University of Oulu

Laitala, A, Saarela, T, Vääräsmäki, M, Hallman, M, Aikio, O. Paracetamol preceding very preterm birth: Is it safe?. Acta Obstet Gynecol Scand. 2022; 101: 901- 909. doi: 10.1111/aogs.14405

Paracetamol preceding very preterm birth : is it safe?

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Author: Laitala, Aliisa1; Saarela, Timo1; Vääräsmäki, Marja2;
Organizations: 1PEDEGO Research Unit and MRC Oulu, University of Oulu and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
2PEDEGO Reseach Unit and MRC Oulu and Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2022-08-05


Introduction: The use of paracetamol for pain relief in pregnancy is common. However, the influence of paracetamol on the perinatal adaptation of high-risk infants has not been studied. These data are important for safety, since another inhibitor of prostaglandin synthesis is harmful to infants born very preterm and increases serious morbidity. We studied whether the use of paracetamol had an adverse influence on neonatal adaptation and the outcomes of infants during the first hospitalization.

Material and Methods: We studied the patient records of high-risk mothers and their infants born before 32 weeks of gestation for multiple variables over a period of 84 months in Oulu University Hospital, a regional tertiary care hospital caring for high-risk deliveries and providing neonatal intensive care. In a matched cohort setting, the exposition was defined as paracetamol use <24 h before childbirth. The controls had consumed no paracetamol up to 1 week before delivery. Infants with major anomalies were excluded. The primary outcome was defined as the need for early interventional treatments for the preterm infants. Outcomes during the first hospitalization were also studied.

Results: Altogether, 170 fetuses from 149 mothers were exposed to paracetamol during the study period. The control population, delivering during the same period, consisted of 118 non-exposed fetuses from 104 mothers. Among them, the mothers were pairwise matched according to their medications, amniotic fluid leakage time, clinical infections, and delivery mode. After matching, 72 mothers/group remained, resulting in 88 paracetamol-exposed infants and 85 controls. No perinatal adverse reactions were detected. There were no differences in either circulatory support during the first postnatal day or in the risk for major diseases during the first hospitalization. Paracetamol-exposed infants needed fewer acute delivery room therapies (51.1% vs 65.9%, mean difference −14.89; 95% confidence interval −0.29 to −0.003). Maternal total paracetamol dose in the 1 week before delivery correlated positively with Apgar scores.

Conclusions: Antenatal paracetamol given within 24 h before birth had no adverse effects on extremely or very preterm infants. The long-term safety of paracetamol and the potential acute benefits for preterm infants during perinatal transition remain to be proven in larger, prospective settings.

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Series: Acta obstetricia et gynecologica Scandinavica
ISSN: 0001-6349
ISSN-E: 1600-0412
ISSN-L: 0001-6349
Volume: 101
Issue: 8
Pages: 901 - 909
DOI: 10.1111/aogs.14405
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: This study was supported by grants from the Alma and K.A. Snellman Foundation, Oulu, Finland (AL, OA), the Finnish Medical Foundation (OA), the Foundation for Pediatric Research (OA), and the Sigrid Jusélius Foundation (MH).
Copyright information: © 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.