Usefulness and limitations of Chat GPT in getting information on teratogenic drugs exposed in pregnancy

Article information

Obstet Gynecol Sci. 2025;68(1):1-8
Publication date (electronic) : 2024 November 20
doi : https://doi.org/10.5468/ogs.24231
1Korean MotherSafe Counselling Center, Pregnancy & Breastfeeding Medicines Information Center, Seoul, Korea
2Department of Obstetrics and Gynecology, Inje University Ilsan Paik Hospital, Goyang, Korea
Corresponding author: Jung Yeol Han, MD, PhD Department of Obstetrics and Gynecology, Inje University Ilsan Paik Hospital, 170 Juhwa-ro, Ilsanseo-gu, Goyang 10380, Korea E-mail: hanjungyeol055@gmail.com
Received 2024 August 26; Revised 2024 October 13; Accepted 2024 November 3.

Abstract

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 It has been withdrawn from general prescriptions since 1961, except for the treatment of multiple myeloma.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.

Introduction

Artificial intelligence (AI) technology is incorporated to assist informed decision-making processes in healthcare settings.

Developed by OpenAI (Open AI Inc, San Francisco, CA, USA), chat generative pretrained transformer (Chat GPT) is a large language model. Chat GPT4 employs one trillion parameters and can comprehend and construct longer and more intricate sentences. The ability of Chat GPT4 to retain more contextual data in its memory makes it more intelligent [1].

Studies have shown the potential of Chat GPT in assisting informed decision-making by healthcare providers [2-4]. Chat GPT analyzes written materials fed into neural networks [5,6].

This AI technology understands and responds to conversational input in a human-like manner.

Therefore, AI technology can be incorporated to assist in informed decision-making processes in teratology information services for pregnant women and their medical providers.

Almost all pregnant women are exposed to various medications due to unintended pregnancies and chronic illnesses [7,8].

Some drugs are known as significant teratogens [9,10]. Pregnant women exposed to drugs are concerned about their uncertain teratogenic risks. Some pregnant women select termination of pregnancy due to misinformation and misconceptions about drugs exposed in pregnancy, even non-teratogenic drugs. Meanwhile, other pregnant women opt to terminate pregnancy owing to substantial risk following exposure to known teratogenic drugs. Our recent study has shown that the pregnancy termination rate was approximately 30% (92/317) after exposure to a well-known teratogen, isotretinoin [11].

Since 2010, the Korean mother safe counselling center, a type of teratology information service, has provided evidence-based information on the teratogenicity of drugs in pregnant women. The evidence is from the literature and a commercial reproductive database, Micromedex® (IBM, Armonk, NY, USA) [12].

On the other hand, in the field of teratology counseling or information, Chat GPT can help pregnant women and medical providers obtain information on the teratogenicity and fetotoxicity of drugs in pregnancy because of its easy accessibility.

Therefore, we aimed to evaluate the usefulness of Chat GPT in teratology counseling or information.

Exposure of teratogenic or fetotoxic drugs in Korean pregnant women

Table 1 shows the known teratogens or fetotoxic drugs [13] asked by Korean pregnant women at the Korean mother safe counselling center from 2010 to 2023.

Frequency of exposure to known teratogenic or fetotoxic drugs reported by Korean pregnant women, 2010-2023 [13]

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.

Many Korean pregnant women and their partners are exposed to known teratogens or fetotoxic drugs. Many pregnant women exposed to drugs and medical providers ask about the teratogenicity or fetotoxicity of drugs to obtain related information.

However, their accessibility and expertise may not be enough for more efficient decision-making in the field of teratology by literature review and a commercial reproductive toxicity database, Micromedex ® (IBM) [12].

Recently, Chat GPT, an AI technology, has been used for efficient decision-making in various fields.

Among the known teratogenic and fetotoxic drugs, isotretinoin is notoriously problematic. There were approximately one million prescriptions for acne in Korea in 2022. Our recently published study showed that approximately 30% of pregnant women exposed to isotretinoin chose pregnancy termination [11].

Is Chat GPT useful for decision-making between continuing and terminating pregnancies with isotretinoin exposure during pregnancy?

A pregnant woman exposed to isotretinoin

A pregnant woman, 35 years old, gravida 2, artificial abortion 1, at 6 weeks of gestation, was exposed to one capsule (10 mg) of isotretinoin per day for 5 days. She had taken a drug for the treatment of acne, not a severe form, 2 years before pregnancy. The final exposure was 3 weeks after conception. She was referred to our clinic for further information on teratogenicity after obtaining information from the Korean mother safe counselling center.

