half of the cases where treatment was delayed greater than 4 weeks. Delay in treatment was associated with a 1.5 fold higher odds of anaemia at delivery (95% CI 1.18, 1.97). Conclusion : There was high compliance to the protocol by the health workers. An important outcome of this evaluation was that the clinical definition of anaemia was changed to diminish missed opportunities for initiating treatment. Reduction of anaemia in pregnancy requires early ANC attendance, prompt treatment at the first HCT <30%, and support for health workers.

Introduction: Malaria in pregnancy and postpartum cause maternal mortality and adverse fetal outcomes. Efficacious and safe antimalarials are needed to treat and prevent such serious consequences. However, because of the lack of evidence on fetal safety, quinine, an old and less efficacious drug has long been recommended for pregnant women. Uncertainty about safety in relation to breastfeeding leads to withholding of efficacious treatments postpartum or cessation of breastfeeding. Areas covered: A search identified literature on humans in three databases (MEDLINE, Embase and Global health) using pregnancy or lactation, and the names of antimalarial drugs as search terms. Adverse reactions to the mother, fetus or breastfed infant were summarized together with efficacies. Expert opinion: Artemisinins are more efficacious and well-tolerated than quinine in pregnancy. Furthermore, the risks of miscarriage, stillbirth or congenital abnormality were not higher in pregnancies exposed to artemisinin derivatives for treatment of malaria than in pregnancies exposed to quinine or in the comparable background population unexposed to any antimalarials, and this was true for treatment in any trimester. Assessment of safety and efficacy of antimalarials including dose optimization for pregnant women is incomplete. Resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum and long unprotected intervals between intermittent treatment doses begs reconsideration of current preventative recommendations in pregnancy. Data remain limited on antimalarials during breastfeeding; while most first-line drugs appear safe, further research is needed.

Non-communicable diseases (NCDs) are emerging rapidly. This manuscript reports on a pilot survey of NCDs at a primary healthcare level in a marginalised migrant population on the Thailand-Myanmar border in the face of declining rates of malaria. A retrospective audit of routine clinic (2004-2016) and NCD patient survey data (2014-2016) was conducted. The length of follow-up was assessed by Kaplan-Meier analysis. From July 2014 to July 2016, 238 migrant patients were on the NCD register. Hypertension (n = 80) and diabetes mellitus (n = 51) were the most common diagnoses. After the first consultation, 41% (95% confidence interval = 35-47%) were lost to follow-up by 30 days. NCD retention rates were low: 50% of registered patients were lost to follow-up by 80 (95% CI = 49-132) days. After this survey, a novel low-cost insurance scheme for the migrant community has been launched in this area. Development of new schemes involving patients, healthcare providers and funding support are required for improved and sustainable NCD care for marginalised populations.

Background: Primaquine is the only drug providing radical cure of Plasmodium vivax malaria. It is not recommended for breastfeeding women as it causes hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, and breast milk excretion and thus infant exposure are not known., Methods: Healthy G6PD-normal breastfeeding women with previous P. vivax infection and their healthy G6PD-normal infants between 28 days and 2 years old were enrolled. Mothers took primaquine 0.5 mg/kg/day for 14 days. Primaquine and carboxyprimaquine concentrations were measured in maternal venous plasma, capillary plasma, and breast milk samples and infant capillary plasma samples taken on days 0, 3, 7, and 13., Results: In 20 mother-infant pairs, primaquine concentrations were below measurement thresholds in all but 1 infant capillary plasma sample (that contained primaquine 2.6 ng/mL), and carboxyprimaquine was likewise unmeasurable in the majority of infant samples (maximum value 25.8 ng/mL). The estimated primaquine dose received by infants, based on measured breast milk levels, was 2.98 µg/kg/day (ie, ~0.6% of a hypothetical infant daily dose of 0.5 mg/kg). There was no evidence of drug-related hemolysis in the infants. Maternal levels were comparable to levels in nonlactating patients, and adverse events in mothers were mild., Conclusions: The concentrations of primaquine in breast milk are very low and therefore very unlikely to cause adverse effects in the breastfeeding infant. Primaquine should not be withheld from mothers breastfeeding infants or young children. More information is needed in neonates., Clinical Trials Registration: NCT01780753.

