Paracetamol Use In Pregnancy Research Articles

Paracetamol use in pregnancy does not increase risk of ADHD and autism

Paracetamol use in pregnancy does not increase risk of ADHD and autism

Paracetamol use in pregnancy: Not as safe as we may think?

Paracetamol is used by more than 50% of women worldwide during pregnancy; headache representing the most frequent indication. Several studies report that long-term exposure to paracetamol in utero is associated with adverse neurodevelopmental outcomes in children, indicating a dose-response effect. However, less or no risk is found to be associated with short-term exposure. Paracetamol most likely crosses the placenta through passive diffusion, and there are several possible mechanisms for how paracetamol might affect fetal brain development. Although the literature suggests an association between prenatal paracetamol exposure and neurodevelopmental outcomes, the role of confounders cannot be ruled out. Consequently, as a precaution, we believe that pregnant women should be recommended ideally to only use paracetamol to treat conditions that might harm the fetus, such as severe pain or a high fever. This Comment aims to put focus on the potential fetal risks of paracetamol exposure in utero.

Effects of Prenatal Paracetamol Exposure on the Development of Asthma and Wheezing in Childhood: A Systematic Review and Meta-Analysis.

The aim of the report was to evaluate whether in utero exposure to paracetamol is associated with risk towards developing respiratory disorders such as asthma and wheeze after birth. MEDLINE (PubMed), EMBASE and Cochrane Library databases were searched for articles published in English to December 2021. The study involved 330,550 women. We then calculated the summary risk estimates and 95% CIs and plotted forest plots using random effect models (DerSimonian-Laird method) and fixed effect models. We also performed a systematic review of the chosen articles and a meta-analysis of studies based on the guidelines outlined in the PRISMA statement. Accordingly, maternal exposure to paracetamol during pregnancy was associated with a significant increased risk of asthma: crude OR = 1.34, 95% CI: 1.22 to 1.48, p < 0.001; and significant increased risk of wheeze: crude OR = 1.31, 95% CI: 1.12 to 1.54, p < 0.002. Results of our study confirmed that maternal paracetamol use in pregnancy is associated with an enhanced risk of asthma and wheezing in their children. We believe paracetamol should be used with caution by pregnant women, and at the lowest effective dose, and for the shortest duration. Long-term use or the use of high doses should be limited to the indications recommended by a physician and with the mother-to-be under constant supervision.

Autism spectrum disorder related to unwarranted paracetamol use in pregnancy.

Dear Editor, There has been a rapid increase in self-medication with over-the-counter (OTC) drugs, mostly paracetamol, by pregnant women lately. [1,2] Its rampant use is due to easy availability and cost-effectiveness. Pregnant women mostly self-medicate for nausea, vomiting, backache and fever. [A study from Pakistan reported OTC drug use by 37.9% of pregnant women, whereas 77.4% of them were unaware of its indications, dosages and potential hazards. Their use of OTC drugs was based on the experience or recommendations of relatives and pharmacists. [1] This unchecked use of paracetamol can be dangerous in pregnancy because its metabolites cross the placenta and blood-brain barrier of the fetus readily and pose significant risk to the normal neurodevelopment of the fetus, by interfering with the immunologic development of the brain. [2] ---Continue

Effects of paracetamol (acetaminophen) on gene expression and permeability properties of the rat placenta and fetal brain.

