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Data from the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) indicate that targeting a higher (91-95%) versus lower (85-89%) pulse oximeter saturation (SpO 2 ) range may reduce mortality and necrotizing enterocolitis (NEC) and increase retinopathy of prematurity (ROP). Aiming to re-evaluate the strength of this evidence, we conducted a Bayesian reanalysis of the NeOProM data. We used Bayes factors (BFs) to evaluate the likelihood of the data under the combination of models assuming the presence vs. absence of effect, heterogeneity, and moderation by sex. The Bayesian reanalysis showed moderate evidence in favor of no differences between SpO 2 targets (BF 10 = 0.30) in death or major disability, but moderate evidence (BF 10 = 3.60) in favor of a lower mortality in the higher SpO 2 group. Evidence in favor of differences was observed for bronchopulmonary dysplasia (BPD) (BF 10 = 14.44, lower rate with lower SpO 2 ), severe NEC (BF 10 = 9.94), and treated ROP (BF 10 = 3.36). The only outcome with moderate evidence in favor of sex differences was BPD. This reanalysis of the NeOProM trials confirmed that exposure to a lower versus higher SpO 2 range is associated with a higher mortality and risk of NEC, but a lower risk of ROP and BPD. The Bayesian approach can help in assessing the strength of evidence supporting clinical decisions.

Background: Retinopathy of prematurity (ROP) is generally considered to be more frequent in males than in females. However, it is not known whether sex differences in ROP affect all degrees of the condition, are global and have changed as neonatology has developed. We aimed to conduct a systematic review and meta-analysis of studies addressing sex differences in the risk of developing ROP., Methods: PubMed/MEDLINE and Embase databases were searched. The frequentist, random-effects risk ratio (RR) and 95% confidence interval (CI) were calculated. Bayesian model averaged (BMA) meta-analysis was used to calculate the Bayes factors (BFs). The BF 10 is the ratio of the probability of the data under the alternative hypothesis (H 1 ) over the probability of the data under the null hypothesis (H 0 )., Results: We included 205 studies (867,252 infants). Frequentist meta-analysis showed a positive association between male sex and severe ROP (113 studies, RR = 1.14, 95% CI = 1.07-1.22) but no association with any ROP (144 studies, RR = 1.00, 95% CI = 0.96-1.03). BMA showed extreme evidence in favor of H 1 for severe ROP (BF 10  = 71,174) and strong evidence in favor of H 0 for any ROP (BF 10  = 0.05). The association between male sex and severe ROP remained stable over time and was present only in cohorts from countries with a high or high-middle sociodemographic index., Conclusions: Our study confirms the presence of a male disadvantage in severe ROP but not in less severe forms of the disease. There are variations in the sex differences in ROP, depending on geographical location and sociodemographic level of the countries., (© 2023. The Author(s).)

Introduction: Vestibular assessment in children with sensorineural hearing loss (SNHL) is critical for early vestibular rehabilitation therapy to promote (motor) development or guide decision making towards cochlear implantation (timing of surgery and laterality). It can be challenging from a clinical viewpoint to decide which vestibular tests should be performed for a pediatric patient. The aim of this study was to evaluate the diagnostic accuracy of several clinically available vestibular tests in children with SNHL, and to provide recommendations for the implementation of vestibular testing of children in clinical practice, to screen for vestibular hypofunction (VH)., Methods: A two-center retrospective chart review was conducted. Eighty-six patients between the age of 0 and 18 years were included in this study with SNHL. Vestibular tests included video headimpulse test (VHIT), caloric test (performed at the age of four or higher), rotatory chair and cervical vestibular evoked myogenic potential (cVEMP). A combination of the clinical assessment and (combinations of) vestibular test outcomes determined the diagnosis. The diagnostic quality of tests and combination of tests was assessed by diagnostic accuracy, sensitivity and specificity., Results: VH was diagnosed in 44% of the patients. The VHIT and caloric test showed the highest diagnostic accuracy compared to the rotatory chair and cVEMP. All combinations of VHIT, caloric test and cVEMP showed improvement of the diagnostic accuracy compared to the respective tests when performed singularly. All combinations of tests showed a relatively similar diagnostic accuracy, with the VHIT combined with the caloric test scoring the highest. Adding a third test did not substantially improve the diagnostic accuracy., Discussion: Vestibular testing is feasible and VH is highly prevalent in children with SNHL. A proposed diagnostic algorithm recommends starting with VHIT, followed by cVEMP for children under the age of four, and caloric testing for older children if VH is not confirmed with the first test. Performing a third test is redundant as the diagnostic accuracy does not improve substantially. However, challenges remain, including the lack of a gold standard and the subjective nature of the diagnosis, highlighting the need for standardized testing and increased understanding of VH in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Gerdsen, Hundscheid, Boudewyns, Van Rompaey, Van De Berg and Widdershoven.)

Introduction: Antenatal antibiotic exposure has been suggested as a risk factor for bronchopulmonary dysplasia (BPD). We aimed to summarize the evidence from randomized controlled trials (RCTs) and observational studies on this potential association., Methods: PubMed/Medline and Embase databases were searched. BPD was classified as BPD28 (supplemental oxygen during 28 days or at postnatal day 28), BPD36 (supplemental oxygen at 36 weeks postmenstrual age), BPD36 or death, and BPD-associated pulmonary hypertension (BPD-PH). Bayesian model-averaged (BMA) meta-analysis was used to calculate Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (H1) over the probability of the data under the null hypothesis (H0)., Results: We included 6 RCTs and 27 observational studies (126,614 infants). Regarding BPD28, BMA showed that the evidence in favor of H0 (lack of association with antenatal antibiotics) was weak for the RCTS (BF10 = 0.506, 6 studies) and moderate for the observational studies (BF10 = 0.286, 10 studies). Regarding BPD36, the evidence in favor of H0 was moderate for the RCTs (BF10 = 0.127, 2 studies) and weak for the observational studies (BF10 = 0.895, 14 studies). Evidence in favor of H0 was also weak for the associations with BPD36 or death (BF10 = 0.429, 2 studies) and BPD-PH (BF10 = 0.384, 2 studies). None of the meta-analyses showed evidence in favor of H1., Conclusions: The currently available evidence suggests a lack of association between antenatal antibiotics and BPD. However, our results should not be interpreted as an argument for widespread use of antibiotics in the setting of preterm delivery., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: We aimed to conduct a systematic review and Bayesian model-averaged meta-analysis (BMA) on the association between platelet counts and severe retinopathy of prematurity (ROP)., Methods: We searched for studies reporting on platelet counts (continuous variable) or thrombocytopenia (categorical variable) and severe ROP or aggressive posterior ROP (APROP). The timing of platelet counts was divided into Phase 1 (<2 weeks) and Phase 2 (around ROP treatment). BMA was used to calculate Bayes factors (BFs). The BF 10 is the ratio of the probability of the data under the alternative hypothesis (H 1 ) over the probability of the data under the null hypothesis (H 0 )., Results: We included 21 studies. BMA showed an association between low platelet counts and severe ROP. The evidence was strong (BF 10 = 13.5, 7 studies) for phase 1 and very strong (BF 10 = 51.0, 9 studies) for phase 2. Thrombocytopenia (<100 × 10 9 /L) in phase 2 was associated with severe ROP (BF 10 = 28.2, 4 studies). Following adjustment for publication bias, only the association of severe ROP with thrombocytopenia remained with moderate evidence in favor of H 1 (BF 10 = 4.30)., Conclusions: Thrombocytopenia is associated with severe ROP. However, the evidence for this association was tempered when results were adjusted for publication bias.

The fetal systemic inflammatory response associated with intra-amniotic inflammation may play a key role in the pathogenesis of complications of preterm birth. Funisitis is the histologic equivalent of the fetal inflammatory response, whereas chorioamnionitis represents a maternal inflammatory response. We conducted a frequentist and Bayesian model average (BMA) meta-analysis of studies investigating the effects of funisitis on short-term outcomes of prematurity. Thirty-three studies (12,237 infants with gestational age ≤ 34 weeks) were included. Frequentist meta-analysis showed that funisitis was associated with an increased risk of any bronchopulmonary dysplasia (BPD), moderate/severe BPD, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), any sepsis, early-onset sepsis (EOS), and mortality. However, Bayesian meta-analysis showed that the evidence in favor of the alternative hypothesis (i.e., funisitis is associated with an increased risk of developing the outcome) was strong for any IVH, moderate for severe IVH and EOS, and weak for the other outcomes. When the control group was restricted to infants having chorioamnionitis without funisitis, the only outcome associated with funisitis was any IVH. In conclusion, our data suggest that the presence of funisitis does not add an additional risk to preterm birth when compared to chorioamnionitis in the absence of fetal inflammatory response.

Introduction: Preterm birth represents the leading cause of neonatal mortality. Pathophysiological pathways, or endotypes, leading to prematurity can be clustered into infection/inflammation and dysfunctional placentation. We aimed to perform a systematic review and meta-analysis exploring the association between these endotypes and risk of mortality during first hospital admission Methods: PROSPERO ID: CRD42020184843. PubMed and Embase were searched for observational studies examining infants with gestational age (GA) ≤34 weeks. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDP) and small for GA (SGA)/intrauterine growth restriction (IUGR). A random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals. Heterogeneity was studied using random-effects meta-regression analysis., Results: Of 4,322 potentially relevant studies, 150 (612,580 infants) were included. Meta-analysis showed positive mortality odds for chorioamnionitis (OR: 1.43, 95% confidence interval: 1.25-1.62) and SGA/IUGR (OR: 1.68, 95% confidence interval: 1.38-2.04) but negative mortality odds for HDP (OR 0.74, 95% confidence interval: 0.64-0.86). Chorioamnionitis was associated with a lower GA, while HDP and SGA/IUGR were associated with a higher GA. Meta-regression showed a significant correlation between these differences in GA and mortality odds., Conclusion: Our data suggest that the infectious/inflammatory endotype of prematurity has a greater overall impact on mortality risk as it is the most frequent endotype in the lower GAs. However, when the endotype of placental dysfunction is severe enough to induce growth restriction, it is strongly associated with higher mortality rates even though newborns are more mature., (© 2023 The Author(s). Published by S. Karger AG, Basel.)