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Introduction Retinopathy of prematurity (ROP) is a serious eye disease in preterm infants. Generally, the progression of this disease can be detected by screening infants regularly. In case of progression, treatment can be instituted to stop the progression. In Indonesia, however, not all infants are screened because the number of pediatric ophthalmologists trained to screen for ROP and provide treatment is limited. Therefore, other methods are required to identify infants at risk of developing severe ROP. Objective To assess a scoring model’s internal and external validity to predict ROP progression in Indonesia. Method To develop a scoring model and determine its internal validity, we used data on 98 preterm infants with ROP who had undergone one or more serial eye examinations between 2009 and 2014. For external validation, we analyzed data on 62 infants diagnosed with ROP irrespective of the stage between 2017 and 2020. Patients stemmed from one neonatal unit and three eye clinics in Jakarta, Indonesia. Results We identified the duration of oxygen supplementation, gestational age, socio-economic status, place of birth, and oxygen saturation monitor setting as risk factors for developing ROP. We developed two models—one based on the duration of supplemental oxygen and one on the setting of the oxygen saturation monitor. The ROP risk and probabilistic models obtained the same sensitivity and specificity for progression to Type 1 ROP. The agreement, determined with the Kappa statistic, between the ROP risk model’s suitability and the probabilistic model was excellent. The external validity of the ROP risk model showed 100% sensitivity, 73% specificity, 76% positive predictive value, 100% negative predictive value, positive LR +3.7, negative LR 0, 47% pre-test probability, and 77% post-test probability. Conclusion The ROP risk scoring model can help to predict which infants with first-stage ROP might show progression to severe ROP and may identify infants who require referral to a pediatric ophthalmologist for treatment.

Background Severe hyperbilirubinemia is more frequent in low- and middle-income countries such as Indonesia than in high-income countries. One of the contributing factors might be the lack of adherence to existing guidelines on the diagnosis and treatment of hyperbilirubinemia. We developed a new national guideline for hyperbilirubinemia management in Indonesia. To help healthcare workers use this guideline, a web-based decision support tool application may improve both the adherence to the guideline and the care for infants with hyperbilirubinemia. Methods We developed a web-based application (BiliNorm) to be used on a smartphone that displays the bilirubin level of the patient on the nomogram and advises about the treatment that should be started. Healthcare workers of two teaching hospitals in East Java, Indonesia, were trained on the use of BiliNorm. At 6 months after the introduction, a questionnaire was sent to those who worked with the application enquiring about their experiences. An observational study was conducted in two time epochs. A chart review of infants with hyperbilirubinemia in the two hospitals was sent. The appropriateness of hyperbilirubinemia management during a 6-month period before BiliNorm introduction was compared to that during a 7-month period after its introduction. Results A total of 43 participants filled in the questionnaire, the majority (72%) of them indicated that BiliNorm was well received and easy to use. Moreover, 84% indicated that BiliNorm was helpful for the decision to start phototherapy. Chart review of 255 infants before BiliNorm introduction and that of 181 infants after its introduction indicated that significantly more infants had received treatment according to the guideline (38% vs 51%, p = 0.006). Few infants received phototherapy, but bilirubin level was not measured (14% vs 7%, p = 0.024). There was no difference in the proportion of infants who were over- and under-treated (34% vs 32% and 14% vs 10%, respectively). Conclusions The web-based decision tool BiliNorm appears to be a valuable application. It is easy to use for healthcare workers and helps them adhere to the guideline. It improves the care for infants with hyperbilirubinemia and may help reduce the incidence of severe hyperbilirubinemia in Indonesia.

ObjectiveMorphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.Study designTerm and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008-2010 (SHIVER) and 2010-2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.Results244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C- 8.41%/°C, pConclusionsClearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.Trial registrationwww.trialregister.nl NTR2529.

Severe hyperbilirubinemia, which may result in kernicterus, is seen more frequently in low and middle-income countries, such as Indonesia, than in high-income countries. In Indonesia midwives, general practitioners (GPs), and pediatricians are involved in the care of jaundiced newborn infants. It is unknown whether the high incidence of severe hyperbilirubinemia in this country is related to a lack of awareness of existing hyperbilirubinemia guidelines issued by, for example, the World Health Organization, the American Academy of Pediatrics, or the Indonesian Health Ministry, or to a lack of adherence to such guidelines. The aim of this questionnaire study was to assess health professionals' awareness of existing guidelines and their adherence to these guidelines in daily practice. We handed out a ten-question questionnaire to midwives, GPs, and pediatricians that included questions about the professionals themselves as well as clinical questions. The midwives completed 291 questionnaires, the GPs 206, and the pediatricians 154, all of which we used for our analysis. Almost 30% of the midwives and 23% of the GPs were either unaware of any existing guidelines or they did not adhere to them. Only 54% of the midwives recognized the warning signs of severe hyperbilirubinemia correctly, compared to 68% of the GPs and 89% of the pediatricians. Twenty-eight percent of the midwives and 31% of the GPs indicated that their first follow-up visit was after 72 hours, while 90% of them discharged infants after less than 48 hours after birth. The awareness of and adherence to guidelines for preventing and treating hyperbilirubinemia is low amongst the midwives and GPs in Indonesia. This may be an important contributing factor in the high incidence of severe hyperbilirubinemia in Indonesia.

To test the ability of the Ages and Stages Questionnaire, Third Edition (ASQ3) to help identify or exclude neurodevelopmental impairment (NDI) in very preterm-born children at the corrected age of two.We studied the test results of 224 children, born at

High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death.Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g.The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome.Controlled-Trials.com ISRCTN74465643.

BACKGROUND: Severe unconjugated hyperbilirubinemia may cause deafness. In the Netherlands, 25% lower total serum bilirubin (TSB) treatment thresholds were recently implemented for preterm infants. OBJECTIVE: To determine the rate of hearing loss in jaundiced preterms treated at high or at low TSB thresholds. DESIGN/METHODS: In this retrospective study conducted at two neonatal intensive care units in the Netherlands, we included preterms (gestational age 35 dB). RESULTS: There were 479 patients in the high and 144 in the low threshold group. Both groups had similar gestational ages (29.5 weeks) and birth weights (1300 g). Mean and mean peak TSB levels were significantly lower after the implementation of the novel thresholds: 152 ± 43 µmol/L and 212 ± 52 µmol/L versus 131 ± 37 µmol/L and 188 ± 46 µmol/L for the high versus low thresholds, respectively (P