The association of platelets with failed patent ductus arteriosus closure after a primary course of indomethacin or ibuprofen: a systematic review and meta-analysis

Abstract

Objective: To conduct a meta-analysis of the association of platelet counts and pharmacotherapeutic failure in preterms with a patent ductus arteriosus (PDA).

Methods: MEDLINE, Embase, Science Citation Index, abstracts and conference proceedings were searched, and principal authors contacted. Included studies reported indomethacin or ibuprofen use for PDA closure, compared a group which failed treatment versus a group which did not and reported the association between platelet counts and indomethacin or ibuprofen failure. Two reviewers independently screened results and assessed methodological quality using the Newcastle-Ottawa Scale. Results are expressed as mean difference in platelet counts and summary odds ratios (OR) using a random effects model.

Results: 1105 relevant studies were identified; eight involving 1087 preterms were included. Platelet counts were significantly lower in infants who failed pharmacotherapy (Meandifference:–30.88 × 10⁹/L; 95% CI:–45.69 × 10⁹,–16.07 × 10⁹/L; I2 = 24%; p_{heterogeneity}=0.24). Similar results were obtained based on either pharmacotherapeutic agent. Treatment failure was also significantly associated with pre-treatment thrombocytopenia (summary OR:1.75; 95% CI:1.23–2.49, I2 = 36%, p_{heterogeneity}=0.20).

Conclusions: Platelet counts are significantly lower in preterms who fail primary treatment for PDA. Pre-treatment thrombocytopenia is associated with higher odds of failure. Further cohort studies reporting platelet counts in prostaglandin inhibitor failure are needed for meta-analyses to firmly establish or refute a stronger association.

• Closure
• failed primary therapy
• ibuprofen
• indomethacin
• patent ductus arteriosus
• meta-analysis

Acknowledgements

We thank Dr Evrim Alyamac Dizdar, Department of Neonatology, Zekai Tahir Burak Maternity and Teaching Hospital, Ankara, Turkey and Dr Federico Schena, Neonatology and Neonatal Intensive Care Unit, Fondazione IRCCS Ca’ GrandaOspedale Maggiore Policlinico, Milan, Italy, for providing additional data from their original studies for our analyses.

Declaration of interest

The authors report no declarations of interest.

Supplementary materials available online