Objectives: Preconception folic acid (PFA) taken at least 3 months before conception can decrease the incidence of neural tube defects (NTDs) by approximately 46%. NTDs contribute significantly to neonatal morbidity and mortality in migrant and refugee populations on the Thailand-Myanmar border (incidence 1.57/1000 live births). This audit aimed to assess uptake of PFA among migrant and refugee women, evaluate knowledge about PFA among local healthcare workers and implement a participatory community intervention to increase PFA uptake and decrease NTD incidence in this population., Study Design: A mixed-methods baseline evaluation was followed by an intervention involving health worker education and a community outreach program. A follow-up audit was performed 18 months post-intervention., Methods: Data were gathered via surveys, short interviews and focus group discussions. The intervention program included community-based workshops, production and distribution of printed flyers and posters, and outreach to various local organisations., Results: Uptake of PFA was <2% both before and after the intervention. Despite a substantial increase in local healthcare worker knowledge of PFA, no significant improvement in PFA uptake after the intervention was detected. Most pregnancies in this local community sample were reported to be unplanned., Conclusions: High rates of NTDs with low PFA uptake remains a major public health challenge in this transient population. Results indicate that improved health worker knowledge alone is not sufficient to enhance PFA uptake in this population. Integration of PFA education within expanded family planning programs and broad-based food fortification may be more effective., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Currently there are more adolescents (10-19 years old) and young adults (20-24 years old) than ever. Reproductive health among this age group is often overlooked, although it can have a profound impact on the future. This is especially the case in conflict zones and refugee settings, where there is a heightened need for reproductive health care, and where both the resources and possibility for data collation are usually limited. Methods: Here we report on pregnancies, birth outcomes and risk factors for repeat pregnancies among adolescent and young adult refugees and migrants from antenatal clinics on the Thailand-Myanmar border across a 30 year time span. Results: Pregnancy and fertility rates were persistently high. Compared with 20-24-year-olds, 15-19-year-olds who reported being unable to read had 2.35 (CI: 1.97 - 2.81) times the odds for repeat pregnancy (gravidity >2). In primigravidae, the proportion of small for gestational age (SGA) and preterm births (PTB), and neonatal deaths (NND) decreased with increasing maternal age (all p <0.001). After adjustment, this association retained significance for PTB (cut-off point, ≤18 years) but not for SGA and NND. Conclusions: There is considerable room for improvement in adolescent pregnancy rates in these border populations, and educational opportunities may play a key role in effective interventions., Competing Interests: No competing interests were disclosed.

Background: Under- and over-nutrition during pregnancy are known risk factors for pregnancy complications and adverse pregnancy and infant outcomes. Understanding perceptions around nutrition in pregnancy can create culturally appropriate interventions for improved health outcomes., Objective: A mixed-methods study was performed to explore local perceptions and practices of diet and physical activity in pregnancy in a marginalised population along the Myanmar-Thailand border., Methods: From April to July 2017, a cross-sectional survey and focus group discussions were conducted with pregnant women reporting to antenatal care; in-depth interviews were conducted with senior midwives at participating organisations along the Myanmar-Thailand border., Results: A total of 388 pregnant women were interviewed at two clinic sites along the Myanmar-Thailand border. A high proportion of women had limited knowledge of and poor dietary practices. Consuming a sweetened drink in the last 24 hours as well as being a non-teenage, multigravida woman was significantly associated with high body mass index (BMI) compared to normal BMI. Qualitative analysis combined focus group discussions (n = 66) and in-depth interviews (n = 4) summarising emergent themes: common foods eaten or avoided and rationale; benefits of nutrition; perceptions of overweight and weight gain during pregnancy; barriers to a healthy diet; and sources of diet information., Conclusions: There is limited awareness about healthy diets and lifestyle in these marginalised, migrant communities along the Myanmar-Thailand border. This study suggests that simple, culturally appropriate messaging should be provided to women and communities with low health literacy to generate awareness about healthy lifestyles and their effects on pregnancy outcomes as an important element of a broader strategy to address maternal nutrition in this population. However, more studies to determine the effectiveness of a broad range of interventions in low- and middle-income countries (LMIC) are needed, especially in marginalised migrant populations.

Background: Considering the uncertainty of safety of anti-malarial drugs in pregnancy, efficacy studies are one of the few sources of clinical safety data. Complete safety evaluation is not usually incorporated in efficacy studies due to financial and human resource constraints. This review reports the methods used for the assessment of safety of artemisinin-based and quinine-based treatments in efficacy studies in pregnancy., Methods: Methodology of assessment and reporting of safety in efficacy studies of artemisinin-based and quinine-based treatment in pregnancy was reviewed using seven databases and two clinical trial registries. The protocol was registered to PROSPERO (CRD42017054808)., Results: Of 48 eligible efficacy studies the method of estimation of gestational age was reported in only 32 studies (67%, 32/48) and ultrasound was used in 18 studies (38%, 18/48). Seventeen studies (35%, 17/48) reported parity, 9 (19%, 9/48) reported gravidity and 13 (27%, 13/48) reported both. Thirty-eight studies (79%, 38/48) followed participants through to pregnancy outcome. Fetal loss was assessed in 34 studies (89%, 34/38), but the definition of miscarriage and stillbirth were defined only in 11 (32%, 11/34) and 7 (21%, 7/34) studies, respectively. Preterm birth was assessed in 26 studies (68%, 26/38) but was defined in 16 studies (62%, 16/26). Newborn weight was assessed in 30 studies (79%, 30/38) and length in 10 studies (26%, 10/38). Assessment of birth weight took gestational age into account in four studies (13%, 4/30). Congenital abnormalities were reported in 32 studies (84%, 32/38). Other common risk factors for adverse pregnancy outcomes were not well-reported., Conclusion: Incomplete reporting and varied methodological assessment of pregnancy outcomes in anti-malarial drug efficacy studies limits comparison across studies. A standard list of minimal necessary parameters to assess and report the safety component of efficacy studies of anti-malarials in pregnancy is proposed.

