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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.)

Aim: The study assessed mothers, children and adolescents' health (MCAH) outcomes in the context of a Primary Health Care (PHC) project and associated costs in two protracted long-term refugee camps, along the Thai-Myanmar border., Background: Myanmar refugees settled in Thailand nearly 40 years ago, in a string of camps along the border, where they fully depend on external support for health and social services. Between 2000 and 2018, a single international NGO has been implementing an integrated PHC project., Methods: This retrospective study looked at the trends of MCAH indicators of mortality and morbidity and compared them to the sustainable development goals (SDGs) indicators. A review of programme documents explored and triangulated the evolution and changing context of the PHC services, and associated project costs were analysed. To verify changes over time, interviews with 12 key informants were conducted., Findings: While maternal mortality (SDG3.1) remained high at 126.5/100,000 live births, child mortality (SDG 3.2) and infectious diseases in children under 5 (SDG 3.3) fell by 69% and by up to 92%, respectively. Maternal anaemia decreased by 30%; and more than 90% of pregnant women attended four or more antenatal care visits, whereas 80% delivered by a skilled birth attendant; caesarean section rates rose but remained low at an average of 3.7%; the adolescent (15-19 years) birth rate peaked at 188 per 1000 in 2015 but declined to 89/1000 in 2018 (SDG 3.7)., Conclusion: Comprehensive PHC delivery, with improved health provider competence in MCAH care, together with secured funding is an appropriate strategy to bring MCAH indicators to acceptable levels. However, inequities due to confinement in camps, fragmentation of specific health services, prevent fulfilment of the 2030 SDG Agenda to 'Leave no one behind'. Costs per birth was 115 EURO in 2018; however, MCAH expenditure requires further exploration over a longer period.