Background: Paracetamol (acetaminophen) is widely used in pregnancy and generally regarded as "safe" by regulatory authorities. Methods: Clinically relevant doses of paracetamol were administered intraperitoneally to pregnant rats twice daily from embryonic day E15 to 19 (chronic) or as a single dose at E19 (acute). Control samples were from un-treated age-matched animals. At E19, rats were anaesthetised, administered a final paracetamol dose, uteruses were opened and fetuses exposed for sample collection. For RNA sequencing, placentas and fetal brains were removed and flash frozen. Fetal and maternal plasma and cerebrospinal fluid were assayed for α-fetoprotein and interleukin 1β (IL1β). Brains were fixed and examined (immunohistochemistry) for plasma protein distribution. Placental permeability to a small molecule ( 14C-sucrose) was tested by injection into either mother or individual fetuses; fetal and maternal blood was sampled at regular intervals to 90 minutes. Results: RNA sequencing revealed a large number of genes up- or down-regulated in placentas from acutely or chronically treated animals compared to controls. Most notable was down-regulation of three acute phase plasma proteins (α-fetoprotein, transferrin, transthyretin) in acute and especially chronic experiments and marked up-regulation of immune-related genes, particularly cytokines, again especially in chronically treated dams. IL1β increased in plasma of most fetuses from treated dams but to variable levels and no IL1β was detectable in plasma of control fetuses or any of the dams. Increased placental permeability appeared to be only from fetus to mother for both 14C-sucrose and α-fetoprotein, but not in the reverse direction. In the fetal brain, gene regulatory changes were less prominent than in the placenta of treated fetuses and did not involve inflammatory-related genes; there was no evidence of increased blood-brain barrier permeability. Conclusion: Results suggest that paracetamol may induce an immune-inflammatory-like response in placenta and more caution should be exercised in use of paracetamol in pregnancy.

Effects of paracetamol (acetaminophen) on gene expression and permeability properties of the rat placenta and fetal brain

Background: Paracetamol (acetaminophen) is widely used in pregnancy and generally regarded as “safe” by regulatory authorities. Methods: Clinically relevant doses of paracetamol were administered intraperitoneally to pregnant rats twice daily from embryonic day E15 to 19 (chronic) or as a single dose at E19 (acute). Control samples were from un-treated age-matched animals. At E19, rats were anaesthetised, administered a final paracetamol dose, uteruses were opened and fetuses exposed for sample collection. For RNA sequencing, placentas and fetal brains were removed and flash frozen. Fetal and maternal plasma and cerebrospinal fluid were assayed for α-fetoprotein and interleukin 1β (IL1β). Brains were fixed and examined (immunohistochemistry) for plasma protein distribution. Placental permeability to a small molecule ( 14C-sucrose) was tested by injection into either mother or individual fetuses; fetal and maternal blood was sampled at regular intervals to 90 minutes. Results: RNA sequencing revealed a large number of genes up- or down-regulated in placentas from acutely or chronically treated animals compared to controls. Most notable was down-regulation of three acute phase plasma proteins (α-fetoprotein, transferrin, transthyretin) in acute and especially chronic experiments and marked up-regulation of immune-related genes, particularly cytokines, again especially in chronically treated dams. IL1β increased in plasma of most fetuses from treated dams but to variable levels and no IL1β was detectable in plasma of control fetuses or any of the dams. Increased placental permeability appeared to be only from fetus to mother for both 14C-sucrose and α-fetoprotein, but not in the reverse direction. In the fetal brain, gene regulatory changes were less prominent than in the placenta of treated fetuses and did not involve inflammatory-related genes; there was no evidence of increased blood-brain barrier permeability. Conclusion: Results suggest that paracetamol may induce an immune-inflammatory-like response in placenta and more caution should be exercised in use of paracetamol in pregnancy.

Effects of paracetamol (acetaminophen) on gene expression and permeability properties of the rat placenta and fetal brain.

Background: Paracetamol (acetaminophen) is widely used in pregnancy and generally regarded as "safe" by regulatory authorities. Methods: Clinically relevant doses of paracetamol were administered intraperitoneally to pregnant rats twice daily from embryonic day E15 to 19 (chronic) or as a single dose at E19 (acute). Control samples were from un-treated age-matched animals. At E19, rats were anaesthetised, administered a final paracetamol dose, uteruses were opened and fetuses exposed for sample collection. For RNA sequencing, placentas and fetal brains were removed and flash frozen. Fetal and maternal plasma and cerebrospinal fluid were assayed for ⍺-fetoprotein and interleukin 1β (IL1β). Brains were fixed and examined (immunohistochemistry) for plasma protein distribution. Placental permeability to a small molecule ( 14C-sucrose) was tested by injection into either mother or individual fetuses; fetal and maternal blood was sampled at regular intervals to 90 minutes. Results: RNA sequencing revealed a large number of genes up- or down-regulated in placentas from acutely or chronically treated animals compared to controls. Most notable was down-regulation of three acute phase plasma proteins (⍺-fetoprotein, transferrin, transthyretin) in acute and especially chronic experiments and marked up-regulation of immune-related genes, particularly cytokines, again especially in chronically treated dams. IL1β increased in plasma of most fetuses from treated dams but to variable levels and no IL1β was detectable in plasma of control fetuses or any of the dams. Increased placental permeability appeared to be only from fetus to mother for both 14C-sucrose and ⍺-fetoprotein, but not in the reverse direction. In the fetal brain, gene regulatory changes were less prominent than in the placenta of treated fetuses and did not involve inflammatory-related genes; there was no evidence of increased blood-brain barrier permeability. Conclusion: Results suggest that paracetamol may induce an immune-inflammatory-like response in placenta and more caution should be exercised in use of paracetamol in pregnancy.

Role of Paracetamol in the Pathogenesis of Autism Spectrum Disorder: A Growing Perspective

Autism spectrum disorder (ASD) affecting one in every 59 newborns with significant surge in the prevalence rates over last few decades has complex underlying pathophysiological mechanism which is not fully understood. We hypothesize that such association might be associated with paracetamol-induced alterations in cytokine levels, oxidative stress and dysregulation of neurotransmission, especially dopaminergic pathways. Additionally, disruption of prostaglandin synthesis following paracetamol administration has considerable impact over neurodevelopment. We performed literature review by searching our topic of interest on three databases including PubMed, Embase and the Cochrane library by utilizing keywords. Recent large scale nationwide birth cohort studies implicate link between paracetamol use during pregnancy, most commonly utilized anti-pyretic and analgesic medication at that period, and risk of autism in infants. Alterations at cytokine and prostaglandin levels, elevated oxidative stress and impairment of neurotransmission may have role in ASD pathogenesis, though, it has not been demonstrated in human studies. There is clear need for future comprehensive molecular and clinical studies to investigate the association between paracetamol use in pregnancy and ASD risk. This study is significant by investigating the role of paracetamol use in upward projection in ASD prevalence and providing a hypothetical underlying mechanism for the association between paracetamol use and ASD risk.

Maternal Infections, Antibiotics, and Paracetamol in Pregnancy and Offspring Celiac Disease: A Cohort Study.

Infections in pregnancy are common, may affect fetal development, and have been linked to offspring autoimmunity. We aimed to determine whether maternal infections, the use of antibiotics, and use of paracetamol in pregnancy are associated with the risk of offspring celiac disease (CD). The nationwide Norwegian Mother and Child Cohort Study includes 84,274 children born in the period from 2000 to 2009 with prospectively collected questionnaire data on maternal infections and medication use in pregnancy. CD was identified through questionnaires and the Norwegian Patient Register. Logistic regression yielded odds ratios adjusted for age and sex (aORs). During a median follow-up of 8.5 years, 617 children (0.7%) were diagnosed with CD. The aOR for offspring CD per increase in number of maternal infections was 1.07 (95% confidence interval [CI] = 1.01-1.13), but not significantly increased for categories 1 infection (1.01 [95% CI = 0.82-1.25]) and ≥2 infections (1.22 [95% CI = 1.00-1.49]) versus no infection. We found the same pattern for respiratory tract infections, but not for gastrointestinal infections. The aORs were broadly consistent across pregnancy periods of exposure. The use of antibiotics and paracetamol was, compared with no use, not associated with offspring CD (aOR = 1.16 [95% CI = 0.94-1.43] and aOR = 1.13 [95% CI = 0.96-1.33], respectively; P values for trend >0.2). In this large pregnancy cohort we found no clear association between maternal infections in pregnancy and offspring CD, but considering the marginal significance in some of our results maternal infections cannot be ruled out as a risk factor. Reassuringly for both parents-to-be and clinicians, the use of antibiotics and paracetamol in pregnancy was not a significant risk factor.