Background: There is no agreed standard method to assess the efficacy of anti-malarials for uncomplicated falciparum in pregnancy despite an increased risk of adverse outcomes for the mother and the fetus. The aim of this review is to present the currently available evidence from both observational and interventional cohort studies on anti-malarial efficacy in pregnancy and summarize the variability of assessment and reporting found in the review process., Methods: Efficacy methodology and assessment of artemisinin-based treatments (ABT) and quinine-based treatments (QBT) were reviewed systematically using seven databases and two clinical trial registries (protocol registration-PROSPERO: CRD42017054808). Pregnant women in all trimesters with parasitologically confirmed uncomplicated falciparum malaria were included irrespective of symptoms. This review attempted to re-calculate proportions of treatment success applying the same definition as the standard WHO methodology for non-pregnant populations. Aggregated data meta-analyses using data from randomized control trials (RCTs) comparing different treatments were performed by random effects model., Results: A total of 48 eligible efficacy studies were identified including 7279 treated Plasmodium falciparum episodes. While polymerase chain reaction (PCR) was used in 24 studies for differentiating recurrence, the assessment and reporting of treatment efficacy was heterogeneous. When the same definition could be applied, PCR-corrected treatment failure of ≥ 10% at any time points was observed in 3/30 ABT and 3/7 QBT arms. Ten RCTs compared different combinations of ABT but there was a maximum of two published RCTs with PCR-corrected outcomes for each comparison. Five RCTs compared ABT and QBT. Overall, the risk of treatment failure was significantly lower in ABT than in QBT (risk ratio 0.22, 95% confidence interval 0.07-0.63), although the actual drug combinations and outcome endpoints were different. First trimester women were included in 12 studies none of which were RCTs of ABT., Conclusions: Efficacy studies in pregnancy are not only limited in number but use varied methodological assessments. In five RCTs with comparable methodology, ABT resulted in higher efficacy than QBT in the second and third trimester of pregnancy. Individual patient data meta-analysis can include data from observational cohort studies and could overcome some of the limitations of the current assessment given the paucity of data in this vulnerable group.

Background : Inherited red blood cell disorders are prevalent in populations living in malaria endemic areas; G6PD deficiency is associated with oxidant-induced haemolysis and abnormal haemoglobin variants may cause chronic anaemia. In pregnant women, microcytic anaemia caused by haemoglobinopathies mimics iron deficiency, complicating diagnosis and treatment. Anaemia during pregnancy is associated with morbidity and mortality. The aim of this study was to characterise the prevalence of G6PD deficiency and haemoglobinopathies  among the pregnant population living along the Thailand-Myanmar border. Pregnant women attending antenatal clinics in this area belong to several distinct ethnic groups. Methods : Data were available for 13,520 women attending antenatal care between July 2012 and September 2016. Screening for G6PD deficiency was done by fluorescent spot test routinely. G6PD genotyping and quantitative phenotyping by spectrophotometry were analysed in a subsample of women. Haemoglobin variants were diagnosed by HPLC or capillary electrophoresis and molecular methods. The prevalence and distribution of inherited red blood cell disorders was analysed with respect to ethnicity. Results : G6PD deficiency was common, especially in the Sgaw Karen ethnic group, in whom the G6PD Mahidol variant allele frequency was 20.7%. Quantitative G6PD phenotyping showed that 60.5% of heterozygous women had an intermediate enzymatic activity between 30% and 70% of the population median. HbE, beta-thalassaemia trait and Hb Constant Spring were found overall in 15.6% of women. Only 45.2% of women with low percentage of HbA 2 were carriers of mutations on the alpha globin genes. Conclusions : Distribution of G6PD and haemoglobin variants varied among the different ethnic groups, but the prevalence was generally high throughout the cohort. These findings encourage the implementation of an extended program of information and genetic counselling to women of reproductive age and will help inform future studies and current clinical management of anaemia in the pregnant population in this region., Competing Interests: No competing interests were disclosed.