Background: The COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines., Methods: Ministries of Health or accessed National Infectious Disease websites and other relevant bodies and experts were contacted to obtain national guidelines (NGs) for COVID-19 treatment. NGs were included only if they delineated specific pharmacological treatments for COVID-19, which were stratified by disease severity. We conducted a retrospective review using the adapted Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG) survey checklist and a derived comparative metric based on the WHO guidelines was performed., Results: COVID-19 therapeutics NGs could be obtained from 109 of the 194 WHO member states. There was considerable variation in guidelines and in disease severity stratifications. Therapeutic recommendations in many NGs differed substantially from the WHO guidelines. Overall in late 2022, 93% of NGs were recommending at least one treatment which had proved to be ineffective in large randomised trials, and was not recommended by WHO. Corticosteroids were not recommended in severe disease in nearly 10% of NGs despite overwhelming evidence of their benefit. NGs from countries with low-resource settings showed the greatest divergence when stratified by gross domestic product per year, Human Development Index and the Global Health Security Index., Discussion: Our study is limited to NGs that were readily accessible, and it does not reflect the availability of recommended medicines in the field. Three years after the start of the SARS-CoV-2 pandemic, available COVID-19 NGs vary substantially in their therapeutic recommendations, often differ from the WHO guidelines, and commonly recommend ineffective, unaffordable or unavailable medicines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Selection of resistant malaria strains occurs when parasites are exposed to inadequate antimalarial drug concentrations. The proportion of uncomplicated falciparum malaria patients at risk of being sub-optimally dosed with the current World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs) is unknown. This study aims to estimate this proportion and the excess number of treatment failures (recrudescences) associated with sub-optimal dosing in Sub-Saharan Africa. Sub-populations at risk of sub-optimal dosing include wasted children <5 years of age, patients with hyperparasitaemia, pregnant women, people living with HIV, and overweight adults. Country-level data on population structure were extracted from openly accessible data sources. Pooled adjusted Hazard Ratios for PCR-confirmed recrudescence were estimated for each risk group from published meta-analyses using fixed-effect meta-analysis. In 2020, of the estimated 153.1 million uncomplicated P. falciparum malaria patients in Africa, the largest risk groups were the hyperparasitaemic patients (13.2 million, 8.6% of uncomplicated malaria cases) and overweight adults (10.3 million, 6.7% of uncomplicated cases). The estimated excess total number of treatment failures ranged from 0.338 million for a 98% baseline ACT efficacy to 1.352 million for a 92% baseline ACT efficacy. Our study shows that an estimated nearly 1 in 4 people with uncomplicated confirmed P. falciparum malaria in Africa are at risk of receiving a sub-optimal antimalarial drug dosing. This increases the risk of antimalarial drug resistance and poses a serious threat to malaria control and elimination efforts. Changes in antimalarial dosing or treatment duration of current antimalarials may be needed and new antimalarials development should ensure sufficient drug concentration levels in these sub-populations that carry a high malaria burden., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Takyi 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: Preterm birth is a major public health concern with the largest burden of morbidity and mortality falling within low- and middle-income countries (LMIC)., Materials and Methods: This sequential explanatory mixed methods study was conducted in special care baby units (SCBUs) serving migrants and refugees along the Myanmar-Thailand border. It included a retrospective medical records review, qualitative interviews with mothers receiving care within SCBUs, and focus group discussions with health workers. Changes in neonatal mortality and four clinical outcomes were described. A mix of ethnographic phenomenology and implementation frameworks focused on cultural aspects, the lived experience of participants, and implementation outcomes related to SCBU care., Results: From 2008-2017, mortality was reduced by 68% and 53% in very (EGA 28-32 weeks) and moderate (EGA 33-36 weeks) preterm neonates, respectively. Median SCBU stay was longer in very compared to moderate preterm neonates: 35 (IQR 22, 48 days) vs. 10 days (IQR 5, 16). Duration of treatments was also longer in very preterm neonates: nasogastric feeding lasted 82% (IQR 74, 89) vs. 61% (IQR 40, 76) of the stay, and oxygen therapy was used a median of 14 (IQR 7, 27) vs. 2 (IQR 1, 6) days respectively. Nine interviews were conducted with mothers currently receiving care in the SCBU and four focus group discussions with a total of 27 local SCBU staff. Analysis corroborated quantitative analysis of newborn care services in this setting and incorporated pertinent implementation constructs including coverage, acceptability, appropriateness, feasibility, and fidelity. Coverage, acceptability, and appropriateness were often overlapping outcomes of interest highlighting financial issues prior to or while admitted to the SCBU and social issues and support systems adversely impacting SCBU stays. Interview and FGD findings highlight the barriers in this resource-limited setting as they impact the feasibility and fidelity of providing evidence-based SCBU care that often required adaptation to fit the financial and environmental constraints imposed by this setting., Discussion: This study provides an in-depth look at the nature of providing preterm neonatal interventions in a SCBU for a vulnerable population in a resource-limited setting. These findings support implementation of basic evidence-based interventions for preterm and newborn care globally, particularly in LMICs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hashmi, Darakamon, Aung, Mu, Misa, Jittamala, Chu, Phyo, Turner, Nosten, McGready and Carrara.)

