High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity.

OBJECTIVE: Symptomatic patent ductus arteriosus (sPDA) is the most common heart abnormality in preterm infants. Optimal duration and dose of medical treatment is still unclear. We assessed undesired effects and closure rate of high-dose indomethacin (HDI) for pharmacological closure of sPDA. STUDY DESIGN: Retrospective single center analysis of 248 preterm infants born between January 2006 and December 2015 with a birth weight <2,000 g and sPDA which was treated with indomethacin. Patients were treated with either standard dose indomethacin (SDI; n = 196) or HDI (n = 52). Undesired effects and PDA closure were compared between patients treated with SDI and HDI. RESULTS: In univariate analysis, patients receiving HDI had a significant increase in gastrointestinal hemorrhage (32.7 vs.11.7%, p = 0.001), bronchopulmonary dysplasia (BPD) (77.8 vs. 55.1%, p = 0.003), and retinopathy of prematurity (13.5 vs. 2.6%, p = 0.004). Moreover, HDI patients needed longer mechanical ventilation (2.5 vs. 1.0 days, p = 0.01). Multivariate analyses indicated that necrotizing enterocolitis (17 vs. 7%, p = 0.01) and BPD (79 vs. 55%, p = 0.02) were more frequent in HDI patients. PDA closure rate was 79.0% with HDI versus 65.3% with SDI. CONCLUSION: HDI used for PDA closure is associated with an increase in necrotizing enterocolitis and BPD. Risks of HDI should be balanced against other treatment options.

Intravitreal ranibizumab monotherapy to treat retinopathy of prematurity zone II, stage 3 with plus disease.

BACKGROUND: Treatment of retinopathy of prematurity (ROP) stage 3 plus with bevacizumab is still very controversial. We report the outcome of 6 eyes of 4 premature infants with ROP stage 3 plus disease treated with ranibizumab monotherapy. METHODS: Six eyes of 4 premature infants with threshold ROP 3 plus disease in zone II, were treated with one intravitreal injection of 0.03 ml ranibizumab. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow-up visit. Changes in various mean vital parameters one week post intervention compared to one week pre-intervention were assessed. RESULTS: The gestational age (GA) of patient 1, 2, 3, and 4 at birth was 24 5/7, 24 5/7, 24 4/7, and 26 1/7 weeks, respectively. The birth weight was 500 grams, 450 grams, 665 grams, and 745 grams, respectively. The GA at the date of treatment ranged from 34 3/7 to 38 6/7 weeks. In one infant, upper air way infection was observed 2 days post injection of the second eye. Three eyes required paracentesis to reduce the intraocular pressure after injection and to restore central artery perfusion. After six months, all eyes showed complete retinal vascularisation without any signs of disease recurrence. CONCLUSIONS: Treatment of ROP 3 plus disease with intravitreal ranibizumab was effective in all cases and should be considered for treatment. One infant developed an upper air way infection suspicious for nasopharyngitis, which might be a possible side effect of ranibizumab. Another frequent complication was intraocular pressure rise after injection. More patients with longer follow-up duration are mandatory to confirm the safety and efficacy of this treatment. TRIAL REGISTRATION NUMBER: NCT02164604; Date of registration: 13.06.2014.