Background: Individuals in conflict-affected areas rarely get appropriate care for chronic or non-infectious diseases. The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide, and new evidence shows conclusively that the negative effects of hyperglycemia occur even at mild glucose elevations and that these negative effects can be attenuated by treatment. Scientific literature on gestational diabetes in refugee camp settings is critically limited., Methods: A 75 g 2-hour glucose tolerance test was administered to 228 women attending the antenatal care (ANC) clinic in Maela refugee camp on the Thai-Myanmar border. Prevalence of GDM was determined using the HAPO trial cut-offs [≥92 mg/dL (fasting),≥180 (1 hour), and≥153 (2 hour)] and the WHO criteria [≥126 mg/dL (fasting), and 140 mg/dL (2 hour)]., Results: From July 2011 to March 2012, the prevalence of GDM was 10.1% [95% confidence interval (CI): 6.2-14.0] when the cut-off determined by the HAPO trial was applied. Applying the older WHO criteria yielded a prevalence of 6.6% (95% CI 3.3-9.8). Age, parity, and BMI emerged as characteristics that may be significantly associated with GDM in this population. Other risk factors that are commonly used in screening guidelines were not applicable in this diabetes-naïve population., Discussion: The prevalence of GDM is lower in this population compared with other populations, but still complicates 10% of pregnancies. New evidence regarding gestational diabetes raises new dilemmas for healthcare providers in resource-poor settings. Efforts to identify and treat patients at risk for adverse outcomes need to be balanced with awareness of the risks and burdens associated with over diagnosis and unnecessary interventions. Screening approaches based on risk factors or using higher cut-off values may help minimize this burden and identify those most likely to benefit from intervention.

Background: Current evidence for optimal management of fetal nuchal cord detected after the head has birthed supports techniques that avoid ligation of the umbilical cord circulation. Routine audit found frequent unsafe management of nuchal cord by skilled birth attendants (SBAs) in migrant and refugee birth centres on the Thai-Burmese border., Method: The audit cycle was used to enhance safe practice by SBA for the fetus with nuchal cord. In the three birth centres the action phase of the audit cycle was initially carried out by the doctor responsible for the site. Six months later a registered midwife, present six days per week for three months in one birth facility, encouraged SBAs to facilitate birth with an intact umbilical circulation for nuchal cord. Rates of cord ligation before birth were recorded over a 24 month period (1-July-2011 to 30-June-2013) and in-depth interviews and a knowledge survey of the SBAs took place three months after the registered midwife departure., Results: The proportion of births with nuchal cord ligation declined significantly over the four six monthly quarters from 15.9% (178/1123) before the action phase of the audit cycle; to 11.1% (107/966) during the action phase of the audit cycle with the doctors; to 2.4% (28/1182) with the registered midwife; to 0.9% (9/999) from three to nine months after the departure of the registered midwife, (p < 0.001, linear trend). Significant improvements in safe practice were observed at all three SMRU birth facilities. Knowledge of fetal nuchal cord amongst SBAs was sub-optimal and associated with fear and worry despite improved practice. The support of a registered midwife increased confidence of SBAs., Conclusion: The audit cycle and registered midwife interprofessional learning for SBAs led to a significant improvement in safe practice for the fetus with nuchal cord. The authors would encourage this type of learning in organizations with birth facilities on the Thai-Burmese border and in other similar resource limited settings with SBAs.

Background: Antenatal ultrasound suits developing countries by virtue of its versatility, relatively low cost and safety, but little is known about women's or local provider's perspectives of this upcoming technology in such settings. This study was undertaken to better understand how routine obstetric ultrasound is experienced in a displaced Burmese population and identify barriers to its acceptance by local patients and providers., Methodology/principal Findings: Qualitative (30 observations, 19 interviews, seven focus group discussions) and quantitative methods (questionnaire survey with 644 pregnant women) were used to provide a comprehensive understanding along four major themes: safety, emotions, information and communication, and unintended consequences of antenatal ultrasound in refugee and migrant clinics on the Thai Burmese border. One of the main concerns expressed by women was the danger of childbirth which they mainly attributed to fetal malposition. Both providers and patients recognized ultrasound as a technology improving the safety of pregnancy and delivery. A minority of patients experienced transitory shyness or anxiety before the ultrasound, but reported that these feelings could be ameliorated with improved patient information and staff communication. Unintended consequences of overuse and gender selective abortions in this population were not common., Conclusions/significance: The results of this study are being used to improve local practice and allow development of explanatory materials for this population with low literacy. We strongly encourage facilities introducing new technology in resource poor settings to assess acceptability through similar inquiry.