BackgroundFetal and neonatal exposure to antibiotics may contribute to the development of necrotizing enterocolitis (NEC) in preterm infants. This systematic review and meta-analysis investigate whether exposure to third trimester maternal antibiotics (MAB) and/or prolongation of empirical antibiotics (PEAB) are associated with NEC development in preterms.MethodWe included observational and randomized controlled studies, including those on preterm or very low birth weight (VLBW) infants, from MEDLINE and EMBASE, published between 1990 and June 2021. Exposure was defined as third trimester MAB and/or PEAB. The two reviewers independently performed study selection, data extraction, and quality assessment.ResultsThree cohort studies compared third trimester MAB with no antibiotics. MAB was associated with lower NEC incidence, unadjusted pooled odds ratio (OR) is 0.57 (95% CI: 0.35–0.93). Twelve cohort studies showed that PEAB was associated with an increased risk of NEC. Ten observational cohort studies show an unadjusted OR of 2.72 (1.65–4.47), and two case–control studies show an unadjusted mean difference of 2.31 (0.94–3.68). Moderate to substantial heterogeneity was observed but decreased in studies with low risk of bias and large sample size.ConclusionEvidence suggests an association between MAB and decreased risk of NEC and an association between PEAB and increased risk of NEC. Further studies should confirm these associations and explore causality.Systematic Review Registrationidentifier [CRD42022304937].

Background. Patients with curable esophageal cancer (EC) who proceed beyond the original Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect that extending the CROSS eligibility criteria for nCRT has on treatment-related toxicity and overall survival (OS) in EC. Methods. The study enrolled 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0) treated with the CROSS schedule followed by esophagectomy. Group 1 consisted of 89 patients who met the CROSS criteria, and group 2 consisted of 72 patients who met the extended eligibility criteria, i.e. a tumor length greater than 8 cm (n = 24), more than 10% weight loss (n = 35), more than 2-4 cm extension in the stomach (n = 21), celiac lymph node metastasis (n = 13), and/or age over 75 years (n = 2). The study assessed the differences in nCRT-associated toxicity [National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) grade C 3] and 90-day postoperative mortality. Moreover, the prognostic value for OS was assessed with multivariate Cox regression analysis. Results. No difference was found in nCRT-associated toxicity (P = 0.117), postoperative complications (P = 0.783), and 90-day mortality (P = 0.492). The OS differed significantly (P = 0.004), with a median of 37.3 months [95% confidence interval (CI), 10.4-64.2 months] for group 1 and 17.2 months (95% CI 13.8-20.7 months) for group 2. Pathologic N stage (P = 0.023), pathologic T stage (P = 0.043), and group 2 (P = 0.008) were independent prognostic factors for OS. Conclusions. Extension of the CROSS study eligibility criteria for nCRT did not affect nCRT-associated toxicity, postoperative complications, and postoperative mortality, but was prognostic for OS.Neoadjuvant chemoradiotherapy (nCRT) according to the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) schedule (carboplatin/paclitaxel and 41.4 Gy radiotherapy) followed by a radical surgical resection is the gold standard for locally advanced esophageal cancer (EC) in the Netherlands.1 This nCRT scheme increased the 5-year overall survival (OS) by 10-13% while the postoperative complication rate did not increase.