Association between Antenatal Antibiotic Exposure and Bronchopulmonary Dysplasia: A Systematic Review and Bayesian Model-Averaged Meta-Analysis.

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.

Platelet Counts and Risk of Severe Retinopathy of Prematurity: A Bayesian Model-Averaged Meta-Analysis.

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 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 21 studies. BMA showed an association between low platelet counts and severe ROP. The evidence was strong (BF10 = 13.5, 7 studies) for phase 1 and very strong (BF10 = 51.0, 9 studies) for phase 2. Thrombocytopenia (<100 × 109/L) in phase 2 was associated with severe ROP (BF10 = 28.2, 4 studies). Following adjustment for publication bias, only the association of severe ROP with thrombocytopenia remained with moderate evidence in favor of H1 (BF10 = 4.30). CONCLUSIONS: Thrombocytopenia is associated with severe ROP. However, the evidence for this association was tempered when results were adjusted for publication bias.

Sex differences in the risk of retinopathy of prematurity: a systematic review, frequentist and Bayesian meta-analysis, and meta-regression.

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 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 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 H1 for severe ROP (BF10 = 71,174) and strong evidence in favor of H0 for any ROP (BF10 = 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.

Association between Endotype of Prematurity and Mortality: A Systematic Review, Meta-Analysis, and Meta-Regression.

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.