Christian Victor Hulzebos

Background: Sufficient irradiance levels of phototherapy (PT) devices are essential for the efficacy of PT. Yet, irradiance levels are infrequently measured, are sometimes lower than recommended, and little is known about whether improvement over time occurs. Aim: To investigate the irradiance levels of PT devices in pediatric departments of all general hospitals in the Northern Netherlands in two different time epochs. Methods: Irradiance levels of all available PT devices were measured in eight pediatric departments in 2023, and median levels were compared with levels measured in 2017. The PT devices were positioned as they were routinely used. Two calibrated radiometers were used: the Dale 40 Phototherapy Radiometer (Fluke Biomedical, Everett, WA) and the Ohmeda Medical BiliBlanket Meter II (BBII, GE Healthcare, Chicago, IL). Results: Irradiance levels of overhead devices increased from 20 µW/cm²/nm in 2017 to 24 µW/cm²/nm in 2023 ( P = .021). The mean distance between the PT device and the silhouette decreased by 19 cm in 2023 ( P < .001). Irradiance of the devices underneath was similar in 2017 and 2023, that is, 25 (18-28) and 24 (11-34) µW/cm²/nm, respectively. There were no differences in median irradiance between hospitals. High-intensity irradiance levels >30 µW/cm²/nm were not possible for all devices, but more (66% in 2017; 97% in 2023) PT devices met the recommended minimum irradiance. Irradiance measurements of the BBII were significantly higher than those of the Dale 40 for underneath PT devices. Conclusions: Irradiance levels of PT devices in general hospitals increased over time, but high-intensity PT was not always possible. The observed improvement may be explained by the shorter distance between the PT device and the silhouette and the use of newer PT devices. Finally, the radiometer-specific irradiance measurements underline the importance of measuring irradiance with an appropriate radiometer.

Probiotics may reduce the risk of necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and mortality in preterm infants. However, their efficacy in extremely preterm infants (gestational age < 28 weeks) is still regularly questioned due to limited data and safety concerns. In Dutch Neonatal Intensive Care Units (NICUs), a three-strain probiotic product (ProPrems®; Bifidobacterium infantis Bb-02, Bifidobacterium lactis BB-12, and S treptococcus thermophilus TH-4) was implemented as standard of care from 2021 onwards. This study evaluates the clinical effects of these probiotics in extremely preterm infants. Pre- and postimplementation cohorts of extremely preterm infants from 6 Dutch NICUs (2018–2023) were compared. Clinical data from the first 29 days of life were collected. Incidence of NEC (modified Bell’s stage ≥ IIA), LOS, and mortality were compared with logistic regression; growth velocity with linear regression; and time to full enteral feeds (tFEF) with survival analyses. In total, 481 extremely preterm infants (212 pre-, 269 post-implementation) were included. After implementation, the adjusted odds ratio was 0.49 (0.25–0.99; p = 0.049) for NEC; 0.87 (0.59–1.28; p = 0.49) for LOS; and 0.67 (0.35–1.27; p = 0.22) for all-cause mortality. Furthermore, tFEF decreased by 2 days ( p < 0.001) and probiotic use was associated with an increase in growth velocity of 1.8 g/kg/day ( p < 0.001). One infant (0.4%) developed probiotic-associated sepsis. Conclusion : This multicenter pre-postimplementation study showed that multi-strain probiotic administration was associated with lower NEC incidence, shorter tFEF, and greater growth velocity in extremely preterm infants during the first four weeks of life. Probiotic-associated sepsis was rare. These results support continued use of probiotics in this vulnerable population. What is Known: • Certain probiotic strains effectively reduce incidence of necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety for extremely preterm infants (GA < 28 weeks) remain under debate. What is New: • This study shows that a multi-strain probiotic supplement was associated with lower NEC incidence, shorter time to full enteral feeds, and greater early postnatal growth in a Dutch multicenter cohort of extremely preterm infants. • The incidence of probiotic-associated sepsis in extremely preterm infants was very low in our cohort with just 1 case (0.4%), consistent with the rare occurrence reported previously.

Intestinal bacterial translocation to the bloodstream is a route of infection for late-onset sepsis (LOS) in preterm infants, highlighting the potential of fecal microbiota profiling for early risk stratification. We aimed to identify and validate LOS-specific gut microbiota signatures. Fifty-eight preterm infants (gestational age < 30 weeks) with blood culture-proven LOS (excluding coagulase-negative staphylococci) were matched to controls (1:1) across three cohorts (Discovery (DC) n = 18; Validation 1 and 2; VC1 n = 12, VC2 n = 28). Fecal samples collected up to 10 days before LOS onset underwent 16S rRNA gene sequencing. Microbial composition, diversity, and discriminatory taxa were compared across LOS subgroups. Random Forest (RF) models were trained in DC and validated in VC1/VC2. Microbiota variation was largely explained by LOS pathogen (R² = 17%, P < 0.001). Infants with non-staphylococcal and E. coli-LOS showed a temporal increase in relative abundance of Escherichia/Shigella. The RF model distinguishing E. coli-LOS from controls displayed the highest discriminatory performance (AUC = 0.99/0.78/0.61 for DC/VC1/VC2) compared to non-staphylococcal LOS (AUC = 0.96/0.46/0.41). Our findings demonstrate profound microbiota shifts preceding E. coli-LOS, with higher discriminatory ability compared to non-staphylococcal-LOS. While pathogen-specific microbiota-based risk stratification may offer added clinical value, reduced validation performance highlights the limited generalizability and underscores the need for future research before clinical translation.

Introduction: Sudden unexpected postnatal collapse (SUPC) is a rare and potentially life-threatening event with variable reported incidences, mostly derived from in-hospital data. This study investigated the incidence, aetiology, and circumstances of SUPC in the Netherlands and assessed differences between in-hospital and home settings. Methods: Data concerning SUPC cases were obtained through a web-based registry managed by the Dutch Paediatric Surveillance Unit from April 2019 to April 2022. SUPC was defined as a collapse within 24 h of birth requiring resuscitation with at least positive pressure ventilation in infants born at ≥35 weeks of gestation and with a 5-min Apgar score ≥8. Results: Of 94 registered SUPC cases, 60 met inclusion criteria: 52 cases occurred in hospital and 8 at home. The annual incidence ranged between 7 and 17 per 100,000 live births, with an average of 11 per 100,000. Median time to collapse was 64 min, with over two-thirds occurring within 2 h of birth. Collapses occurring at home occurred significantly later than those in hospital (165 min vs. 60 min; p < 0.05) and were associated with substantially higher mortality rates (37.5% vs. 6%; p < 0.05). Approximately half of all SUPC cases involved possible or definite airway obstruction, which – compared with other aetiologies – was more often related to preventable factors like reduced maternal vigilance and covering of the infant’s nose and mouth. Conclusions: SUPC occurs in hospitals and at home, with later onset and higher mortality outside the hospital. Greater awareness and prevention are needed in both settings.

Introduction: The Bilistick is a handheld point-of-care device for measuring total bilirubin levels in small blood volumes. We assessed its diagnostic accuracy and user convenience in near-term neonates cared for at home. Methods: A prospective cohort study was conducted in nine Dutch community midwifery practices. Neonates ≥35 weeks’ gestation were eligible if they were at home between postnatal days 2–8 and had not received phototherapy. A Bilistick version 2.0 was used in parallel to laboratory-based bilirubin (LBB) quantification when significant visible jaundice was observed or the transcutaneous bilirubin reading was elevated. Results: A total of 2,314 neonates were included in the study, with 423 blood samples analyzed across 13 laboratories. On 203 occasions, the Bilistick was not used. Among the remaining 220 Bilistick readings, 104 failed, and 2 lacked corresponding LBB results. A Bland-Altman plot of 114 paired measurements of Bilistick and LBB showed a mean difference of +9.7 µmol/L (0.57 mg/dL) with corresponding 95% limits of agreement of −179.7 to +199.2 µmol/L (−10.5 to 11.7 mg/dL). The positive predictive value of a Bilistick reading for having a total serum bilirubin level above the phototherapy threshold was 36.4%. The negative predictive value was 90.1%, sensitivity 60%, and specificity 77.6%. Hemolysis (24%) contributed to overestimations by the Bilistick. Community midwives expressed multiple barriers related to user convenience. Conclusion: Diagnostic accuracy of the Bilistick when used in the home setting was limited. Its use was further hindered by a significant proportion of failed readings and low user convenience when operated by midwives.

Background: Accurate quantification of neonatal bilirubin remains a perennial challenge. To monitor analytical performance of total bilirubin measurements across hospitals in the Netherlands, a dedicated neonatal external quality assessment (EQA) program is in place. Methods: We retrospectively analyzed Dutch EQA data from 2013 until 2025. Each year, the 81 participating laboratories received 24 pooled adult blood serum samples spiked with unconjugated bilirubin (range 100–400 µmol/L or 5.85–23.40 mg/dL). Bias from the target value determined by the reference measurement procedure (RMP) and the coefficient of variation (CV) were established for both unfactored and factored measurements. Results: In total, 25 983 bilirubin measurements were analyzed. Three analytical principles were used on 12 platforms from 6 manufacturers. Diazo-based methods exhibited the lowest median bias (+0.4% in 2024), alongside spectrophotometric methods (−3.8% in 2024). Vanadate-based methods showed a bias of +19.5% in 2024 that was reduced to +3.0% for factored measurements. Substantial differences in bias were observed among manufacturers and platforms, with some exhibiting concentration dependency. Comparable patterns were seen for CVs, which generally remained below 5%. Conclusion: EQA results demonstrated temporal variability in bias across all analytical principles, manufacturers, and platforms used for neonatal bilirubin assays. Bias was found to vary with bilirubin concentration. Standardization of neonatal bilirubin assays is urgently needed to ensure more reliable and accurate measurements across different systems. Meanwhile, EQA programs are important in monitoring future assay adjustments to ensure appropriate and consistent management of neonatal hyperbilirubinemia.