BackgroundThe developmental origin of health and disease concept identifies the brain, cardiovascular, liver, and kidney systems as targets of fetal adverse programming with adult consequences. As the limits of viability in premature infants have been pushed to lower gestational ages, the long-term impact of prematurity on kidneys still remains a significant burden during hospital stay and beyond.ObjectivesThe purpose of this study is to summarize available evidence, mechanisms, and short- and long-term renal consequences of prematurity and identify nephroprotective strategies and areas of uncertainty.ResultsKidney size and nephron number are known to be reduced in surviving premature infants due to disruption of organogenesis at a crucial developmental time point. Inflammation, hyperoxia, and antiangiogenic factors play a role in epigenetic conditioning with potential life-long consequences. Additional kidney injury from hypoperfusion and nephrotoxicity results in structural and functional changes over time which are often unnoticed. Nephropathy of prematurity and acute kidney injury confound glomerular and tubular maturation of preterm kidneys. Kidney protective strategies may ameliorate growth failure and suboptimal neurodevelopmental outcomes in the short term. In later life, subclinical chronic renal disease may progress, even in asymptomatic survivors.ConclusionAwareness of renal implications of therapeutic interventions and renal conservation efforts may lead to a variety of short and long-term benefits. Adequate monitoring and supplementation of microelement losses, gathering improved data on renal handling, and exploration of new avenues such as reliable markers of injury and new therapeutic strategies in contemporary populations, as well as long-term follow-up of renal function, is warranted.

Exposure to transfusion in previous 2 days was an independent risk factor for NEC. After controlling for confounders, no significant differences in mortality and morbidities were observed between infants who had transfusion-associated NEC and those with NEC not associated with transfusion.

BackgroundThere are conflicting results in the literature on the impact of chorioamnionitis on neonatal respiratory morbidities. However, most studies are based on small clinical samples and fail to account for the competing risk of perinatal death. This study aimed to determine whether chorioamnionitis affects the incidence of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) after accounting for the increased risk of death.MethodsRetrospective cohort study using linked birth and infant death registration and hospitalization records from Washington State between 2002 and 2011 (n = 763,671 singleton infants and n = 56,537 singleton preterm infants). Logistic regression models based on the traditional and fetuses-at-risk approaches were used to model two composite outcomes namely RDS and perinatal death and BPD and perinatal death. Confounders adjusted for in the models included maternal age, race, diabetes, hypertension, antenatal corticosteroids, mode of delivery and infant sex.ResultsWhile models using the traditional approach found a significant association only between chorioamnionitis and composite BPD and perinatal death (OR = 1.23, 95% CI: 1.01–1.50); using the fetuses-at-risk approach, there was a significant association between chorioamnionitis and both composite outcomes (RDS and perinatal death OR = 2.74, 2.50–3.01; BPD and perinatal death OR = 5.18, 95% CI: 4.39–6.11).ConclusionThe fetuses-at-risk approach models the causal impact of chorioamnionitis on the development of the fetal lung and shows an increased risk of RDS, BPD and perinatal death associated with such maternal infection.

Objective: To evaluate the prevalence, risk factors, and optimal timing of echocardiogram for pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD).Design: In this prospective study, infants with gestational age (GA) <30 weeks admitted to a tertiary NICU between July 2015 and June 2017 who required positive pressure ventilation or oxygen therapy at ≥28 days of life were evaluated with serial echocardiograms at study enrollment (4-6 weeks of age), 32 weeks (only for ≤25 weeks), 36, and 40 weeks post-menstrual age (PMA) for PH.Results: Of 126 infants (mean birth weight 858 ± 221 g; mean GA 26.1 ± 1.6 wks), 48 (38%) developed PH at any time during their hospital stay. The first study echocardiogram was performed at a median age of 31 weeks PMA. The prevalence of PH was 36/126 (28.5%) at enrollment, at 6/30 (20%) at 32 weeks, 24/111 (21.6%) at 36 weeks, and 10/ 59 (17%) at 40 weeks. No new cases of PH were identified at 40 weeks. At 36 weeks, none of the infants with mild BPD had PH, whereas 20% of moderate and 32% of severe BPD infants had PH. After controlling for confounding variables severe BPD (OR 3.31, 95%CI 1.12, 9.74), and ventilator associated pneumonia (VAP) (OR 17.9, 95%CI 3.9, 82.11) remained independent risk factors for BPD-associated PH.Conclusion: Echocardiographic screening for PH can be safely restricted to infants with moderate or severe BPD at 36 weeks PMA. We identified VAP as an independent risk factor for PH. K E Y W O R D Sbronchopulmonary dysplasia, preterm, pulmonary hypertension, ventilator associated pneumonia Abbreviations: ASD, atrial septal defect; BPD, bronchopulmonary dysplasia; BW, birth weight; EI, eccentricity index; GA, gestational age; iNO, inhaled nitric oxide; IVH, intraventricular hemorrhage; LVEF, left ventricular ejection fraction; NEC, necrotizing enterocolitis; NICU, neonatal intensive care unit; PDA, patent ductus arteriosus; PFO, patent foramen ovale; PH, pulmonary hypertension; PMA, postmenstrual age; ROP, retinopathy of prematurity; RV, right ventricle; RVSP, right ventricular systolic pressure; SD, standard deviation; SNAP-II, score of neonatal acute physiology-version II; TAPSE, tricuspid annular plane systolic excursion; VAP, ventilator associated pneumonia.

Objectives: To assess maternal and neonatal risk factors for intraventricular hemorrhage (IVH). To examine the association of patent ductus arteriosus (PDA) and its treatment, with IVH and its severity.Study design: In this retrospective cohort study, we included preterm neonates born at <29 weeks, admitted to a tertiary level III Neonatal Intensive Care Unit in Calgary, Canada, between 2013 and 2016, who had a head ultrasound in the first 7 days of life. A subset analysis included neonates who also had cardiac ultrasound in the first 3 days of life.Results: Of the 495 neonates, 121 (24.4%) had IVH of any grade and 48 (9.7%) had severe IVH. Identified risk factors were small birth gestation and weight, lack of antenatal corticosteroids, maternal chorioamnionitis, Apgar score <5 at 5 min, umbilical cord pH < 7, respiratory distress syndrome, early onset sepsis, hypercapnia, pCO2 fluctuations, prolonged intubation, inhaled nitric oxide, inotropes or normal saline boluses, metabolic derangements, opioids infusions, and bicarbonate/THAM therapy. In a primary analysis of the total cohort, when the decision to treat a PDA was used as a surrogate marker of its clinical significance, a PDA requiring treatment was associated with a higher risk of IVH. There was no significant difference in the incidence of IVH between neonates with early treatment of a clinically significant PDA compared to late, however early indomethacin treatment was associated with reduced severity of IVH. In the subset analysis, the presence of a hemodynamically significant PDA (hs-PDA) was not associated with a higher probability of IVH. Of those with severe IVH, 18 (55%) had a hs-PDA; this is clinically but not statistically significant.Conclusions: Identified risk factors should be the target of IVH reduction bundles. Early indomethacin treatment for a clinically significant PDA may reduce IVH severity.