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Introduction: Severe neonatal hyperbilirubinaemia can place a neonate at risk for acute bilirubin encephalopathy and kernicterus spectrum disorder. Early diagnosis is essential to prevent these deleterious sequelae. Currently, screening by visual inspection followed by laboratory-based bilirubin (LBB) quantification is used to identify hyperbilirubinaemia in neonates cared for at home in the Netherlands. However, the reliability of visual inspection is limited. We aim to evaluate the effectiveness of universal transcutaneous bilirubin (TcB) screening as compared with visual inspection to: (1) increase the detection of hyperbilirubinaemia necessitating treatment, and (2) reduce the need for heel pricks to quantify bilirubin levels. In parallel, we will evaluate a smartphone app (Picterus), and a point-of-care device for quantifying total bilirubin (Bilistick) as compared with LBB., Methods and Analysis: We will undertake a multicentre prospective cohort study in nine midwifery practices across the Netherlands. Neonates born at a gestational age of 35 weeks or more are eligible if they: (1) are at home at any time between days 2 and 8 of life; (2) have their first midwife visit prior to postnatal day 6 and (3) did not previously receive phototherapy. TcB and the Picterus app will be used after visual inspection. When LBB is deemed necessary based on visual inspection and/or TcB reading, Bilistick will be used in parallel. The coprimary endpoints of the study are: (1) hyperbilirubinaemia necessitating treatment; (2) the number of heel pricks performed to quantify LBB. We aim to include 2310 neonates in a 2-year period. Using a decision tree model, a cost-effectiveness analysis will be performed., Ethics and Dissemination: This study has been approved by the Medical Research Ethical Committee of the Erasmus MC Rotterdam, Netherlands (MEC-2020-0618). Parents will provide written informed consent. The results of this study will be published in peer-reviewed journals., Trial Registration Number: Dutch Trial Register (NL9545)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe characteristics of neonates with severe neonatal hyperbilirubinaemia (SNH) and to gain more insight in improvable factors that may have contributed to the development of SNH., Design and Setting: Descriptive study, based on national Dutch perinatal audit data on SNH from 2017 to 2019., Patients: Neonates, born ≥35 weeks of gestation and without antenatally known severe blood group incompatibility, who developed hyperbilirubinaemia above the exchange transfusion threshold., Main Outcome Measures: Characteristics of neonates having SNH and corresponding improvable factors., Results: During the 3-year period, 109 neonates met the eligibility criteria. ABO antagonism was the most frequent cause (43%). All neonates received intensive phototherapy and 30 neonates (28%) received an exchange transfusion. Improvable factors were mainly related to lack of knowledge, poor adherence to the national hyperbilirubinaemia guideline, and to incomplete documentation and insufficient communication of the a priori hyperbilirubinaemia risk assessment among healthcare providers. A priori risk assessment, a key recommendation in the national hyperbilirubinaemia guideline, was documented in only six neonates (6%)., Conclusions: SNH remains a serious threat to neonatal health in the Netherlands. ABO antagonism frequently underlies SNH. Lack of compliance to the national guideline including insufficient a priori hyperbilirubinaemia risk assessment, and communication among healthcare providers are important improvable factors. Implementation of universal bilirubin screening and better documentation of the risk of hyperbilirubinaemia may enhance early recognition of potentially dangerous neonatal jaundice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Jaundice caused by hyperbilirubinaemia is a common phenomenon during the neonatal period. Population-based studies evaluating assessment, management, and incidence of jaundice and need for phototherapy among otherwise healthy neonates are scarce. We prospectively explored these aspects in a primary care setting via assessing care as usual during the control phase of a stepped wedge cluster randomised controlled trial.We conducted a prospective cohort study embedded in the Screening and TreAtment to Reduce Severe Hyperbilirubinaemia in Infants in Primary care (STARSHIP) Trial. Healthy neonates were included in seven primary care birth centres (PCBCs) in the Netherlands between July 2018 and March 2020. Neonates were eligible for inclusion if their gestational age was ≥ 35 weeks, they were admitted in a PCBC for at least  2 days during the first week of life, and if they did not previously receive phototherapy. Outcomes were the findings of visual assessment to detect jaundice, jaundice incidence and management, and the need for phototherapy treatment in the primary care setting.860 neonates were included of whom 608 (71.9%) were visibly jaundiced at some point during admission in the PCBC, with 20 being 'very yellow'. Of the latter, four (20%) did not receive total serum bilirubin (TSB) quantification. TSB levels were not associated with the degree of visible jaundice (p = 0.416). Thirty-one neonates (3.6%) received phototherapy and none received an exchange transfusion. Five neonates did not receive phototherapy despite having a TSB level above phototherapy threshold.Jaundice is common in otherwise healthy neonates cared for in primary care. TSB quantification was not always performed in very jaundiced neonates, and not all neonates received phototherapy when indicated. Quality improvement initiatives are required, including alternative approaches to identifying potentially severe hyperbilirubinaemia.Trial registration: NL6997 (Dutch Trial Register; Old NTR ID 7187), registered 3 May 2018., (© 2022. The Author(s).)

Background: Neonatal hyperbilirubinaemia is a physiologic phenomenon, but, when severe, may cause lifelong disability. Maternity care assistants (MCAs) play an important role in timely recognition of severe neonatal jaundice. We assessed knowledge and skills of MCAs regarding neonatal hyperbilirubinaemia., Methods: All Dutch MCAs (n = 9065) were invited to fill out a questionnaire assessing knowledge, expertise, and handling of neonatal jaundice. Additionally, we developed an e-learning and provided training sessions to a subgroup of MCAs (n = 99), and assessed their knowledge on neonatal hyperbilirubinaemia before and after the training., Results: One thousand four hundred sixty-five unique online questionnaires were completed (response 16.2%). The median number of correctly answered knowledge questions was 5 (out of six; IQR 1). Knowledge was significantly better when respondents had had in-service training on neonatal hyperbilirubinaemia in the previous year (p = 0.024). Although 82% of respondents felt highly skilled or skilled to assess jaundice, accuracy of estimation of total serum bilirubin levels by assessing skin colour was generally poor and prone to underestimation. Among participants attending a training session, those who completed the e-learning beforehand had higher pre-training scores (5 (IQR 1) vs. 4 (IQR 2); p < 0.001). The median post-training score was higher than pre-training (6 (IQR 1) vs. 5 (IQR 2); p < 0.001)., Conclusions: Background knowledge of MCAs regarding neonatal hyperbilirubinaemia was adequate, but can be improved by further training. Estimation of total serum bilirubin levels based on skin colour was often inadequate. Approaches to improve timely recognition of jaundiced neonates are needed.

Introduction: Jaundice caused by hyperbilirubinaemia is a physiological phenomenon in the neonatal period. However, severe hyperbilirubinaemia, when left untreated, may cause kernicterus, a severe condition resulting in lifelong neurological disabilities. Although commonly applied, visual inspection is ineffective in identifying severe hyperbilirubinaemia. We aim to investigate whether among babies cared for in primary care: (1) transcutaneous bilirubin (TcB) screening can help reduce severe hyperbilirubinaemia and (2) primary care-based (versus hospital-based) phototherapy can help reduce hospital admissions., Methods and Analysis: A factorial stepped-wedge cluster randomised controlled trial will be conducted in seven Dutch primary care birth centres (PCBC). Neonates born after 35 weeks of gestation and cared for at a participating PCBC for at least 2 days within the first week of life are eligible, provided they have not received phototherapy before. According to the stepped-wedge design, following a phase of 'usual care' (visual assessment and selective total serum bilirubin (TSB) quantification), either daily TcB measurement or, if indicated, phototherapy in the PCBC will be implemented (phase II). In phase III, both interventions will be evaluated in each PCBC. We aim to include 5500 neonates over 3 years.Primary outcomes are assessed at 14 days of life: (1) the proportion of neonates having experienced severe hyperbilirubinaemia (for the TcB screening intervention), defined as a TSB above the mean of the phototherapy and the exchange transfusion threshold and (2) the proportion of neonates having required hospital admission for hyperbilirubinaemia treatment (for the phototherapy intervention in primary care)., Ethics and Dissemination: This study has been approved by the Medical Research Ethics Committee of the Erasmus MC Rotterdam, the Netherlands (MEC-2017-473). Written parental informed consent will be obtained. Results from this study will be published in peer-reviewed journals and presented at (inter)national meetings., Trial Registration Number: NTR7187., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93-80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage.