The role of chorioamnionitis (CA) in the development of retinopathy of prematurity (ROP) is difficult to establish, because CA-exposed and CA-unexposed infants frequently present different baseline characteristics. We performed an updated systematic review and meta-analysis of studies reporting on the association between CA and ROP. We searched PubMed and EMBASE for relevant articles. Studies were included if they examined preterm or very low birth weight (VLBW, <1500g) infants and reported primary data that could be used to measure the association between exposure to CA and the presence of ROP. Of 748 potentially relevant studies, 50 studies met the inclusion criteria (38,986 infants, 9,258 CA cases). Meta-analysis showed a significant positive association between CA and any stage ROP (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.11 to 1.74). CA was also associated with severe (stage ≥3) ROP (OR 1.63, 95% CI 1.41 to 1.89). Exposure to funisitis was associated with a higher risk of ROP than exposure to CA in the absence of funisitis. Additional meta-analyses showed that infants exposed to CA had lower gestational age (GA) and lower birth weight (BW). Meta-regression showed that lower GA and BW in the CA-exposed group was significantly associated with a higher risk of ROP. Meta-analyses of studies with data adjusted for confounders could not find a significant association between CA and ROP. In conclusion, our study confirms that CA is a risk factor for developing ROP. However, part of the effects of CA on the pathogenesis of ROP may be mediated by the role of CA as an etiological factor for very preterm birth.

In recent years, magnetic resonance imaging (MRI) has largely increased our knowledge and predictive accuracy of congenital diaphragmatic hernia (CDH) in the fetus. Thanks to its technical advantages, better anatomical definition, and superiority in fetal lung volume estimation, fetal MRI has been demonstrated to be superior to 2D and 3D ultrasound alone in CDH diagnosis and outcome prediction. This is of crucial importance for prenatal counseling, risk stratification, and decision-making approach. Furthermore, several quantitative and qualitative parameters can be evaluated simultaneously, which have been associated with survival, postnatal course severity, and long-term morbidity.Conclusion: Fetal MRI will further strengthen its role in the near future, but it is necessary to reach a consensus on indications, methodology, and data interpretation. In addition, it is required data integration from different imaging modalities and clinical courses, especially for predicting postnatal pulmonary hypertension. This would lead to a comprehensive prognostic assessment. What is Known:• MRI plays a key role in evaluating the fetal lung in patients with CDH.• Prognostic assessment of CDH is challenging, and advanced imaging is crucial for a complete prenatal assessment and counseling. What is New:• Fetal MRI has strengthened its role over ultrasound due to its technical advantages, better anatomical definition, superior fetal lung volume estimation, and outcome prediction.• Imaging and clinical data integration is the most desirable strategy and may provide new MRI applications and future research opportunities.

