What happens when the patent ductus arteriosus is treated less aggressively in very low birth weight infants?

OBJECTIVE: It remains unclear whether indomethacin (INDO) and/or surgical ligation (LIGATE) are necessary to improve outcomes in premature infants with a patent ductus arteriosus (PDA). We have adopted a conservative approach to PDA management that emphasizes waiting for spontaneous closure unless certain cardiorespiratory distress criteria are met. STUDY DESIGN: This was a before-after observational study in infants born 501 to 1,500 g in two distinct epochs. Era 1 (January 2005 to December 2007) featured traditional management with INDO and LIGATE used early to close all moderate and large PDAs in infants receiving any respiratory support. Era 2 (January 2008 to June 2009) emphasized modest fluid restriction, watchful waiting and limited INDO and LIGATE to only those infants with large PDAs who met certain cardiorespiratory distress criteria. RESULT: Era 1 included 139 infants with a PDA, mean (s.d.) gestational age 27.5 (2) weeks; Era 2 72 infants, mean (s.d.) gestational age 27.5 (2) weeks. In Era 2, INDO use significantly decreased (79% of infants to 26%, P<0.001), and 28 day total fluids decreased (140 vs. 130 ml kg(-1) day(-1), P<0.001). LIGATE rate was 45% in Era 1, 33% in Era 2 (P=0.11). There were no significant differences in supplemental oxygen, nasal continuous positive airway pressure, or mechanical ventilation days. There were no significant differences in mortality or individual morbidities. The combined outcome of chronic lung disease (CLD) or mortality after Day 7 significantly increased (Era 1, 40%, Era 2, 54%, P=0.04). More infants were discharged home with a PDA in Era 2, but most resolved spontaneously and the need for closure therapy after discharge from the neonatal intensive care unit (NICU) did not increase. Multiple regression analysis demonstrated Era 2 management did not predict an increased risk of one or more interlinked morbidities. CONCLUSION: Tolerance of the PDA with watchful waiting for spontaneous closure, modest fluid reduction, and less INDO use is a reasonable treatment strategy that is not associated with significant changes in NICU mortality or individual morbidities. We did note an increase in the combined outcome of CLD or mortality after Day 7, thus our investigation supports the urgency of a randomized controlled trial comparing traditional PDA management with a true control group similar to our Era 2 management to answer important questions of short and long-term outcomes.

Hyperglycemia, insulin and slower growth velocity may increase the risk of retinopathy of prematurity.

OBJECTIVE: Strategies to reduce Retinopathy of Prematurity (ROP) have focused primarily on respiratory management. Hyperglycemia (HG) and insulin use, risk factors for adult diabetic retinopathy, as well as growth rates may be modifiable variables useful to reduce ROP. STUDY DESIGN: This was a retrospective chart review of all infants born at <30 weeks gestation from 2003 to 2007 who survived to discharge in our neonatal intensive care unit (NICU). All whole-blood glucose values (BG in mg dl(-1)) done in the first 29 days of life were collected for analysis. RESULT: BGs were done at least every 3 to 6 h for the first 48 to 96 h of life, then every 6 to 24 h thereafter, as long as infants remained on hyperalimentation. Hyperglycemia was defined as mild (BG 151 to 180), moderate (181 to 210) or severe (>210). Insulin use (given if BG>180 to 210) was also noted for each simultaneous BG. ROP was classified as none, mild (stage 1 to 2) or severe (stage 3 to 4). Growth velocity (g kg(-1) per day), length and head circumference were also analyzed. In all, 372 infants mean (s.d.) gestational age 27.6 (1.4) weeks, mean (s.d.) birth weight 994 (242)g had 18,649 BGs analyzed. 103 (28%) of the infants had mild ROP and 29 (8%) had severe ROP. 137 (37%) of the infants received at least 1 day of exogenous insulin (median days 9, range 1 to 26). Higher cumulative mean BG, more episodes of HG, and more insulin exposure were associated with an increased incidence and severity of ROP. Ordinal logistic regression identified lower gestational age, male gender, fetal growth restriction, slower NICU growth velocity, and higher BG as predictors for severity of ROP. However, insulin use was a stronger predictor than BG, and replaced it in the risk model. CONCLUSION: After adjusting for important risk factors, HG and especially insulin use in premature infants may increase the risk of ROP. In addition, slower NICU growth velocity, but not rates of head or length growth, was predictive of ROP.