Indomethacin Prophylaxis to Prevent Intraventricular Hemorrhage: Association between Incidence and Timing of Drug Administration

Abstract

Objective To test the hypothesis that administration of indomethacin prophylaxis before 6 hours of life results in a lower incidence of intraventricular hemorrhage (IVH) compared with administration after 6 hours of life, and that the effects of early prophylaxis depend on gestational age (GA) and sex in very low birth weight infants (birth weight <1250 g). Study design Very low birth weight infants admitted to our neonatal intensive care unit between 2003 and 2010 who received indomethacin prophylaxis were analyzed retrospectively. Exclusion criteria included unknown time of indomethacin prophylaxis, death at <12 hours of life, congenital anomalies, and unavailable head ultrasound report. Infants were dichotomized based on the timing of indomethacin prophylaxis (<6 hours or >6 hours of life) to compare incidence of IVH all grades and severe (grade 3–4) IVH. Secondary analyses examined the effects of the time of indomethacin prophylaxis initiation by GA and sex on the incidence of IVH. Results A total of 868 infants (431 males and 437 females) met the criteria for analysis. Indomethacin prophylaxis was given at <6 hours of life in 730 infants and at >6 hours of life to 168 infants. The 2 groups differed with respect to antenatal steroid exposure, GA, outborn prevalence, and pneumothoraces. After multivariate analysis, there were no between-group differences in all-grade or severe IVH. However, females, but not males, treated at <6 hours of life had a lower incidence of severe IVH (P < .05), particularly at lower GAs. Conclusion Prophylactic indomethacin administered before 6 hours of life is not associated with lower incidence of IVH.

Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants

“…(11) Data available from the NICHD Neonatal Research Network Generic Database provided the opportunity to examine the time of administration of indomethacin in a larger cohort derived from multiple centers. We confirmed that indomethacin prophylaxis before 6 hours of age does not decrease the incidence of IVH or death compared to later administration up to 24 h of age.…”

Hospital volume and mortality due to preterm patent ductus arteriosus

“…Finally, the present study may have overestimated the number of PDA patients because indomethacin is also used to prevent IVH in premature infants. 21 In conclusion, there were no significant differences in mortality due to preterm PDA according to hospital volume. Surgical and medical treatment methods had a similar mortality, and there was no evidence to support the necessity for centralization of institutions treating PDA, at least in Japan.…”

“…Second, the diagnoses that are recoded in administrative claims databases are generally less well validated than those in prospective studies. Finally, the present study may have overestimated the number of PDA patients because indomethacin is also used to prevent IVH in premature infants …”

Neuroprotective effect of indomethacin in normal perfusion pressure breakthrough phenomenon

“…Thus, IVH in these infants has been attributed to changes in CBF in the periventricular germinal matrix, due to the particular structure of the matrix and micro vessels immaturity 10 . Indomethacin administration during the first day of life has been proven as an effective measure to prevent IVH, particularly severe grades 12 , 42 – 44 . Thus, indomethacin may reduce the hyperemic response favouring cerebral autoregulation 28 , 32 , 33 , promoting microvascular maturation in the germinal matrix 32 , 36 , 41 , and inhibiting changes in BBB permeability 28 .…”