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Background Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. Methods We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). Results We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. Conclusions Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.

ObjectiveIn the Netherlands, the threshold for offering active treatment for spontaneous birth was lowered from 25+0 to 24+0 weeks’ gestation in 2010. This study aimed to evaluate the impact of guideline implementation on survival and causes and timing of death in the years following implementation.DesignNational cohort study, using data from the Netherlands Perinatal Registry.PatientsThe study population included all 3312 stillborn and live born infants with a gestational age (GA) between 240/7 and 266/7 weeks born between January 2011 and December 2017. Infants with the same GA born between January 2007 and December 2009 (N=1400) were used as the reference group.Main outcome measuresSurvival to discharge, as well as cause and timing of death.ResultsAfter guideline implementation, there was a significant increase in neonatal intensive care unit (NICU) admission rate for live born infants born at 24 weeks’ GA (27%–69%, p<0.001), resulting in increased survival to discharge in 24-week live born infants (13%–34%, p<0.001). Top three causes of in-hospital mortality were necrotising enterocolitis (28%), respiratory distress syndrome (19%) and intraventricular haemorrhage (17%). A significant decrease in cause of death either complicated or caused by respiratory insufficiency was seen over time (34% in 2011–2014 to 23% in 2015–2017, p=0.006).ConclusionsImplementation of the 2010 guideline resulted as expected in increased NICU admissions rate and postnatal survival of infants born at 24 weeks’ GA. In the years after implementation, a shift in cause of death was seen from respiratory insufficiency towards necrotising enterocolitis and sepsis.

The indications for the majority of CXRs in our PICU appeared to be in accordance with ACR guidelines. The high percentage of malpositioned tubes and lines and the number of cardiopulmonary changes on CXRs in a PICU underline the value of these films. Adjustments of the ACR guidelines for particular groups of paediatric patients may limit the number of CXRs taken and may further increase diagnostic efficacy.

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Purpose Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. Methods Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1‐1‐2010 to 31‐3‐2013 and P2: 1‐4‐2013 to 31‐12‐2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared. Results Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1‐fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 ± 1.7 versus 26.0 ± 1.7 weeks, p = 0.711), mean birth weight (791 ± 311 versus 764 ± 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born <25 weeks increased by factor 1.23 and higher oxygen saturation levels were aimed at in most centres. At treatment decision, 59.6% (P1) versus 83.5% (P2) (p = 0.263) infants were classified as Type 1 ROP (ETROP classification). Infants were treated with laser photocoagulation (98 versus 96%) and intravitreal bevacizumab (2 versus 4%). Retreatment was necessary in 10 versus 21 (p = 0.160). Retinal detachment developed in 6 versus 13 infants (p = 0.791) of which 2 versus 6 bilateral (p = 0.599). Conclusion In period 2, the number of infants treated according to the ETROP criteria (Type 1) increased, the number of ROP treatments, retinal detachments and retreatments doubled and the absolute number of retinal detachments increased. Neonatal data did not provide a decisive explanation, although changes in neonatal policy were reported.

<b><i>Introduction:</i></b> Retinopathy of prematurity (ROP) remains an important cause for preventable blindness. Aside from gestational age (GA) and birth weight, risk factor assessment can be important for determination of infants at risk of (severe) ROP. <b><i>Methods:</i></b> Prospective, multivariable risk-analysis study (NEDROP-2) was conducted, including all infants born in 2017 in the Netherlands considered eligible for ROP screening by pediatricians. Ophthalmologists provided data of screened infants, which were combined with risk factors from the national perinatal database (Perined). Clinical data and potential risk factors were compared to the first national ROP inventory (NEDROP-1, 2009). During the second period, more strict risk factor-based screening inclusion criteria were applied. <b><i>Results:</i></b> Of 1,287 eligible infants, 933 (72.5%) were screened for ROP and matched with the Perined data. Any ROP was found in 264 infants (28.3% of screened population, 2009: 21.9%) and severe ROP (sROP) (stage ≥3) in 41 infants (4.4%, 2009: 2.1%). The risk for any ROP is decreased with a higher GA (odds ratio [OR] 0.59 and 95% confidence interval [CI] 0.54–0.66) and increased for small for GA (SGA) (1.73, 1.11–2.62), mechanical ventilation &#x3e;7 days (2.13, 1.35–3.37) and postnatal corticosteroids (2.57, 1.44–4.66). For sROP, significant factors were GA (OR 0.37 and CI 0.27–0.50), SGA (OR 5.65 and CI 2.17–14.92), postnatal corticosteroids (OR 3.81 and CI 1.72–8.40), and perforated necrotizing enterocolitis (OR 7.55 and CI 2.29–24.48). <b><i>Conclusion:</i></b> In the Netherlands, sROP was diagnosed more frequently since 2009. No new risk factors for ROP were determined in the present study, apart from those already included in the current screening guideline.

This study was supported by The Thrasher Foundation (9143) to [M.S.]; The NutsOhra Foundation (1101-059) to [A.M.C.v.R.]; The Sophia Foundation for Scientific research (681) to [W.v.H.]; and the Swiss National Science Foundation (200021_188466) to [I.D.]. In addition, Thermofisher provided procalcitonin kits and provided an unrestricted grant for the organization of 4 investigator meetings (2008, 2009, 2013 and 2015). The authors have no conflicts of interest to disclose. M.S. and I.D. contributed equally as co-first authors. A.M.C.v.R. and J.E.V. contributed equally as co-senior authors.