The effect of antenatal indomethacin on extremely preterm neonatal kidney function

Abstract Introduction/Objective: Indomethacin is an effective tocolytic to prevent extremely preterm birth. Prior studies have associated antenatal indomethacin exposure with adverse preterm neonatal intestinal and neurological outcomes. Indomethacin is a nephrotoxic medication that may also affect preterm neonatal kidneys. We sought to evaluate the effect of antenatal indomethacin on extremely preterm neonatal kidney function and acute kidney injury (AKI) in the first week of age. Methods: A retrospective cohort study was conducted on neonates born < 29 weeks at a level III neonatal intensive care unit (NICU) from January 2018-April 2019. Serum creatinine (sCr) values and urine output (UOP) in the first seven days of age and the neonate’s peak serum creatinine within the first 30 days were evaluated. Neonatal AKI was defined by the modified neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition including urine output. Results: 17 of the 55 neonates meeting criteria for this study were exposed to indomethacin. The average gestational age at birth was similar between study groups. Maternal preeclampsia was more common among women who did not receive indomethacin (p = 0.021). Indomethacin exposed neonates received more gentamicin (p = 0.024). Overall, staging of the neonatal AKI did not differ significantly between the study groups, regardless of how it was quantified (sCr or UOP) or the duration of time in which the injury developed (7 days or 30 days). Separate analysis of sCr and UOP in the first seven days also failed to show any statistically significant differences between the two groups. Conclusion: In this small cohort study of extremely preterm neonates, those born to mothers treated with indomethacin did not have an increased incidence of AKI compared to neonates born to unexposed mothers. Although no statistically significant differences in UOP or sCr were found, they deserve further evaluation in adequately powered prospective clinical trials. Future prospective studies with long-term follow-up utilizing advanced biomarkers are needed to determine how antenatal indomethacin affects extremely preterm neonatal kidney function in the NICU, during childhood, and as adults.

[1]  R. Guillet,et al.  Association Between Early Caffeine Citrate Administration and Risk of Acute Kidney Injury in Preterm Neonates: Results From the AWAKEN Study , 2018, JAMA pediatrics.

[2]  Craig S. Wong,et al.  Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study , 2017, The Lancet. Child & adolescent health.

[3]  J. Swanson,et al.  Caffeine Exposure and Risk of Acute Kidney Injury in a Retrospective Cohort of Very Low Birth Weight Neonates. , 2016, The Journal of pediatrics.

[4]  G. Saade,et al.  Perinatal Outcomes after Short versus Prolonged Indomethacin for Tocolysis in Women with Preterm Labor , 2016, American Journal of Perinatology.

[5]  A. Kaunitz,et al.  Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis. , 2015, American journal of obstetrics and gynecology.

[6]  Rick W. Martin,et al.  Effect of antenatal tocolysis on neonatal outcomes , 2012, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[7]  R. Clark,et al.  Antenatal indomethacin is more likely associated with spontaneous intestinal perforation rather than NEC. , 2008, American journal of obstetrics and gynecology.

[8]  R. A. Sinkin,et al.  Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes. , 2007, American journal of obstetrics and gynecology.

[9]  V. Fanos,et al.  Postnatal renal function in preterm newborns: a role of diseases, drugs and therapeutic interventions , 2006, Pediatric Nephrology.

[10]  W. Grobman,et al.  The effect of short-term indomethacin therapy on amniotic fluid volume. , 2004, American journal of obstetrics and gynecology.

[11]  R. Harris,et al.  Cyclooxygenase-2 inhibition and renal physiology. , 2002, The American journal of cardiology.

[12]  G. Macones,et al.  The controversy surrounding indomethacin for tocolysis. , 2001, American journal of obstetrics and gynecology.

[13]  J. Hauth,et al.  Preterm delivery after indomethacin. A risk factor for neonatal complications? , 1996, The Journal of reproductive medicine.

[14]  A. Many,et al.  Effect of indomethacin on individual amniotic fluid indices in multiple gestations. , 1996, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[15]  Yukihiro Takahashi,et al.  Renal impairment in very low birthweight infants following antenatal indomethacin administration , 1994, Acta paediatrica Japonica : Overseas edition.

[16]  J. Kuller,et al.  Neonatal complications after the administration of indomethacin for preterm labor , 1993, The New England journal of medicine.

[17]  F. Ozcan,et al.  Oligohydramnios induced by maternal indomethacin therapy. , 1992, International journal of clinical pharmacology, therapy, and toxicology.

[18]  K. Moise,et al.  Long-Term Indomethacin Therapy Decreases Fetal Urine Output and Results in Oligohydramnios , 1991, American journal of perinatology.