The information on the teratogenicity of this case is obtained using Chat GPT and literature review.

The evaluation of the teratogenicity of the embryo exposed to isotretinoin in this case was based on the type of birth defect, significance of birth defects, including structural abnormality and developmental disability, and percentage of birth defects. After that, it is compared between Chat GPT and a literature review. Chat GPT 4o was asked for information on teratogenicity of isotretinoin related to this case [14].

What birth defects or developmental disability have occurred by isotretinoin exposure until 5 weeks of gestation daily a capsule (10 mg) for 5 days?

Isotretinoin (commonly known by the brand name Accutane) is a powerful medication primarily used to treat severe acne. However, it is highly teratogenic, meaning it can cause significant birth defects if taken during pregnancy. Even short-term exposure during early gestation can be harmful. Here are the potential birth defects or developmental disabilities that can occur due to isotretinoin exposure up to 5 weeks of gestation. 1) Craniofacial abnormalities: this includes deformities of the face, ears, and palate (such as cleft palate). 2) Cardiovascular defects: malformations of the heart and blood vessels. 3) Central nervous system abnormalities: this can include hydrocephalus (excess fluid in the brain), microcephaly (small head size), and other neurological impairments. 4) Thymus gland abnormalities: underdevelopment or absence of the thymus gland, which is crucial for immune system function. 5) Eye abnormalities: such as microphthalmia (abnormally small eyes), anophthalmia (absence of one or both eyes), and other visual impairments. And 6) developmental delays and intellectual disabilities: due to central nervous system abnormalities and other factors.

Even short-term exposure to isotretinoin during early pregnancy (within the first few weeks of gestation) can result in these serious congenital malformations.

How significant are birth defects or developmental disabilities by isotretinoin exposed until 5 weeks of gestation daily a capsule (10 mg) for 5 days?

Isotretinoin, commonly known as accutane, is a potent teratogen, meaning it can cause significant birth defects or developmental disabilities when exposure occurs during pregnancy. The risk of teratogenic effects is particularly high if the drug is taken during the critical period of organogenesis, which typically spans from the 3 to the 8 weeks of gestation. Significance of exposure until 5 weeks of gestation. 1) Early gestation exposure (first 5 weeks). During the first 2 weeks post-conception (~2 weeks of gestation), the conceptus is generally considered in a pre-implantation stage. Exposure to teratogens during this time is often thought to result in an “all-or-nothing” effect, meaning it either results in no effect or leads to a miscarriage. By 3-5 weeks of gestation, the embryo enters a critical period of development where the risk of teratogenic effects from isotretinoin is high. Exposure during this period can lead to severe birth defects because major organ systems are beginning to form. 2) Potential birth defects. Central nervous system (CNS) abnormalities: hydrocephalus, microcephaly, and intellectual disabilities. Craniofacial abnormalities: cleft palate, ear malformations, and facial dysmorphia. Cardiovascular defects: conotruncal heart defects, septal defects. And thymic abnormalities: hypoplasia or aplasia of the thymus. 3) Developmental disabilities. Intellectual disabilities and developmental delays can result from CNS damage. Behavioral issues and learning disabilities may also be present. 4) Risk assessment. The risk of birth defects and developmental disabilities increases significantly with any exposure to isotretinoin during pregnancy. Even a short course of isotretinoin (10 mg daily for 5 days) during the critical period can pose a substantial risk. Isotretinoin is classified as a category X drug by the Food and Drug Administration (FDA), indicating that it is contraindicated in pregnancy due to its high teratogenic potential. And 5) recommendations. Women of childbearing potential must use effective contraception and avoid pregnancy during and for at least one month after discontinuing isotretinoin therapy. If pregnancy occurs while taking isotretinoin, immediate consultation with a healthcare provider is essential for risk assessment and management options. Given the critical nature of the period up to 5 weeks of gestation and the potent teratogenic effects of isotretinoin, the risk of significant birth defects and developmental disabilities is high if exposure occurs during this time.

What percent is the rate of birth defects in pregnancy exposed to isotretinoin until 5 weeks of gestation daily a capsule (10 mg) for 5 days?

The use of isotretinoin during pregnancy, even for a short duration, poses a significant risk of birth defects. Isotretinoin is known to be highly teratogenic (can cause birth defects). Studies indicate that the risk of major congenital malformations is as high as 20% to 30% when exposed to isotretinoin during pregnancy, especially during the first trimester, which is the critical period for fetal development.

In your case, isotretinoin exposure occurred daily for 5 days during the first 5 weeks of gestation. While specific data for a precise dose and short exposure period like this (10 mg/day for 5 days) might be less studied, even short-term exposure during early pregnancy carries a risk. Malformations typically affect the central nervous system, heart, face, and thymus.

Given that the fetus’s organogenesis starts early, exposure within the first 5 weeks of gestation can still result in a significant risk of birth defects. As a general rule, any isotretinoin exposure during pregnancy is considered dangerous and warrants immediate consultation with a healthcare provider for risk assessment and guidance.

If you are facing such a situation, discussing it with your doctor is crucial for personalized medical advice and potential interventions.

Literature review: information on the teratogenicity of isotretinoin

The critical period for isotretinoin is from the second week to the fifth week after conception [15]. A major mechanism of isotretinoin teratogenesis is its deleterious effect on cephalic neural-crest cell activity, which results in craniofacial, cardiac, and thymic malformations [16].

A systematic review of teratogenicity caused by isotretinoin exposure in pregnancy showed that the rate of congenital malformation weighted by the number of participants in 10 studies was 15% (95% confidence interval [CI], 9 to 23) in Fig. 1. [17].

Fig. 1.

Random-effects single-arm meta-analysis of major malformation prevalence after isotretinoin exposure reported by the 10 included studies [17]. IV, inverse variance; CI, confidence interval.

The rate differed before 2006 and after 2006. The rate before 2006 was higher than after 2006.

In the meta-analysis, odds ratios of congenital malformations in the birth of pregnant women exposed to isotretinoin with subgroup analysis of the studies published before vs. after 2006 were 33.78 (95% CI, 16.12 to 70.82) and 3.76 (95% CI, 0.13 to 110.35), respectively in Fig. 2.

Fig. 2.

Meta-analysis of odd ratios: major congenital malformations in offspring of isotretinoin-exposed women with subgroup analysis of the studies published before versus after 2006 [17]. M-H, mantelhaenszel test; CI, confidence interval; Mal., malformation.

The authors have discussed this difference. This difference may be explained by the smaller doses and possibly the shorter duration of isotretinoin exposure during pregnancy. In terms of the exposure dose, the highest dose was up to 87.3 mg/day before 2006 and only 43.7 mg/day after 2006. Regarding the duration of isotretinoin exposure during pregnancy, the last dose before 2006 was up to 10 weeks after conception, compared with 30 days of gestation after 2006.

In contrast, we reported a study on pregnancy outcomes of 151 isotretinoin exposures with 682 non-isotretinoin exposures as controls from the Korean mother-safe counselling call center database (2001-2017). The rates of major congenital malformations were 4.8% (2/51) and 3.2% (20/676), respectively (P=0.596) in Table 2 [10].

Rate of malformations between isotretinoin exposure and non-exposure groups [10]

Additionally, in Germany, Schaefer et al. [18] reported isotretinoin exposure and pregnancy outcomes. Of 18 live births, including one pair of twins, one major birth defect (small ventricular septal defect) was observed. No infants exhibited any symptoms of retinoid embryopathy. 

Recently, our group reported a nationwide population-based study on adverse pregnancies and child outcomes of oral retinoids, including isotretinoin-exposed pregnancies [19]. Of the 3,894,184 pregnancies, 720 pregnancies (0.02%) were identified as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for the oral retinoid-exposed group and 357.9 per 10,000 births for the unexposed group, and the weighted relative risk was 1.10 (95% CI, 0.65-1.85) in the oral retinoid-exposed group compared with that in the unexposed group.

In terms of long-term outcomes, Adams and Lammer [20,21] showed that in addition to intellectual deficits accompanied by frank brain malformation and other physical manifestations of isotretinoin embryopathy, intellectual deficits could also be induced in children without physical signs of abnormal development. In animal neurobehavioral teratology studies, rodents and songbirds exposed to retinoids exhibit behavioral dysfunction [22] and learning and memory deficits [23].

Additionally, our recent report showed that the rates of neurodevelopmental delay and suspected autism spectrum disorder were 4.7% (10/214) and 1.9% (4/214), respectively, in the follow-up period of 0.5-180 months of children delivered after in utero exposure to isotretinoin [11].