Fresh frozen plasma (FFP) is largely misused in the neonatal setting. The aim of the study is to evaluate the impact of a Thromboelastography (TEG)-based Quality Improvement (QI) project on perioperative FFP use and neonatal outcomes. Retrospective pre-post implementation study in a level-III NICU including all neonates undergoing major non-cardiac surgery before (01–12/2017) and after (01–12/2019) the intervention. In 2018, the intervention included the following: (1) Training on TEG, (2) Implementation of TEG, and (3) Algorithm for TEG-directed FFP administration in surgical neonates. We compared pre- vs post-intervention patient characteristics, hemostasis, and clinical management. Linear and logistic regression models were used to evaluate the impact of the project on main outcomes. We analyzed 139 neonates (pre-intervention: 72/post-intervention: 67) with a mean (± SD) gestational age (GA) 34.9 (± 5) weeks and birthweight 2265 (± 980) grams which were exposed to 184 surgical procedures (pre-intervention: 91/post-intervention: 93). Baseline characteristics were similar between periods. In 2019, prothrombin time (PT) was longer (14.3 vs 13.2 s; p < 0.05) and fibrinogen was lower (229 vs 265 mg/dl; p < 0.05), if compared to 2017. In 2019, the intraoperative exposure to FFP decreased (31% vs 60%, p < 0.001), while the pre-operative FFP use did not change. The reduction of intraoperative FFP did not impact on mortality and morbidity. Intraoperative FFP use was lower in the post-intervention even after controlling for GA, American Society of Anesthesiologists score, PT, and fibrinogen (Odds ratio: 0.167; 95% CI: 0.070, 0.371).   Conclusion: The TEG-based QI project for the management of FFP during neonatal surgery reduced intraoperative FFP exposure. What is Known:• PT and aPTT are poor predictors of bleeding risk in acquired neonatal coagulopathy, leading to likely unnecessary fresh frozen plasma (FFP) transfusion in the Neonatal Intensive Care Setting. • As neonatal hemostasis is a delicate balance between the concomitant reduction of pro- and anti-coagulants drivers, thromboelastography (TEG) is a promising alternative for coagulation monitoring. What is New:• The implementation of TEG, training, and shared protocols contributed to reduced intraoperative FFP use, which was not associated with increased mortality or bleeding events.• These findings inform future research showing that there is clinical equipoise to allow for larger studies to confirm the use of TEG in NICUs and to identify TEG cut-offs for transfusion practice.

Congenital hemolytic anemias (CHAs) are a group of diseases characterized by premature destruction of erythrocytes as a consequence of intrinsic red blood cells abnormalities. Suggestive features of CHAs are anemia and hemolysis, with high reticulocyte count, unconjugated hyperbilirubinemia, increased lactate dehydrogenase (LDH), and reduced haptoglobin. The peripheral blood smear can help the differential diagnosis. In this review, we discuss the clinical management of severe CHAs presenting early on in the neonatal period. Appropriate knowledge and a high index of suspicion are crucial for a timely differential diagnosis and management. Here, we provide an overview of the most common conditions, such as glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and hereditary spherocytosis. Although rare, congenital dyserythropoietic anemias are included as they may be suspected in early life, while hemoglobinopathies will not be discussed, as they usually manifest at a later age, when fetal hemoglobin (HbF) is replaced by the adult form (HbA).

Background: The role of hemostasis in the closure of patent ductus arteriosus (PDA) in preterm infants is controversial. Objective: To assess thromboelastography (TEG) at birth in very-low-birth-weight (VLBW) infants affected by PDA. Methods: This was an ancillary study of a prospective observational study aimed at defining the TEG profile in healthy VLBW infants in the first month of life. In this analysis, we included neonates of <33 weeks’ gestational age (GA) with PDA and compared TEG traces based on (1) spontaneous closure versus the need for pharmacological treatment and (2) treatment response. We collected blood samples in the 1st day of life to perform recalcified native-blood TEG (reaction time, maximum amplitude, and lysis at 30 min [Ly30)]), standard coagulation tests, and a full blood count. Results: We enrolled 151 infants with a PDA at the first echocardiogram; 111 experienced spontaneous PDA closure while 40 required treatment. Mean GA was 29.7 ± 1.7 and 27.6 ± 2.1 weeks, and birth weight was 1,158 ± 256 and 933 ± 263 g in the 2 groups, respectively (p < 0.001). The hemostatic profile was similar between groups. Median hematocrit (44.6 and 48.7%; p = 0.01) and platelet count (187 and 216 × 10³/μL; p = 0.04) were lower in the treated group, although differences lost significance after controlling for GA and illness severity in the multivariate analysis. Responders to PDA treatment (n = 20) had a significantly lower median Ly30 than nonresponders (0 and 0.7%; p = 0.02). Conclusion: TEG at birth does not predict spontaneous PDA closure in preterm newborns. Fibrinolysis is enhanced in nonresponders to PDA treatment; this observation warrants further investigation.

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3–6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 10⁶ or 1 × 10⁶) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 10⁶) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.