SARS-CoV-2 Infection in Children Less Than Forty Days Hospitalized in Belgium Between 2020 and 2022.

Our study aimed to assess the severity of severe acute respiratory syndrome coronavirus 2 infection in hospitalized infants under 40 days old, across 21 Belgian hospitals between 2020 and 2022. Of the 365 infants studied, 14.2% needed respiratory support. The median hospital stay was 3 days (interquartile range, 2-4), and there were no deaths. Infection severity was similar during the Omicron and Alpha/Delta periods.

Contribution of genetic factors to high rates of neonatal hyperbilirubinaemia on the Thailand-Myanmar border.

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.

High levels of pathological jaundice in the first 24 hours and neonatal hyperbilirubinaemia in an epidemiological cohort study on the Thailand-Myanmar border.

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.

Extreme neonatal hyperbilirubinaemia in refugee and migrant populations: retrospective cohort.

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.

Maternal Hepatitis B Infection Burden, Comorbidity and Pregnancy Outcome in a Low-Income Population on the Myanmar-Thailand Border: A Retrospective Cohort Study.

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.

Laboratory validation and field usability assessment of a point-of-care test for serum bilirubin levels in neonates in a tropical setting.

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.

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

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

Neonatal Hyperbilirubinemia in a Marginalized Population on the Thai-Myanmar Border: a study protocol.

BACKGROUND: This study aims to identify risk factors and the neurodevelopmental impact of neonatal hyperbilirubinemia in a limited-resource setting among a refugee and migrant population residing along the Thai-Myanmar border, an area with a high prevalence of glucose-6-phosphate dehydrogenase-deficiency. METHODS: This is an analytic, observational, prospective birth cohort study including all infants of estimated gestational age equal to or greater than 28 weeks from mothers who followed antenatal care in the Shoklo Malaria Research Unit clinics. At birth, a series of clinical exams and laboratory investigations on cord blood will be carried out. Serum bilirubin will be measured in all infants during their first week of life. All the infants of the cohort will be clinically followed until the age of one year, including monitoring of their neurodevelopment. DISCUSSION: The strength of this study is the prospective cohort design. It will allow us to collect information about the pregnancy and detect all infants with neonatal hyperbilirubinemia, to observe their clinical response under treatment and to compare their neurodevelopment with infants who did not develop neonatal hyperbilirubinemia. Our study design has some limitations in particular the generalizability of our findings will be limited to infants born after the gestational age of 28 weeks onwards and neurodevelopment to the end of the first year of life. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02361788 , registration date September 1st, 2014.