Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury

Cerebral Oxygenation and Metabolism After Hypoxia-Ischemia

“…Indomethacin is effective in closing PDAs; however, an RCT in preterm infants showed that a high dose of indomethacin was associated with a significant reduction in cerebral blood flow and oxygen delivery ( 85 ). This is of concern since, despite conflicting evidence, prophylactic indomethacin is administered inconsistently but relatively commonly to extremely preterm infants to promote PDA closure and ultimately to improve cerebral perfusion ( 86 ). Further, an observational study in very preterm infants showed that prophylactic indomethacin treatment was associated with a mild but significant increase in cerebral oxygen extraction, denoting reduced cerebral blood flow ( 87 ).…”

Indomethacin Prophylaxis in Preterm Infants: Changes over Time

“…Subsequent cohort studies indicate that clinicians at many centers have continued to use prophylactic indomethacin for extremely preterm infants [17][18][19] . Use of prophylactic indomethacin in extremely preterm infants is highly variable due to its potential benefits and risks [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] .…”

“…case-control analysis of 47 neonates 33 . Continued monitoring of use of prophylactic indomethacin is warranted given recent recommendations from ACOG regarding dosing of antenatal steroids for infants < 24 weeks gestation 18,19,34,35 . Retrospective cohort studies of interactions between antenatal steroid dosing and use of postnatal indomethacin in the first postnatal days show a perplexing mix of risk and benefit which warrants ongoing study 18,19 .…”

Neonatal Network Data Based‒Associations Based on Large Numbers that May Be Spurious

“…T wo reports in the current volume of The Journal use large data sets from the Canadian Neonatal Network to ask questions about postnatal indomethacin exposures and spontaneous intestinal perforation (SIP) and gestational age variations in neonatal outcomes from postnatal indomethacin such as early death. 1,2 Qureshi et al specifically questioned whether antenatal steroid use influenced the incidence of SIP with postnatal indomethacin use, as suggested by Shah et al 1 Both studies suffer from the same weakness-the infrequent and idiosyncratic use of postnatal indomethacin across the network sites-variable use within sites varied from 0% to 78% for extremely low birth weight infants in gestational age ranges are less than 23 6/7 weeks and treatment with postnatal indomethacin within 12 hours of birth. Because only 11% of the cohort studied by Shah et al received postnatal indomethacin, the exposed infants are a highly selected subpopulation, as reported in the Qureshi et al report.…”

“…A recent example is a neurodevelopment study of all newborns in Finland (population-based) showing that women exposed to antenatal steroids for a perceived risk for preterm delivery that delivered at term had multiple indications of adverse developmental effects when assessed at Preventative Strategies in Congenital B12 Deficiency C ongenital B12 deficiency is associated with neurologic delay, impaired neurodevelopment, developmental delay and hypotonia, and lifelong increased risk of chronic disease. 1,2 Although many cases of congenital B12 deficiency are diagnosed clinically, B12 deficiency has been incidentally diagnosed by newborn screening in many countries using markers designed to detect methylmalonic aciduria. 3,4 However, the sensitivity of this approach is unknown.…”