Preconception use of pain-relievers and time-to-pregnancy: a prospective cohort study

McInerney, Kathryn A.; Hatch, Elizabeth E.; Wesselink, Amelia K.; Rothman, Kenneth J.; Mikkelsen, Ellen M.; Wise, Lauren A.

doi:10.1093/humrep/dew272

Cited by 12 publications

(11 citation statements)

References 36 publications

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“…Currently, pregnant women are advised against nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen because studies have associated first-trimester use with increased risk for miscarriage (Nakhai-Pour et al, 2011) and cardiac malformations (Ericson and K€ all en, 2001) and third-trimester use with premature closure of the ductus arteriosus (Koren et al, 2006), renal impairment (Bennett et al, 1996), and other adverse health effects in childhood (Nezvalova-Henriksen et al, 2013. Further, use during the peri-conceptual period is associated with reduced female fecundity (McInerney et al, 2017). Similarly, most pregnant women are advised against using high doses of aspirin, or using aspirin for extended periods (James et al, 2008;Rumack et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Association Between Meconium Acetaminophen and Childhood Neurocognitive Development in GESTE, a Canadian Cohort Study

Laue

Cassoulet

Abdelouahab

et al. 2018

Toxicological Sciences

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Acetaminophen is the only over-the-counter pain reliever that is not contraindicated during pregnancy, but recent studies have questioned whether acetaminophen is safe for the fetus, particularly the developing brain. This prospective birth cohort study probed the previously observed association between in utero exposure to acetaminophen and neurodevelopment by using concentrations of acetaminophen measured in meconium, which more objectively captures exposure of the fetus than maternal report. Exposure, measured by liquid chromatography coupled with tandem mass spectrometry, was categorized into non-detection, low detection, and high detection levels. At age six to eight years, children completed a set of subtests from the Wechsler Intelligence Scale for Children, 4th edition. Additionally this study examined potential effect modification by child sex on the association between acetaminophen exposure and neurodevelopment. In fully adjusted models, in utero exposure to acetaminophen was not statistically significantly associated with decreased scores on any of the examined subtests in all children combined (n = 118). The effect of in utero acetaminophen exposure on the Coding subtest was marginally significantly different among boys and girls, with girls performing significantly better on the task with higher levels of acetaminophen compared to girls with undetectable levels of exposure [βgirls, low = 2.83 (0.97, 4.70), βgirls, high = 1.95 (-0.03, 3.93), βboys, low = 0.02 (-1.78, 1.81), βboys, high = -0.39 (-2.09, 1.31), pinteraction = 0.06]. Effect modification by child sex was not observed on other subtests. These results do not support prior reports of adverse neurodevelopmental effects of in utero exposure to acetaminophen.

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Section: Discussionmentioning

confidence: 99%

Association Between Meconium Acetaminophen and Childhood Neurocognitive Development in GESTE, a Canadian Cohort Study

Laue

Cassoulet

Abdelouahab

et al. 2018

Toxicological Sciences

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“…Research on multiple species has shown adverse effects of aspirin and indomethacin on ovulation through prostaglandin disruption (Sirois et al, 2004). Pre-conception consumption of NSAID's has also been associated with effects on implantation and reduced female fecundability (Mcinerney et al, 2017); however, peri-implantation use of aspirin was associated with increased fecundability (Jukic et al, 2020). Other findings in female adults include analgesic-induced disruption of menstruation and ovulation (Meyboom et al, 1995;Salman et al, 2015).…”

Section: Reproductive Defectsmentioning

confidence: 99%

Over-the-counter analgesics during pregnancy: a comprehensive review of global prevalence and offspring safety

Zafeiri

Mitchell

Hay

et al. 2020

Human Reproduction Update

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BACKGROUND Analgesia during pregnancy is often necessary. Due to their widespread availability, many mothers opt to use over-the-counter (OTC) analgesics. Those analgesic compounds and their metabolites can readily cross the placenta and reach the developing foetus. Evidence for safety or associations with adverse health outcomes is conflicting, limiting definitive decision-making for healthcare professionals. OBJECTIVE AND RATIONALE This review provides a detailed and objective overview of research in this field. We consider the global prevalence of OTC analgesia during pregnancy, explain the current mechanistic understanding of how analgesic compounds cross the placenta and reach the foetus, and review current research on exposure associations with offspring health outcomes. SEARCH METHODS A comprehensive English language literature search was conducted using PubMed and Scopus databases. Different combinations of key search terms were used including ‘over-the-counter/non-prescription analgesics’, ‘pregnancy’, ‘self-medication’, ‘paracetamol’, ‘acetaminophen’, ‘diclofenac’, ‘aspirin’, ‘ibuprofen’, ‘in utero exposure’, ‘placenta drug transport’, ‘placental transporters’, ‘placenta drug metabolism’ and ‘offspring outcomes’. OUTCOMES This article examines the evidence of foetal exposure to OTC analgesia, starting from different routes of exposure to evidence, or the lack thereof, linking maternal consumption to offspring ill health. There is a very high prevalence of maternal consumption of OTC analgesics globally, which is increasing sharply. The choice of analgesia selected by pregnant women differs across populations. Location was also observed to have an effect on prevalence of use, with more developed countries reporting the highest consumption rates. Some of the literature focuses on the association of in utero exposure at different pregnancy trimesters and the development of neurodevelopmental, cardiovascular, respiratory and reproductive defects. This is in contrast to other studies which report no associations. WIDER IMPLICATIONS The high prevalence and the challenges of reporting exact consumption rates make OTC analgesia during pregnancy a pressing reproductive health issue globally. Even though some healthcare policy-making authorities have declared the consumption of some OTC analgesics for most stages of pregnancy to be safe, such decisions are often based on partial review of literature. Our comprehensive review of current evidence highlights that important knowledge gaps still exist. Those areas require further research in order to provide pregnant mothers with clear guidance with regard to OTC analgesic use during pregnancy.