In addition, in our nationwide population-based study, the oral retinoid-exposed group had a higher incidence rate of autism spectrum disorders (20.9 vs. 9.1 per 10,000 personyears) and intellectual disabilities (18.8 vs. 6.8 per 10,000 person-years) than the unexposed group. Before applying matching weights, significantly increased risk in autism spectrum disorder (crude hazard ratio [HR], 2.32; 95% CI, 1.25-4.31) and intellectual disability (2.76 to 1.44-5.30) were observed. After applying matching weights, the HR was attenuated to 1.63 (0.60-4.41) for autism spectrum disorder and 1.71 (0.60-4.93) for intellectual disorder [19].

In summary of the literature review, the average rate of congenital malformations in pregnant women exposed to isotretinoin was 15% (range, 0-28%). The rate of neurobehavioral dysfunction was 0.2% to 50%.

Comparison between Chat GPT and literature review

Information from Chat GPT on teratogenicity in pregnant women exposed to isotretinoin for approximately 5 weeks includes potential birth defects or developmental disabilities that can occur because of isotretinoin exposure up to 5 weeks of gestation: structural malformations such as craniofacial abnormalities, cardiovascular defects, CNS abnormalities, thymus gland abnormalities, and eye abnormalities. Developmental delays and intellectual disabilities were also included. In addition, Chat GPT shows that the effects according to exposure time in pregnancy vary from all or nothing in the first 2 weeks post-conception to severe birth defects at 3-5 weeks in post-conception 3 weeks to 8 weeks. In the risk assessment, the risk of birth defects and developmental disabilities increased significantly with exposure to isotretinoin during pregnancy. Even a short course of isotretinoin (10 mg daily for 5 days) during the critical period can pose a substantial risk. Isotretinoin is classified as a category X drug by the FDA, indicating that it is contraindicated in pregnancy because of its high teratogenic potential. Finally, as recommended, women of childbearing potential must use effective contraception and avoid pregnancy during and for at least 1 month after discontinuing isotretinoin therapy. If pregnancy occurs while taking isotretinoin, immediate consultation with a healthcare provider is essential for risk assessment and management. In addition, given the critical nature of the period of up to 5 weeks of gestation and the potent teratogenic effects of isotretinoin, the risk of significant birth defects and developmental disabilities is high if exposure occurs during this time.

On the other hand, in the literature review, beyond the contents described by Chat GPT, studies showed that the rate of congenital malformation was an average of 15% (range, 0-28%) in pregnant women exposed to isotretinoin. The rate of neurobehavioral dysfunction is 0.2% to 50%. The literature review shows the rates of congenital malformation and neurobehavioral dysfunction following exposure dose, gestational age during exposure to isotretinoin, study types including prospective cohort studies, nationwide population studies, and systematic reviews with meta-analyses, years of publication of the studies, and study participants from many countries, including Korean pregnant women.

A literature review can help pregnant women obtain individualized information for informed decision-making to continue or stop their pregnancy.

Usefulness and limitations of Chat GPT

Chat GPT may be useful for patients and medical providers who want to obtain information on the teratogenicity of medications, including teratogenic or fetotoxic drugs such as isotretinoin.

However, it has some limitations in the field of teratology information. First, information on Chat GPT is less individualized. Pregnant women exposed to medications want to obtain much more detailed information regarding the dose, duration, and gestational time of exposure due to their fear of adverse pregnancy outcomes, including congenital malformations, and long-term outcomes, including intellectual deficits.

Second, Chat GPT showed a high rate of congenital malformations. However, the literature shows that the average rate of congenital malformation is 15% (range, 0-28%) when digits are used in pregnancies exposed to isotretinoin. Additionally, these rates were different from those reported in other studies.

Third, Chat GPT only shows developmental disabilities, including intellectual disabilities and developmental delays, and learning disabilities as long-term outcomes after exposure at 5 weeks of gestation. However, the literature shows that the rate of neurobehavioral dysfunction ranges from 0.2% to 50%. This finding also differs from the results of other studies.

Fourth, Chat GPT uses incorrect terminology. For example, Chat GPT shows a critical period of organogenesis, which typically spans from the 3 weeks to the 8 weeks of gestation. However, from weeks 3 to 8, the embryonic period is the correct period for organogenesis. During week 3, gastrulation occurred, establishing 3 distinct cell layers: the mesoderm, endoderm, and ectoderm. By the end of week 8, the organ systems had developed and were ready for further maturation. From week 9, the fetal period begins, which involves the growth and differentiation of anatomical structures and lasts until birth [24].

Finally, Chat GPT can induce unnecessary termination of pregnancy owing to misinformation in its training data, and misperception causes excessive fear of teratogenicity by less individualizing information and lack of sufficient clinical validation.

Conclusion

Our study showed that Korean pregnant women are exposed to various teratogenic or fetotoxic drugs.

Although Chat GPT, an AI technology, has the potential for more efficient decision-making in the field of teratology, it provides only general information on teratogenicity for patients and medical providers rather than individually. Thus, Chat GPT can induce unnecessary termination of pregnancy owing to misinformation and misperception of teratogenicity. Therefore, counseling on the teratogenicity of medication exposure in pregnancy must be performed with Chat GPT, along with a literature review.

Further studies are required to obtain more individualized information using AI in the field of teratology.

Notes

Conflict of interest

The author declares no conflict of interest.

Ethical approval

None.

Patient consent

None.

Funding information

None.

References

1. OpenAI. Introducing ChatGPT [Internet]. San Francisco (CA): Open AI Inc; c2023. [cited 2023 Jan 1]. Available from: https://openai.com/blog/chatgpt.
2. Sallam M. ChatGPT utility in healthcare education, research, and practice: systematic review on the promising perspectives and valid concerns. Healthcare (Basel) 2023;11:887.
3. Biswas SS. Role of chat GPT in public health. Ann Biomed Eng 2023;51:868–9.
4. Kim JH, Kim SK, Choi J, Lee Y. Reliability of ChatGPT for performing triage task in the emergency department using the Korean triage and acuity scale. Digit Health 2024;10:20552076241227132.
5. DiGiorgio AM, Ehrenfeld JM. Artificial intelligence in medicine & ChatGPT: de-tether the physician. J Med Sys 2023;47:32.
6. Johnson SB, King AJ, Warner EL, Aneja S, Kann BH, Bylund CL. Using ChatGPT to evaluate cancer myths and misconceptions: artificial intelligence and cancer information. JNCI Cancer Spectr 2023;7:pkad015.
7. Han JY, Nava-Ocampo AA, Koren G. Unintended pregnancies and exposure to potential human teratogens. Birth Defects Res A Clin Mol Teratol 2005;73:245–8.
8. Vuignier Y, Beaud F, Kosinski C, Panchaud A, Lebon S, Baud D, et al. Exposure to alirocumab during the first trimester of pregnancy: a case report. Birth Defects Res 2021;113:1156–60.
9. Abdulaziz HM, Shemies RS, Taman M, Mosbah A, Elkannishy G. Fetal proximal and distal limb anomalies following exposure to mycophenolate mofetil during pregnancy: a case report and review of the literature. Lupus 2021;30:1522–5.
10. Cha EH, Kim N, Kwak HS, Han HJ, Joo SH, Choi JS, et al. Pregnancy and neonatal outcomes after periconceptional exposure to isotretinoin in Koreans. Obstet Gynecol Sci 2022;65:166–75.
11. Lee YR, Hwang DW, Chun KC, Kim YA, Koh JW, Han JY, et al. Termination of pregnancy following periconception isotretinoin exposure in South Korea. Clin Exp Obstet Gynecol 2024;51:144.
12. Micromedex®. Introducing Micromedex® [Internet]. Armonk (NY): Micromedex®; c2024. [cited 2024 May 5]. Available from: https://www.micromedexsolutions.com/home/dispatch/CS/1A2735/PFActionId/pf.HomePage.
13. Cunningham FG, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, et al. Williams obstetrics 25th edth ed. New York (NY): Mcgraw-hill; 2014.
14. ChatGPT 4o. Isotretinoin pregnancy risks [Internet]. San Francisco (CA): Open AI Incc; c2024. [cited 2024 May 5]. Available from: https://chatgpt.com/share/081642f7-c512-4653-af20-0061e5209ff9.
15. AlGhamdi KM, Khurram H, Asiri YA, Mandil A. Dermatologists’ level of compliance with the prescription guidelines of isotretinoin for females of childbearing potential. Int J Dermatol 2011;50:1094–8.
16. Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, et al. Retinoic acid embryopathy. N Engl J Med 1985;313:837–41.
17. Choi EJ, Kim N, Kwak HS, Han HJ, Chun KC, Kim YA, et al. The rates of major malformations after gestational exposure to isotretinoin: a systematic review and metaanalysis. Obstet Gynecol Sci 2021;64:364–73.
18. Schaefer C, Meister R, Weber-Schoendorfer C. Isotretinoin exposure and pregnancy outcome: an observational study of the Berlin Institute for clinical teratology and drug risk assessment in pregnancy. Arch Gynecol Obstet 2010;281:221–7.
19. You W, Choi A, Lee H, Han JY, Lee JH, Shin JY. Adverse pregnancy and child outcomes in oral retinoid-exposed pregnancies: a nationwide population-based study. J Korean Med Sci 2024;39e201.
20. Adams J, Lammer EJ. Relationship between dysmorphology and neuro-psychological function in children exposed to isotretinoin ‘in utero’. In : Fujii T, Boer GJ, eds. Functional neuroteratology of short term exposure to drugs 1st edth ed. Tokyo: Teikyo University Press; 1992. p. 159–70.
21. Adams J, Lammer EJ. Neurobehavioral teratology of isotretinoin. Reprod Toxicol 1993;7:175–7.
22. Adams J. Structure-activity and dose-response relationships in the neural and behavioral teratogenesis of retinoids. Neurotoxicol Teratol 1993;15:193–202.
23. Olson CR, Mello CV. Significance of vitamin A to brain function, behavior and learning. Mol Nutr Food Res 2010;54:489–95.
24. Rehman B, Muzio MR. Embryology, week 2-3 [Internet]. Treasure Island (FL): StatPearls Publishing; c2023. [cited 2023 May 1]. Available from: https://pubmed.ncbi.nlm.nih.gov/31536285/.

Article information Continued

Fig. 1.

Random-effects single-arm meta-analysis of major malformation prevalence after isotretinoin exposure reported by the 10 included studies [17]. IV, inverse variance; CI, confidence interval.

Fig. 2.

Meta-analysis of odd ratios: major congenital malformations in offspring of isotretinoin-exposed women with subgroup analysis of the studies published before versus after 2006 [17]. M-H, mantelhaenszel test; CI, confidence interval; Mal., malformation.

Table 1.

Frequency of exposure to known teratogenic or fetotoxic drugs reported by Korean pregnant women, 2010-2023 [13]

Teratogenic or fetotoxic drug Frequency
Topiramate 2,018
Isotretinoin 1,972
Corticosteroids: dexamethasone 1,279
Doxycycline 1,119
Fluconazole 796
Paroxetine 349
Valproic acid 186
Tretinoin 163
Tetracycline 151
Methotrexate 126
Lithium 118
Methimazole 114
Carbamazepine 110
Misoprostol 79
Angiotensin receptor blockers: valsartan 67
Lamotrigine 58
Angiotensin converting enzyme inhibitors: enalapril 49
Acitretin 34
Mycophenolate 20
Leflunomide 18
Phenobarbital 17
Androgens: testosterone 12
Ribavirin 12
Phenytoin 10
Tamoxifen 9
Warfarin 8
Cyclophosphamide 6
Lenalidomide 2
Danazol 2
Thalidomide 1

Table 2.

Rate of malformations between isotretinoin exposure and non-exposure groups [10]

Variable Non-exposure group (n=676) Exposure group (n=51) Odds ratio (95% CI) P-valuea
Spontaneous abortion 59 (8.7) 9 (17.6) 2.022 (1.065-3.839) 0.035
Live birth 617 (91.3) 42 (82.4)
Total malformations 104 (16.9) 7 (16.7) 0.989 (0.492-1.988) 0.975
Major malformations 20 (3.2) 2 (4.8)b 1.469 (0.355-6.075) 0.596
Minor malformations 84 (13.6) 5 (11.9)c 0.874 (0.375-2.038) 0.754

Values are presented as number (%) unless otherwise indicated.

CI, confidence interval.

a

Chi-squared test;

b

ventricular septal defect (n=1), postaxial polysyndactyly with a curling toe on the left foot and bilateral preauricular skin tags (n=1);

c

nasolacrimal duct obstruction (n=1), skin tag on the right ear (n=1), dolicocephalic head (n=1), dimple in the left lower leg (n=1), and albinism with brown hair (n=1).