Very high unconjugated bilirubin plasma concentrations in neonates (neonatal hyperbilirubinaemia; NH) may cause neurologic damage (kernicterus). Both increased red blood cell turn-over and immaturity of hepatic glucuronidation contribute to neonatal hyperbilirubinaemia. The incidence of NH requiring phototherapy during the first week of life on the Thailand-Myanmar border is high (approximately 25%). On the Thailand-Myanmar border we investigated the contribution of genetic risk factors to high bilirubin levels in the first month of life in 1596 neonates enrolled in a prospective observational birth cohort study. Lower gestational age (<38 weeks), mutations in the genes encoding glucose-6-phosphate dehydrogenase (G6PD) and uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A1 were identified as the main independent risk factors for NH in the first week, and for prolonged jaundice in the first month of life. Population attributable risks (PAR%) were 61.7% for lower gestational age, 22.9% for hemi or homozygous and 9.9% for heterozygous G6PD deficiency respectively, and 6.3% for UGT1A1*6 homozygosity. In neonates with an estimated gestational age ≥ 38 weeks, G6PD mutations contributed PARs of 38.1% and 23.6% for "early" (≤ 48 hours) and "late" (49-168 hours) NH respectively. For late NH, the PAR for UGT1A1*6 homozygosity was 7.7%. Maternal excess weight was also a significant risk factor for "early" NH while maternal mutations on the beta-globin gene, prolonged rupture of membranes, large haematomas and neonatal sepsis were risk factors for "late" NH. For prolonged jaundice during the first month of life, G6PD mutations and UGT1A1*6 mutation, together with lower gestational age at birth and presence of haematoma were significant risk factors. In this population, genetic factors contribute considerably to the high risk of NH. Diagnostic tools to identify G6PD deficiency at birth would facilitate early recognition of high risk cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Bancone 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.)

Population risks for neonatal hyperbilirubinaemia (NH) vary. Knowledge of local risks permits interventions that may reduce the proportion becoming severe. Between January 2015 and May 2016, in a resource-limited setting on the Thailand-Myanmar border, neonates from 28 weeks' gestation were enrolled into a prospective birth cohort. Each neonate had total serum bilirubin measurements: scheduled (24, 48, 72 and 144 hours of life) and clinically indicated; and weekly follow up until 1 month of age. Risk factors for developing NH were evaluated using Cox proportional hazard mixed model. Of 1710 neonates, 22% (376) developed NH (83% preterm, 19% term). All neonates born <35 weeks, four in five born 35-37 weeks, and three in twenty born ≥38 weeks had NH, giving an overall incidence of 249 per 1000 livebirths [95%CI 225, 403]. Mortality from acute bilirubin encephalopathy was 10% (2/20) amongst the 5.3% (20/376) who reached the severe NH threshold. One-quarter (26.3%) of NH occurred within 24 hours. NH onset varied with gestational age: at a median [IQR] 24 hours [24, 30] for neonates born 37 weeks or prematurely vs 59 hours [48, 84] for neonates born ≥38 weeks. Risk factors for NH in the first week of life independent of gestational age were: neonatal G6PD deficiency, birth bruising, Sgaw Karen ethnicity, primigravidae, pre-eclampsia, and prolonged rupture of membranes. The genetic impact of G6PD deficiency on NH was partially interpreted by using the florescent spot test and further genotyping work is in progress. The risk of NH in Sgaw Karen refugees may be overlooked internationally as they are most likely regarded as Burmese in countries of resettlement. Given high levels of pathological jaundice in the first 24 hours and overall high NH burden, guidelines changes were implemented including preventive PT for all neonates <35 weeks and for those 35-37 weeks with risk factors., Competing Interests: The authors have declared that no competing interests exist.

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.

Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections) 1 and preventive interventions (for example, multiple-micronutrient supplementation) 2 that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood 3 . In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites worldwide 4 , we studied the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks' gestation, against international standards 5,6 , and growth and neurodevelopment up to 2 years of age 7,8 . We identified five trajectories associated with specific neurodevelopmental, behavioral, visual and growth outcomes, independent of fetal abdominal growth, postnatal morbidity and anthropometric measures at birth and age 2. The trajectories, which changed within a 20-25-week gestational age window, were associated with brain development at 2 years of age according to a mirror (positive/negative) pattern, mostly focused on maturation of cognitive, language and visual skills. Further research should explore the potential for preventive interventions in pregnancy to improve infant neurodevelopmental outcomes before the critical window of opportunity that precedes the divergence of growth at 20-25 weeks' gestation.

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: There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial., Methods and Findings: A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0-29.0 years; range = 0-80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9-33.4) after AL, 14.1% (95% CI 10.8-18.3) after AA, 7.4% (95% CI 6.7-8.1) after AM, and 4.5% (95% CI 3.9-5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6-43.3), 42.4% (95% CI 34.7-51.2), 22.8% (95% CI 21.2-24.4), and 12.8% (95% CI 11.4-14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0-19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6-8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4-3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0-1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4-2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high., Conclusions: In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RMF is employed currently by AstraZeneca but has no financial stake in the results of the current study. EAA and NJW are Academic Editors on PLOS Medicine's editorial board, and IM was previously an Academic Editor.

Purpose: A successful pregnancy relies on the interplay of various biological systems. Deviations from the norm within a system or intersystemic interactions may result in pregnancy-associated complications and adverse pregnancy outcomes. Systems biology approaches provide an avenue of unbiased, in-depth phenotyping in health and disease. The molecular signature in pregnancy (MSP) cohort was established to characterise longitudinal, cross-omic trajectories in pregnant women from a resource constrained setting. Downstream analysis will focus on characterising physiological perturbations in uneventful pregnancies, pregnancy-associated complications and adverse outcomes., Participants: First trimester pregnant women of Karen or Burman ethnicity were followed prospectively throughout pregnancy, at delivery and until 3 months post partum. Serial high-frequency sampling to assess whole blood transcriptomics and microbiome composition of the gut, vagina and oral cavity, in conjunction with assessment of gene expression and microbial colonisation of gestational tissue, was done for all cohort participants., Findings to Date: 381 women with live born singletons averaged 16 (IQR 15-18) antenatal visits (13 094 biological samples were collected). At 5% (19/381) the preterm birth rate was low. Other adverse events such as maternal febrile illness 7.1% (27/381), gestational diabetes 13.1% (50/381), maternal anaemia 16.3% (62/381), maternal underweight 19.2% (73/381) and a neonate born small for gestational age 20.2% (77/381) were more often observed than preterm birth., Future Plans: Results from the MSP cohort will enable in-depth characterisation of cross-omic molecular trajectories in pregnancies from a population in a resource-constrained setting. Moreover, pregnancy-associated complications and unfavourable pregnancy outcomes will be investigated at the same granular level, with a particular focus on population relevant needs such as effect of tropical infections on pregnancy. More detailed knowledge on multiomic perturbations will ideally result in the development of diagnostic tools and ultimately lead to targeted interventions that may disproportionally benefit pregnant women from this resource-limited population., Trial Registration Number: NCT02797327., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe neonatal survival and long-term neurological outcome in neonatal hyperbilirubinaemia (NH) with extreme serum bilirubin (SBR) values., Design: Retrospective chart review, a one-off neurodevelopmental evaluation., Setting: Special care baby unit in a refugee camp and clinics for migrant populations at the Thailand-Myanmar border with phototherapy facilities but limited access to exchange transfusion (ET)., Patients: Neonates ≥28 weeks of gestational age with extreme SBR values and/or acute neurological symptoms, neurodevelopment evaluation conducted at 23-97 months of age., Main Outcome Measures: Neonatal mortality rate, prevalence of acute bilirubin encephalopathy (ABE) signs, prevalence of delayed development scores based on the Griffiths Mental Development Scale (GMDS)., Results: From 2009 to 2014, 1946 neonates were diagnosed with jaundice; 129 (6.6%) had extreme SBR values during NH (extreme NH). In this group, the median peak SBR was 430 (IQR 371-487) µmol/L and the prevalence of ABE was 28.2%. Extreme NH-related mortality was 10.9% (14/129). Median percentile GMDS general score of 37 survivors of extreme NH was poor: 11 (2-42). 'Performance', 'practical reasoning' and 'hearing and language' domains were most affected. Four (10.8%) extreme NH survivors had normal development scores (≥50th centile). Two (5.4%) developed the most severe form of kernicterus spectrum disorders., Conclusion: In this limited-resource setting, poor neonatal survival and neurodevelopmental outcomes, after extreme NH, were high. Early identification and adequate treatment of NH where ET is not readily available are key to minimising the risk of extreme SBR values or neurological symptoms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