Paracetamol use in pregnancy linked to childhood behaviour problems

Paracetamol use in pregnancy linked to childhood behaviour problems

Prolonged paracetamol use in pregnancy could harm male offspring

Prolonged paracetamol use in pregnancy could harm male offspring

Effect of prenatal exposure to fine particulate matter and intake of Paracetamol (Acetaminophen) in pregnancy on eczema occurrence in early childhood

The goal of the study was to test the hypothesis that prenatal Paracetamol exposure increases the risk of developing eczema in early childhood and that this association may be stronger in children who are exposed in fetal period to higher concentrations of fine particulate matter (PM2.5). The study sample consisted of 322 women recruited from January 2001 to February 2004 in the Krakow inner city area who gave birth to term babies and completed 5-year follow-up. Paracetamol use in pregnancy was collected by interviews and prenatal personal exposure to PM2.5 over 48h was measured in recruited women in the second trimester of pregnancy. After delivery, every three months in the first 24months of the newborn's life and every 6months later, a detailed standardized face-to-face interview on the infant's health was administered to each mother by trained interviewers. During the interviews at each of the study periods after birth, a history of eczema was recorded.The incident rate ratio (IRR) for frequency of eczema events over the follow-up was estimated from the Poisson regression model and the overall effect of main exposure variables on eczema was assessed by odds ratios (ORs) by the logistic model. The estimated relative risk of eczema occurring whenever in the follow-up was related significantly neither with prenatal Paracetamol nor higher PM2.5 exposure, however, their joint effect was significant (OR interaction term=6.04; 95%CI: 1.04–35.16). Of potential confounders considered in the analysis only damp/moldy home significantly increased the risk of eczema (OR=1.53; 95%CI: 1.14–2.05). In contrast, there was an inverse significant association between the presence of older siblings and eczema (OR=0.55; 95%CI: 0.35–0.84). The joint effect of the main exposure variables significantly increased frequency of eczema events (IRR=1.78, 95%CI: 1.22–2.61).In conclusion, the findings of the study suggest that Paracetamol use by mothers in pregnancy is not an independent risk factor for eczema in children, however, even very small doses of Paracetamol taken in pregnancy may contribute to the occurrence of allergic symptoms in early childhood if there is prenatal co-exposure to higher airborne fine particulate matter.

Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta‐analysis

There is evidence to suggest that the risk of asthma might be increased with exposure to paracetamol in the intrauterine environment, infancy, later childhood and adult life. To review the evidence from studies investigating the association between paracetamol use in pregnancy and childhood asthma. A systematic review and meta-analysis was undertaken of studies reporting the association between paracetamol use in pregnancy and subsequent asthma in childhood. The primary outcome variable was wheeze in the last 12 months. For tabulated raw data, not adjusted for confounders, random effects odds ratios (OR) were pooled by the inverse variance weighted method. There were six studies identified that were included in the meta-analysis. The age of children studied ranged from 30 to 84 months. The pooled random effects OR for the risk of current wheeze in the children of women who were exposed to any paracetamol during any stage of pregnancy was 1.21 (95% confidence interval 1.02-1.44). Features of the studies variably included an association with paracetamol use during all trimesters of pregnancy and an association with persistent asthma, severe asthma, and with atopy. The use of paracetamol during pregnancy is associated with an increased risk of childhood asthma. More research is urgently required to determine the impact of paracetamol during pregnancy on the risk of wheezing in offspring so that appropriate public health recommendations can be made.

Prenatal paracetamol exposure and asthma: further evidence against confounding

Observational studies have reported an association between maternal use of paracetamol in pregnancy and childhood asthma, which was not explained by measured confounding factors. However, it is possible that this relation might be confounded by unmeasured behavioural factors linked to paracetamol usage; if that were the case, effects of similar magnitude of partner's paracetamol use and/or postnatal maternal use would be expected. In the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort, we compared the univariate effects of maternal use of paracetamol in pregnancy on risk of doctor-diagnosed asthma, wheeze and elevated immunoglobulin E (IgE) in the offspring at 7 years of age, with the univariate effects of partner's use and postnatal maternal use on these phenotypes. Maternal use of paracetamol in pregnancy was strongly associated with all outcomes. Partner's use was very weakly associated with asthma but not associated with wheezing or IgE. Postnatal maternal use was associated with asthma and wheezing, though less strongly than was prenatal use, and was not associated with IgE. On mutual adjustment, the effects of maternal use in pregnancy on all outcomes were not substantially attenuated, whereas the effects of partner's use on asthma, and of postnatal maternal use on asthma and wheezing, were reduced. These findings suggest that the relation between maternal use of paracetamol in pregnancy and childhood asthma is unlikely to be confounded by unmeasured behavioural factors linked to paracetamol use.

Paracetamol use in pregnancy and wheezing in early childhood

Background: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing...