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Author(s): Eun-Young Choi 1, Han Eol Jeong 1,2, Yunha Noh 1,2, Ahhyung Choi 1, Dong Keon Yon 3,4, Jung Yeol Han 5, Ji-Hee Sung 6, Seung-Ah Choe 7, Ju-Young Shin [...], Background Existing data on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during late pregnancy is well established, providing assurance. However, the use of NSAIDs during early pregnancy remains inconclusive owing to conflicting findings on adverse neonatal outcomes as well as the limited data on adverse maternal outcomes. Therefore, we sought to investigate whether early prenatal exposure to NSAIDs was associated with neonatal and maternal adverse outcomes. Methods and findings We conducted a nationwide, population-based cohort study using Korea's National Health Insurance Service (NHIS) database with a mother-offspring cohort constructed and validated by the NHIS to include all live births in women aged 18 to 44 years between 2010 and 2018. We defined exposure to NSAIDs as at least two records of NSAID prescriptions during early pregnancy (first 90 days of pregnancy for congenital malformations and first 19 weeks for nonmalformation outcomes) and compared against three distinct referent groups of (1) unexposed, no NSAID prescription during the 3 months before pregnancy start to end of early pregnancy; (2) acetaminophen-exposed, at least two acetaminophen prescriptions during early pregnancy (i.e., active comparator); and (3) past users, at least two NSAID prescriptions before the start of pregnancy but no relevant prescriptions during pregnancy. Outcomes of interest were adverse birth outcomes of major congenital malformations and low birth weight and adverse maternal outcomes of antepartum hemorrhage and oligohydramnios. We estimated relative risks (RRs) with 95% CIs using generalized linear models within a propensity score (PS) fine stratification weighted cohort that accounted for various potential confounders of maternal sociodemographic characteristics, comorbidities, co-medication use, and general markers of burden of illness. Of 1.8 million pregnancies in the PS weighted analyses, exposure to NSAIDs during early pregnancy was associated with slightly increased risks for neonatal outcomes of major congenital malformations (PS-adjusted RR, 1.14 [CI, 1.10 to 1.18]) and low birth weight (1.29 [1.25 to 1.33]), and for maternal outcome of oligohydramnios (1.09 [1.01 to 1.19]) but not antepartum hemorrhage (1.05 [0.99 to 1.12]). The risks of overall congenital malformations, low birth weight, and oligohydramnios remained significantly elevated despite comparing NSAIDs against acetaminophen or past users. Risks of adverse neonatal and maternal outcomes were higher with cyclooxygenase-2 selective inhibitors or use of NSAIDs for more than 10 days, whereas generally similar effects were observed across the three most frequently used individual NSAIDs. Point estimates were largely consistent across all sensitivity analyses, including the sibling-matched analysis. Main limitations of this study are residual confounding by indication and from unmeasured factors. Conclusions This large-scale, nationwide cohort study found that exposure to NSAIDs during early pregnancy was associated with slightly higher risks of neonatal and maternal adverse outcomes. Clinicians should therefore carefully weigh the benefits of prescribing NSAIDs in early pregnancy against its modest, but possible, risk of neonatal and maternal outcomes, where if possible, consider prescribing nonselective NSAIDs for

Abstract Background Preeclampsia is a major cause of maternal and perinatal mortality and morbidity. The etiology of preeclampsia remains unclear. Recently, it was shown that misregulation of fms-like tyrosine kinase-1 (Flt-1) in the peripheral blood mononuclear cells of pregnant women results in over-expression of the soluble splice variant of Flt-1, sFlt-1, producing an additional (extra-placental) source of sFlt-1 that can contribute to the etiology of preeclampsia. The aim of this study was to investigate the relationship between preeclampsia and a dinucleotide (threonine-glycine; TG)n repeat polymorphism in the 3' non-coding region of the Flt-1 gene. Methods The number of the d(TG)n repeats was analyzed in 170 patients with preeclampsia and in 202 normotensive pregnancies. The region containing the dinucleotide repeat polymorphism of the Flt-1 gene was amplified by polymerase chain reaction (PCR) from the DNA samples and was analyzed by direct PCR sequencing. Results We found 10 alleles of the dinucleotide repeat polymorphism and designated these as allele*12 (A1) through allele*23 (A12) according to the number of the TG repeats, from 12 to 23. The frequency of the 14-repeat allele (A3) was most abundant (63.82% in preeclampsia and 69.06% in controls), followed by the 21-repeat allele (A10; 28.53% in preeclampsia and 23.76% in controls). There was no significant difference in the allele frequency between patients with preeclampsia and normal controls. The most common genotype in preeclamptic and normotensive pregnancies was heterozygous (TG)14/(TG)21 (41.76%) and homozygous (TG)14/(TG)14 (45.05%), respectively. However, the genotype frequencies were not significantly different between preeclamptic patients and controls. Conclusion This is the first study to characterize the dinucleotide repeat polymorphism of the Flt-1 gene in patients with preeclampsia. We found no differences in the allele or genotype frequencies between patients with preeclampsia and normal pregnancies. Although limited by a relatively small sample size, our study suggests that the d(TG)n repeat polymorphism of the Flt-1 gene is not associated with the development of preeclampsia in Korean pregnant women.

Oral corticosteroids (OCS) are frequently used during pregnancy, but patterns of their usage and indications are understudied. We described OCS utilization among pregnant women in South Korea using the Health Insurance Review and Assessment database, 2010-2021. Among 4,574,294 pregnancies, 6.2% (n = 283,001) were exposed to OCS, with the annual prevalence increasing from 4.98% in 2010 to 6.65% in 2021. Methylprednisolone and prednisolone accounted for 90% of OCS use during pregnancy, and the median duration of prescriptions was four days. Respiratory and skin diseases were the most common indications, and prescriptions for pregnancy-associated conditions increased notably after 2017, coinciding with insurance coverage for infertility treatments. OCS prescriptions declined during the first trimester and increased near delivery, suggesting discontinuation upon pregnancy recognition. Our findings highlight the common and increasing use of OCS during pregnancy, mainly for acute conditions, underscoring the need for further research on their safety in pregnant populations., Competing Interests: Ju-Young Shin received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of South Korea, and pharmaceutical companies, including Pfizer, UCB, and LG Chem, outside the submitted work., (© 2025 The Korean Academy of Medical Sciences.)

There is a growing interest in using artificial intelligence (AI) technology to obtain information on the risk and safety of drugs in pregnancy. Inadvertent drug exposure in pregnant women is inevitable in acute or chronic diseases, especially in unplanned pregnancies. According to the Korean mother safe counselling center database (2010-2023), many Korean pregnant women and their families asked about the teratogenicity of their exposed drugs. The most frequently used drug was topiramate (n=2,018), followed by isotretinoin (n=1,972), dexamethasone (n=1,279), and doxycycline (n=1,119). Unexpectedly, thalidomide, a notorious teratogen that causes phocomelia, was included. It has been withdrawn from general prescriptions since 1961, except for the treatment of multiple myeloma. Her partner used it for the treatment of multiple myeloma. In this study, we evaluated the usefulness of AI Chat generative pretrained transformer (Chat GPT) by comparing information between AI and a literature review on isotretinoin, a well-known teratogen to which Korean pregnant women are frequently exposed. Chat GPT provides general information on teratogenicity for pregnant women and medical providers rather than on their exposure. Thus, AI can induce unnecessary termination of pregnancy due to misinformation and misperception in cases of notorious teratogens such as isotretinoin. Therefore, counseling on the teratogenicity of medication exposure in pregnancy must be performed with Chat GPT, as well as a literature review. Further studies are required to obtain more individualized information using AI in the field of teratology.

Objective: This study aimed to evaluate the prevalence of urinary incontinence (UI) and its associated risk factors among pregnant Korean women, as UI significantly impacts their quality of life., Methods: A cross-sectional study involving singleton pregnant women was conducted between April and December 2023. Data were collected using a questionnaire assessing demographic information and UI symptoms. The International Consultation on Incontinence Questionnaire-UI short form was used to diagnose UI., Results: A total of 824 pregnant women from three centers participated, with an overall prenatal UI prevalence of 40.2% (331/824). Stress UI was most common (77.1%), followed by mixed UI (16.9%), and urgency UI (6.0%). Risk factors for UI included prior delivery mode, specifically vaginal delivery (adjusted odds ratio [aOR], 5.61; 95% confidence interval [CI], 1.40-22.50; P=0.015) and combined vaginal and cesarean delivery (aOR, 23.14; 95% CI, 1.77-302.74; P=0.017). Additionally, second trimester (aOR, 1.99; 95% CI, 1.19-3.32; P=0.009) and third trimester (aOR, 4.44; 95% CI, 2.65-7.40; P<0.001) were associated with increased UI risk. Conversely, drinking alcohol before pregnancy was a protective factor (aOR, 0.72; 95% CI, 0.53-0.99; P=0.046)., Conclusion: Approximately 40% of Korean pregnant women experience prenatal UI. Prior delivery mode and advanced gastrointestinal age are significant risk factors. Further research with postpartum and long-term follow-ups is needed.

Background: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy., Methods: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model., Results: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy., Conclusion: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded., Competing Interests: The authors declare no potential conflict of interest relevant to this study. Ju-Young Shin received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of South Korea, and pharmaceutical companies, including LG chem, UCB, and Pfizer, outside the submitted work., (© 2024 The Korean Academy of Medical Sciences.)

Purpose: The purpose of this study was to explore the meaning of pregnant women's experiences with drinking alcohol during first trimester of pregnancy., Methods: The data were collected through in-depth interviews of 7 pregnant women who drank alcohol in the first trimester. Giorgi's phenomenological method was used for data analysis., Results: Findings included 6 main themes and 14 themes. The main themes concerning pregnancy and drinking were: 'Open attitude in drinking, History of drinking in family or spouse, Seeking information in how drinking affects pregnancy, Regret not doing planned pregnancy and not quitting drinking before pregnancy, Willing to stop drinking until the child birth, Awareness about importance of preconception care., Conclusion: The results of this study provide a deeper understanding of pregnant women's experiences of drinking alcohol during the first trimester of pregnancy. These results can be used in the development of strategies to prevent drinking alcohol during first trimester and to support preconception care and prenatal care.

Objective: To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells., Methods: A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group., Results: No differences were found between the two groups' mean plasma homocysteine levels (7.6±1.5 µmol/L vs. 7.1±2.1 µmol/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant (7.7±1.1 µmol/L) had higher homocysteine levels than those with the CC and CT variants (7.4±1.9 µmol/L and 7.4±1.2 µmol/L) and those with the CT variant (19.2±8.1%) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants (17.7±6.6% and 17.9±7. 0%), but the results of both comparisons were statistically insignificant., Conclusion: These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.

Objective: We aimed to investigate the factors associated with a positive intake of folic acid (FA) during the periconceptional period among Korean women., Design: In a cross-sectional study of demographic, obstetric and socio-economic data, history of periconceptional intake of FA and awareness of the benefits of FA supplementation in pregnancy were obtained and analysed using the chi2 test, followed by multiple logistic regression analysis., Setting: The Maternity School, Cheil General Hospital and Women's Healthcare Center, Seoul, South Korea, between October 2005 and March 2006., Subjects: In total 1313 pregnant women participating in a two-day training course available every month., Results: After excluding subjects with incomplete or inconsistent data, there were 1277 women included in the analysis. Participants were aged 29.4 (sd 2.9) years and had a mean gestational age of 27.9 (sd 7.1) weeks. Only 131 (10.3 %) women took FA during the periconceptional period. According to multiple logistic regression analyses, the adjusted OR for FA supplementation was 1.79 (95 % CI 1.10, 2.91) in women who had previous spontaneous abortions, 4.10 (95 % CI 2.43, 6.78) in women who planned their pregnancy and 6.63 (95 % CI 2.08, 21.12) in those who were aware of the protective effects of FA., Conclusions: Periconceptional intake of FA was more likely among Korean women with a history of previous spontaneous abortion, who planned their pregnancy or who were aware of the protective effects of FA during pregnancy. However, the proportion of women who took FA in the periconceptional period was low.

Sophrology, based on a combination of Western relaxation therapy and Eastern yoga and meditation might decrease maternal stress during labor. This study aimed to evaluate whether prenatal sophrologic childbirth preparation may decrease maternal and neonatal adverse response associated with delivery. In a nested case-control study, 69 nulliparous, singleton pregnant women who underwent an educational course of sophrologic childbirth preparation were compared to 69 nulliparous, singleton, age- and gestational age-matched pregnant women who did not receive any childbirth preparation. All babies were vaginally delivered. Groups were not different (P > 0.05) in the number of neonates born with meconium-stained amniotic fluid as well as in the number of babies with Apgar score < or = 7 at 1 and 5 minutes after birth. Duration of labor was not different between groups. The number of women requiring oxytocin and delivering babies with low pH blood levels tended to be lower in the group undergoing sophrologic childbirth preparation, i.e. 58.0% vs 72.5% (P = 0.07) and 1.4% vs 10.9% (P = 0.06), respectively. In conclusion, we were unable to confirm that prenatal sophrologic childbirth preparation has a definitive role in decreasing adverse maternal and fetal response to pain or in shortening labor. Prospective cohort studies with a larger sample size or randomized trials may help to clarify this gap.