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“…In another study, it was reported that glutathione concentration decreased in the fetal mouse liver without any malformation due to the paracetamol application to the mice between the 6th and 13th days of their pregnancy [21]. Oxidative stress stimulates the formation of mitochondrial peroxynitritis, which triggers mitochondrial DNA damage, and hepatic macrophages advance liver damage from paracetamol [2].…”

Section: Discussionmentioning

confidence: 97%

“…P aracetamol has been widely used worldwide since its release in the mid-1950s due to its painrelieving and antipyretic effects [1]. Nonsteroidal anti-inflammatory drugs are frequently used among pregnant women, preferred for its availability to be purchased without a prescription [2]. Paracetamol is a pain reliever that is widely used due to its reliability, cheapness and effectiveness [3].…”

Section: Introductionmentioning

confidence: 99%

Effects of Paracetamol on Vascular Endothelial Growth Factor, Sclerostin and FETUIN-A in the Liver of Rat Fetuses

et al. 2020

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Amaç: Parasetamol gebe, çocuk ve yaşlılar gibi önemli gruplar tarafından yaygın olarak kullanılmaktadır. Özellikle gebelikte fazla dozda alınan parasetamol karaciğer yetmezliklerine neden olmaktadır. Çalışmamızın amacı gebelik döneminde yaygın olarak olarak kullanılan parasetamolün fetüs karaciğeri üzerine etkilerini biyokimyasal olarak araştırmaktır. Yöntemler: Çalışmamızda 10 adet (n=2) gebe sıçanlardan Wistar Albino cinsi rastgele seçilen kontrol grubu, 50 mg/kg parasetamol grubu, 125 mg/kg parasetamol grubu, 250 mg/kg parasetamol grubu ve 500 mg/kg parasetamol grubu olmak üzere beş gruba ayrıldı. Gavaj yoluyla parasetamol, belirlenen dozlarda gebe sıçanlara verildi. Gebeliğin 20. gününde sezeryan ile fetüsler alındı (her gruptan 10 adet fetus alındı). Sonrasında fetus karaciğerleri biyokimysasal analiz için alındı. Biyokimyasal olarak vascular endothelial growth factor A (VEGF-A), FETU-A (α2-heremans-schmid glikoprotein) ve Sclerostin (SOST) değerleri incelendi. Bulgular: Bu çalışmada parasetamol dozu arttıkça karaciğer hepatosit hücrelerinde değişiklikler görülmektedir. VEGF-A ve FETU-A'da düzenli artış görülmektedir. SOST ise 250 mg/kg dozunda yükselirken, 500 mg/kg parasetamol grubunda azalmıştır. (p<0.05) Sonuç: Sonuç olarak gebelikte yüksek dozda parasetamol kullanımının fetüskaraciğerinde ve biyokimyasal değerde değişiklik meydana getirdiği görülmektedir. Bu çalışmada gebelikte masum analjezik olarak reçetesiz satılan ve çok kullanılan parasetamol'un yüksek dozda kullanımı konusunda dikkat edilmesi gerektiğini ve bu çalışmanın yapılacak diğer çalışmalara referans olacağını düşünmekteyiz.

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Preconception use of pain-relievers and time-to-pregnancy: a prospective cohort study

Abstract: Not applicable.

Cited by 12 publications

References 36 publications

Association Between Meconium Acetaminophen and Childhood Neurocognitive Development in GESTE, a Canadian Cohort Study

Association Between Meconium Acetaminophen and Childhood Neurocognitive Development in GESTE, a Canadian Cohort Study

Over-the-counter analgesics during pregnancy: a comprehensive review of global prevalence and offspring safety

Effects of Paracetamol on Vascular Endothelial Growth Factor, Sclerostin and FETUIN-A in the Liver of Rat Fetuses

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