All Plasmodium cases have declined over the last decade in northwestern Thailand along the Myanmar border. During this time, Plasmodium vivax has replaced Plasmodium falciparum as the dominant species. The decline in P. falciparum has been shadowed by a coincidental but delayed decline in P. vivax cases. This may be due to early detection and artemisinin-based therapy, species-specific diagnostics, and bed net usage all of which reduce malaria transmission but not P. vivax relapse. In the absence of widespread primaquine use for radical cure against P. vivax hypnozoites, the decline in P. vivax may be explained by decreased hypnozoite activation of P. vivax relapses triggered by P. falciparum . The observed trends in this region suggest a beneficial effect of decreased P. falciparum transmission on P. vivax incidence, but elimination of P. vivax in a timely manner likely requires radical cure.

Background: This study aims to provide a comprehensive understanding of maternal risk factors, infant risk factors and maternal infant feeding practices among refugees and migrants along the Thailand-Myanmar border., Methods: This study employed a mixed-methods approach with two components: (1) cross-sectional survey (n = 390) and (2) focus group discussions (n = 63). Participants were chosen from one of three clinics providing antenatal and delivery services for Karen and Burman refugees and migrants along the border. Participants were pregnant women and mother-infant dyads., Results: Refugee and migrant mothers demonstrated high rates of suboptimal breastfeeding and low rates of minimum dietary diversity and acceptable diet. Multivariable regression models showed infant stunting (AOR: 2.08, 95% CI: 1.12, 3.84, p = 0.020) and underweight (AOR: 2.26, 95% CI: 1.17, 4.36, p = 0.015) to have increased odds among migrants, while each 5 cm increase in maternal height had decreased odds of stunting (AOR: 0.50, 95% CI: 0.38, 0.66, p < 0.001) and underweight (AOR: 0.64, 95% CI: 0.48, 0.85, p = 0.002). In addition, small-for-gestational-age adjusted for length of gestation, infant age and gender increased odds of infant's stunting (AOR: 3.42, 95% CI: 1.88, 6.22, p < 0.001) and underweight (AOR: 4.44, 95% CI: 2.36, 8.34, p < 0.001). Using the Integrated Behavioural Model, focus group discussions explained the cross-sectional findings in characterising attitudes, perceived norms, and personal agency as they relate to maternal nutrition, infant malnutrition, and infant feeding practices., Conclusions: Inadequate infant feeding practices are widespread in refugee and migrant communities along the Thailand-Myanmar border. Risk factors particular to maternal nutrition and infant birth should be considered for future programming to reduce the burden of chronic malnutrition in infants.

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.

From 2003 through 2009, 687 of 2885 patients (23.8%) treated for Plasmodium falciparum malaria in clinical studies in Myanmar or on the Thailand-Myanmar border had recurrent Plasmodium vivax malaria within 63 days, compared with 18 of 429 patients (4.2%) from 2010 onward (risk ratio [RR], 0.176; 95% confidence interval, .112-.278; P < .0001). Corresponding data from 42 days of follow-up revealed that 820 of 3883 patients (21.1%) had recurrent P. vivax malaria before 2010, compared with 22 of 886 (2.5%) from 2010 onward (RR, 0.117; 95% CI, .077-.177; P < .0001). This 6-fold reduction suggests a recent decline in P. vivax transmission intensity and, thus, a substantial reduction in the proportion of individuals harboring hypnozoites., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

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.

