Preterm infants are at increased risk for patent ductus arteriosus (PDA). Prolonged exposure to PDA may be deleterious and has been associated with neonatal morbidity and mortality. Although the molecular mechanisms underlying regulation of postnatal ductus arteriosus closure are not fully understood, clinical experience and research trials have informed recent changes in PDA management strategies and refocused treatment strategies on smaller subsets of infants who require intervention. This review examines current diagnostic and management approaches to PDA in preterm neonates.

Objective To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. Study design We performed a multicenter study of infants born at <32 weeks gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured three times: before and after a cosyntropin (1.0 microgram/kg) stimulation test (performed prior to the ligation), and at 10–12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified Inotrope Score (1 x dopamine (μg/kg/min) + 1 x dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their highest Inotrope Score was >15. Results Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low post-operative cortisol levels were not associated with the overall incidence of hypotension following ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the odds ratio for developing catecholamine-resistant hypotension was OR=36.6, CI=2.8–476, p=0.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not due to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Conclusion Infants with low cortisol concentrations following PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production.

Objective To test the hypothesis that infants who are just being introduced to enteral feedings will advance to full enteral nutrition at a faster rate if they receive “trophic” (15 ml/kg/day) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus (PDA). Study design Infants were eligible for the study if they were 231/7 – 306/7 weeks gestation, weighed 401–1250 g at birth, received maximum enteral volumes ≤60 ml/kg/day and were about to be treated with indomethacin or ibuprofen. A standardized “feeding advance regimen” and guidelines for managing feeding intolerance were followed at each site (n=13). Results Infants (n=177; 26.3±1.9 wks (±SD) gestation) were randomized at 6.5±3.9 days to receive “trophic” feeds (“feeding” group, n=81: indomethacin=80%, ibuprofen=20%) or no feeds (“fasting (npo)” group, n=96: indomethacin=75%, ibuprofen=25%) during the drug administration period. Maximum daily enteral volumes prior to study entry were 14±15 ml/kg/day. After drug treatment, infants randomized to the “feeding” arm required fewer days to reach the study’s feeding volume endpoint (120 ml/kg/day). Although the enteral feeding endpoint was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the two groups. There were no differences between the two groups in the incidence of infection, necrotizing enterocolitis, spontaneous intestinal perforation or other neonatal morbidities. Conclusion Infants required less time to reach the feeding volume endpoint if they were given “trophic” enteral feedings when they received indomethacin or ibuprofen treatments.

Objective Near-infrared spectroscopy (NIRS) is used to monitor brain and kidney perfusion in at-risk premature and term neonates. Although NIRS holds potential for bedside monitoring of intestinal perfusion, there is insufficient evidence showing correlation with mesenteric blood flow. To determine if an association exists between abdominal regional oxygen saturation (A-rSO2) and mesenteric blood flow, we compared changes in A-rSO2 to changes in blood flow velocity in the superior mesenteric artery (SMA) before and after feedings in very-low birthweight infants. Study Design A-rSO2 was continuously monitored midline below the umbilicus for 3 days in 18 stable 25–31 week bolus-fed infants (median BW 1203g, median age 5 days). We compared change in SMA velocity from immediately before to 10 minutes and 60–120 minutes after feeding with change in A-rSO2 over the same time. Spearman’s rank correlation was used to ascertain if a significant association existed. Result Change in A-rSO2 was significantly associated with change in systolic, diastolic, and mean SMA velocity from fasting to 60–120 minutes after feeding (p=0.016, 0.021, 0.010) and from 10 minutes after a feed to 60–120 minutes after feeding (p=0.009, 0.035, 0.032). Conclusion In very preterm infants, A-rSO2 reflects blood flow in the SMA and can provide non-invasive continuous monitoring of intestinal perfusion. Further studies are indicated to determine the sensitivity of NIRS to detect early intestinal pathology in this population.

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Objective We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine if echocardiographic indices of impaired myocardial performance were associated with subsequent development of catecholamine-resistant hypotension following ligation. Study Design A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was >15 µg/kg/min. Echocardiograms and cortisol measurements were obtained between 6 and 14 hours after the ligation (prior to the presence of catecholamine-resistant hypotension). Results 45 infants were enrolled: 10 received catecholamines (6 were catecholamine-responsive, 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration. Conclusion We speculate that low cortisol levels and impaired vascular tone may play a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension.