Many women avoid drugs of any kind during pregnancy, however some seek out treatments from over-the-counter painkillers to combat morning sickness.
More importantly — they say that there is no clear evidence that it has any harmful effects on an unborn baby. However, a study published in JAMA Pediatrics contradicts this and said that children whose mothers took paracetamol when pregnant were at an increased risk of developing issues such as hyperactivity and emotional problems by the time they turn seven.
The NHS recommend that pregnant women should not take paracetamol pills containing caffeine often used by people who feel sick but need to stay awake.
High levels of caffeine can result in babies having a low birth weight, which can increase the risk of health problems in later life. As always, if you are concerned about taking medication or anything else while you are pregnant, speak to your doctor.
However, when third trimester intake doses and duration was additionally taken into account, our data indicated some effect of higher daily intake doses as well as a more continuous regular intake Fig. However, small numbers per group precluded us from detecting significant dose-dependent effects.
Hence, larger group sizes would be needed, which are difficult to obtain in observational studies due to ethical considerations. Nevertheless, these findings imply that even within the range of the maximum daily dosage the application of Paracetamol may alter immune relevant cell frequencies. The finding of a special relevance of third trimester Paracetamol intake bears tremendous clinical implications, as Paracetamol is considered one of the few analgesics safe to use in the last trimester of pregnancy.
Other findings supported that the intake in the third trimester seems to be a crucial hallmark in NSAID therapy Tanaka et al. Concordant to our findings a UK based study found that 3rd trimester intake of Paracetamol bears the highest risk of asthma development Shaheen et al. In a study by Shaheen et al. Importantly, considering also our observation of increased intake dosages taken during the 3rd trimester, effects on the HSCs might become even more prominent.
The underlying mechanism for a particular relevance in the third trimester remains elusive. It is tempting to speculate on a time dependent relation, or an easier Paracetamol passage through the placenta due to change in the vascularization. Structural alterations of capillaries to sinusoids, to meet the needs of the fetus, might additional favor the transmission of Paracetamol Milovanov et al.
Paracetamol has been shown to be flow-limited in its transmission through the placenta Nitsche et al. Whether hydrodynamics or epithelial factors in an aging placenta support an altered Paracetamol transmission has yet to be elucidated.
Nevertheless, Paracetamol is known to pass the placenta freely and can easily reach sites of HSC in the fetus, e. Application of Paracetamol in pregnant mice has been shown to decrease HSC frequencies in the fetal liver Karimi et al. Thus, it has been proposed that fetal HSC sites may be particularly susceptible to Paracetamol-induced hepatotoxicity, subsequently leading to a decline of HSCs. Such altered HSC pool may have consequences for the differentiation of HSCs in the different cell lineages, hereby affecting immunity of the offspring.
The present results add valuable detailed data on Paracetamol intake during pregnancy and indicate a particular relevance of third trimester Paracetamol intake, which was prospectively associated with a reduced frequency of HSCs. Future studies are needed to disentangle potential trimester-specific effects and elucidate the impact of maternal medication onto the offspring's health with a special focus on immune development. We finally would like to stress that we acknowledge the importance of Paracetamol medication during pregnancy to prevent more severe consequences caused by fever and infections.
There might however be circumstances, where Paracetamol is rather taken out of habit and because it is a cheap and generally available medication. From our perspective it is important to tackle these cases through education on possible adverse side-effects of Paracetamol during pregnancy.
The funding agency was not involved in any further scientific decision. LB and JG analyzed and interpreted the data, searched the literature, and wrote the manuscript; LB drafted the graphical abstract; JG conducted the figures; CW analyzed the data and conducted the figures; MP recruited the participants and collected the data; CG collected the FACS data and prepared the figure; HB supervised the data analysis; KH and PA conceived the study; AD and GT supervised the project; all authors critically revised the manuscript and approved the final version.
We further would like to thank Gudula Hansen and Dr. National Center for Biotechnology Information , U. Journal List EBioMedicine v. Published online Nov 9. Petra C. Author information Article notes Copyright and License information Disclaimer. Lars Bremer: ed. J ; Christian Wiessner: ed. C ; Mirja Pagenkemper: ed.
M ; Christina Gehbauer: ed. C ; Heiko Becher: ed. H ; Eva Tolosa: ed. E ; Kurt Hecher: ed. K ; Petra C. Arck: ed. P ; Anke Diemert: ed. A ; Gisa Tiegs: ed. This article has been cited by other articles in PMC. Associated Data Supplementary Materials Supplementary material. Abstract Background Paracetamol is the first choice for antipyretic or analgesic treatment throughout pregnancy. Interpretation Prenatal Paracetamol intake, especially during the third trimester, may be causally involved in decreasing HSCs in cord blood.
Graphical Abstract. Open in a separate window. Introduction While fever and pain are debilitating and endangering, especially during pregnancy, medication might evoke long-term side effects in the offspring. Aim The aim of our present study was to determine the intake pattern of Paracetamol during pregnancy in a longitudinal study. Material and Methods 3. Flow chart of the study sample. Abbreviations used: FACS, fluorescence-activated cell sorting.
Assessment of Analgesic Medication At each study visit, medication intake was assessed via a questionnaire assisted interview from the study gynecologists. Statistical Analyses Descriptive statistics were used to present analgesic intake in the cohort: Group comparisons were made using t -test or ANOVA for normally distributed continuous variables, Kruskal-Wallis test for not normally distributed continuous variables and Chi-square test for categorical variables.
Results Of the women with analgesic intake data in each trimester, women Detailed Data on Paracetamol Intake During Pregnancy Among women taking analgesics, the percentage of women using Paracetamol increases throughout pregnancy, while the percentage of women taking ibuprofen, the second most relevant analgesic drug, decreases Supplemental Fig.
Table 2 Paracetamol intake doses and duration in each trimester of pregnancy a. Discussion This study presents detailed data of Paracetamol intake during pregnancy. Outlook The present results add valuable detailed data on Paracetamol intake during pregnancy and indicate a particular relevance of third trimester Paracetamol intake, which was prospectively associated with a reduced frequency of HSCs. Conflicts of Interest The authors declare no conflict of interest.
Author Contributions LB and JG analyzed and interpreted the data, searched the literature, and wrote the manuscript; LB drafted the graphical abstract; JG conducted the figures; CW analyzed the data and conducted the figures; MP recruited the participants and collected the data; CG collected the FACS data and prepared the figure; HB supervised the data analysis; KH and PA conceived the study; AD and GT supervised the project; all authors critically revised the manuscript and approved the final version.
They found those women who used more than one painkiller simultaneously, such as paracetamol and ibuprofen, had a seven-fold increased risk of giving birth to sons with some form of undescended testes, or cryptorchidism, compared to women who took nothing.
The second trimester - 14 to 27 weeks of pregnancy - appeared to be a particularly sensitive time. Any analgesic use at this point in the pregnancy was linked to more than double the risk of cryptorchidism.
Of the individual painkillers, ibuprofen and aspirin use were linked with a quadrupled risk. Paracetamol alone also appeared to raise the risk, although this result was not statistically significant. Simultaneous use of more than one painkiller, including paracetamol, during the second trimester increased the risk fold. Taking painkillers for more than two weeks at a time also appeared to raise the risk significantly. The researchers suspect that painkillers upset the natural balance of male hormones at work in unborn baby boys and this hinders normal development.
Studies of rats back this theory. Dr Henrik Leffers, senior scientist at Rigshospitalet in Copenhagen, who led the research, said: "If exposure to endocrine disruptors is the mechanism behind the increasing reproductive problems among young men in the Western world, this research suggests that particular attention should be paid to the use of mild analgesics during pregnancy, as this could be a major reason for the problems.
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