Background: Primaquine is necessary for the radical cure of Plasmodium vivax malaria, but the optimum duration of treatment and best partner drug are uncertain. A randomized controlled trial was performed to compare the tolerability and radical curative efficacy of 7-day versus 14-day high-dose primaquine regimens (total dose 7mg/kg) with either chloroquine or dihydroartemisinin-piperaquine., Methods: Patients with uncomplicated P. vivax malaria on the Thailand-Myanmar border were randomized to either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine, either 0.5 mg/kg/day for 14 days or 1 mg/kg/day for 7 days. Adverse events within 42 days and 1-year recurrence rates were compared and their relationship with day 6 drug concentrations assessed., Results: Between February 2012 and July 2014, 680 patients were enrolled. P. vivax recurrences (all after day 35) occurred in 80/654 (12%) patients; there was no difference between treatments. Compared to the 7-day primaquine groups the pooled relative risk of recurrence in the 14-day groups was 1.15 (95% confidence interval 0.7 to 1.8). Hematocrit reductions were clinically insignificant except in G6PD female heterozygotes, 2 of whom had hematocrit reductions to <23% requiring blood transfusion., Conclusion: Radical cure should be deployed more widely. The radical curative efficacy in vivax malaria of 7-day high-dose primaquine is similar to the standard 14-day high-dose regimen. Chloroquine and dihydroartemisinin-piperaquine are both highly effective treatments of the blood stage infection. Quantitative point of care G6PD testing would ensure safe use of the 7-day high-dose primaquine regimen in G6PD heterozygous females., Clinical Trials Registration: NCT01640574., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

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.

Problems in growth and undernutrition manifest in early infancy, with suboptimal breastfeeding and inadequate complementary feeding remaining strong risk factors for chronic undernutrition in infants. No published studies exist on educational interventions to improve infant feeding practices among refugees or displaced persons in low and middle-income (LMIC) settings. The objective of this study was to create and pilot educational materials for home-based counseling of refugee mothers along the Thailand-Myanmar border to improve appropriate infant feeding and water, sanitation, and hygiene (WASH) behaviors. Mothers of infants received counseling on appropriate infant feeding and WASH practices on a monthly basis for a total of six months from infant age three months until nine months. Educational materials were designed to feature a basic script for health workers and photos of locally available, appropriate foods. Of the 20 mothers participating in this pilot, infant feeding and WASH behaviors improved within 1 to 2 months of the first visit, including exclusive breastfeeding, minimum acceptable diet, and safe disposal of infant stool. This pilot demonstrates improvement in maternal infant feeding and WASH practices in a small set of refugee mothers, providing evidence for counseling measures to improve infant health in vulnerable populations.

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.

Background :  No universal  demarcation of gestational age  distinguishes miscarriage and stillbirth or extreme preterm birth (exPTB). This study provides a synopsis of outcome between 22 to <28 weeks gestation from a low resource setting. Methods :  A retrospective record review of a population on the Thailand-Myanmar border was conducted. Outcomes were classified as miscarriage, late expulsion of products between 22 to < 28 weeks gestation with evidence of non-viability (mostly ultrasound absent fetal heart beat) prior to 22 weeks; or  exPTB (stillbirth/live born) between 22 to < 28 weeks gestation when the fetus was viable at ≥22 weeks. Termination of pregnancy and gestational trophoblastic disease were excluded. Results :  From 1995-2015, 80.9% (50,046/ 61,829) of registered women had a known pregnancy outcome, of whom 99.8% (49,931) had a known gestational age. Delivery  between 22 to <28 weeks gestation included 0.9% (472/49,931) of pregnancies after removing 18 cases (3.8%) who met an exclusion criteria. Most  pregnancies had an ultrasound: 72.5% (n=329/454);  43.6% (n=197) were classified as  miscarriage and 56.4% (n=257) exPTB.  Individual record review of miscarriages estimated that fetal death had occurred at a median of 16 weeks, despite late expulsion between 22 to <28 weeks. With available data (n=252, 5 missing) the proportion of stillbirth was 47.6% (n=120), congenital abnormality 10.5% (24/228, 29 missing) and neonatal death was 98.5% (128/131, 1 missing). Introduction of ultrasound was associated with a 2-times higher odds of classification of outcome as exPTB rather than miscarriage. Conclusion :  In this low resource setting few (<1%) pregnancy outcomes occurred in the 22 to <28 weeks gestational window; four in ten  were miscarriage (late expulsion) and neonatal mortality approached 100%.  In the scale-up to preventable newborns deaths (at least initially) greater benefits will be obtained by focusing on the viable newborns of ≥ 28 weeks gestation., Competing Interests: Competing interests: No competing interests were disclosed.

Background: Screening and monitoring serum bilirubin (SBR) in neonates is crucial to prevent neonatal hyperbilirubinemia (NH)-associated morbidity and mortality worldwide. A lack of resources is often a barrier for measuring SBR in developing countries. Reliable, cost-effective, easy to use point-of-care (POC) SBR tests are needed. This study aimed to evaluate the technical accuracy and usability of the Bilistick System (BS), a new bilirubin POC test, in a tropical setting. Methods: This was a mixed-methods study, including laboratory validation of the BS, direct observation of technical procedures as performed by the midwives and midwives' assessment of the device's easiness of use through focus group discussions (FGD) and a self-administered questionnaire. The study was conducted in a field clinic of the Shoklo Malaria Research Unit along the Thailand-Myanmar border between January and December 2017. Results: A total of 173 samples were tested at a median age of 4 days. BS generated an error message-providing no SBR readout-in 48.6% of the tests performed. For the tests that yielded a result, the correlation coefficient (95% CI) between BS and routine laboratory bilirubinometer SBR was 0.87 (0.77-0.93). The accuracy decreased with increasing haematocrit and at higher humidity (≥75%). Direct observation of the operators using the device and analysis of the focus group discussions and questionnaires indicated that the BS was considered easy to use and required limited training. Conclusions: This evaluation showed that the BS, in its current formulation, does not provide reliable results for measuring SBR in a tropical, low-resource setting  but has acceptable usability features., Competing Interests: No competing interests were disclosed.

Background: Chloroquine has been recommended for Plasmodium vivax infections for >60 years, but resistance is increasing. To guide future therapies, the cumulative benefits of using slowly eliminated (chloroquine) vs rapidly eliminated (artesunate) antimalarials, and the risks and benefits of adding radical cure (primaquine) were assessed in a 3-way randomized comparison conducted on the Thailand-Myanmar border., Methods: Patients with uncomplicated P. vivax malaria were given artesunate (2 mg/kg/day for 5 days), chloroquine (25 mg base/kg over 3 days), or chloroquine-primaquine (0.5 mg/kg/day for 14 days) and were followed for 1 year. Recurrence rates and their effects on anemia were compared., Results: Between May 2010 and October 2012, 644 patients were enrolled. Artesunate cleared parasitemia significantly faster than chloroquine. Day 28 recurrence rates were 50% with artesunate (112/224), 8% with chloroquine (18/222; P < .001), and 0.5% with chloroquine-primaquine (1/198; P < .001). Median times to first recurrence were 28 days (interquartile range [IQR], 21-42) with artesunate, 49 days (IQR, 35-74) with chloroquine, and 195 days (IQR, 82-281) with chloroquine-primaquine. Recurrence by day 28, was associated with a mean absolute reduction in hematocrit of 1% (95% confidence interval [CI], .3%-2.0%; P = .009). Primaquine radical cure reduced the total recurrences by 92.4%. One-year recurrence rates were 4.51 (95% CI, 4.19-4.85) per person-year with artesunate, 3.45 (95% CI, 3.18-3.75) with chloroquine (P = .002), and 0.26 (95% CI, .19-.36) with chloroquine-primaquine (P < .001)., Conclusions: Vivax malaria relapses are predominantly delayed by chloroquine but prevented by primaquine., Clinical Trials Registration: NCT01074905.

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.

Background: Indirect neonatal hyperbilirubinemia (INH) is a common neonatal disorder worldwide which can remain benign if prompt management is available. However there is a higher morbidity and mortality risk in settings with limited access to diagnosis and care. The manuscript describes the characteristics of neonates with INH, the burden of severe INH and identifies factors associated with severity in a resource-constrained setting., Methods: We conducted a retrospective evaluation of anonymized records of neonates hospitalized on the Thai-Myanmar border. INH was defined according to the National Institute for Health and Care Excellence guidelines as 'moderate' if at least one serum bilirubin (SBR) value exceeded the phototherapy threshold and as 'severe' if above the exchange transfusion threshold., Results: Out of 2980 records reviewed, 1580 (53%) had INH within the first 14 days of life. INH was moderate in 87% (1368/1580) and severe in 13% (212/1580). From 2009 to 2011, the proportion of severe INH decreased from 37 to 15% and the mortality dropped from 10% (8/82) to 2% (7/449) coinciding with the implementation of standardized guidelines and light-emitting diode (LED) phototherapy. Severe INH was associated with: prematurity (< 32 weeks, Adjusted Odds Ratio (AOR) 3.3; 95% CI 1.6-6.6 and 32 to 37 weeks, AOR 2.2; 95% CI 1.6-3.1), Glucose-6-phosphate dehydrogenase deficiency (G6PD) (AOR 2.3; 95% CI 1.6-3.3), potential ABO incompatibility (AOR 1.5; 95% CI 1.0-2.2) and late presentation (AOR 1.8; 95% CI 1.3-2.6). The risk of developing severe INH and INH-related mortality significantly increased with each additional risk factor., Conclusion: INH is an important cause of neonatal hospitalization on the Thai-Myanmar border. Risk factors for severity were similar to previous reports from Asia. Implementing standardized guidelines and appropriate treatment was successful in reducing mortality and severity. Accessing to basic neonatal care including SBR testing, LED phototherapy and G6PD screening can contribute to improve neonatal outcomes.

Background: Of the 4 million neonatal deaths worldwide yearly, 98% occur in low and middle-income countries. Effective resuscitation reduces mortality and morbidity but long-term outcomes in resource-limited settings are poorly described. This study reports on newborn neurological outcomes following resuscitation at birth in a resource-limited setting where intensive newborn care including intubation is unavailable., Methods: Retrospective analysis of births records from 2008 to 2015 at Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border., Findings: From 21,225 newbonrs delivered, 15,073 (71%) met the inclusion criteria (liveborn, singleton, ≥28 weeks' gestation, delivered in SMRU). Neonatal resuscitation was performed in 460 (3%; 422 basic, 38 advanced) cases. Overall early neonatal mortality was 6.6 deaths per 1000 live births (95% CI 5.40-8.06). Newborns receiving basic and advanced resuscitation presented an adjusted rate for death of 1.30 (95%CI 0.66-2.55; p = 0.442), and 6.32 (95%CI 3.01-13.26; p<0.001) respectively, compared to newborns given routine care. Main factors related to increased need for resuscitation were breech delivery, meconium, and fetal distress (p<0.001). Neurodevelopmental follow-up to one year was performed in 1,608 (10.5%) of the 15,073 newborns; median neurodevelopmental scores of non-resuscitated newborns and those receiving basic resuscitation were similar (64 (n = 1565) versus 63 (n = 41); p = 0.732), while advanced resuscitation scores were significantly lower (56 (n = 5); p = 0.017)., Interpretations: Newborns requiring basic resuscitation at birth have normal neuro-developmental outcomes at one year of age compared to low-risk newborns. Identification of risk factors (e.g., breech delivery) associated with increased need for neonatal resuscitation may facilitate allocation of staff to high-risk deliveries. This work endorses the use of basic resuscitation in low-resource settings, and supports on-going staff training to maintain bag-and-mask ventilation skills.