Teratogen Exposure Research Articles

Chemical-induced heart defects using a transgenic zebrafish model.

Congenital heart defects (CHDs) are common birth defects attributed to genetic and environmental factors such as pharmaceuticals and chemicals. Identifying modifiable environmental factors and understanding their impact on heart development is crucial for mitigating chemical-induced CHDs. Given the increasing number of chemical agents, efficient high-throughput systems are essential to evaluate their teratogenic potential during cardiovascular development, which is a major concern for chemical safety. In this study, we developed three transgenic zebrafish reporter lines, myl7: EGFP, kdrl: MRFP and gata1: MKate2, which enable real-time visualization of myocardial and endocardial development and cardiac function based on blood flow. These transgenic embryos were used to investigate the teratogenic effects of chemicals well known to induce heart defects in mammals, including humans. Our real-time imaging revealed that the teratogens induced significant malformations in cardiac morphogenesis, including abnormal heart tube formation, incomplete cardiac looping, and reduced heart chamber size. These teratogens also disrupted the expression of cardiac progenitor markers, suggesting impaired cardiac progenitor development. These defects were detected at the early stages (4-48 hours post-fertilization), suggesting that the stages of progenitor development to heart looing were most susceptible to teratogen exposure, ie the critical period for teratogen-induced heart defects. Functional defects, such as impaired blood flow, were observed using real-time imaging of the gata1-reporter line. This study demonstrates the utilization of transgenic zebrafish embryo models for high-throughput teratogenicity testing, which also allows us to analyze the mechanisms underlying chemical-induced heart defects. Therefore, our zebrafish models would contribute to the identification and reduction of risks associated with CHDs.

Frequency of Miscarriage in Newly Married Females Due to Teratogenic Drugs i.e. Selective Serotonin Reuptake Inhibitors and Anti-Epileptics

Background: Miscarriage is still a major reproductive health issue, particularly in areas where access to specialized treatment is scarce. In particular, newlywed women who might not be aware of the dangers of pharmaceuticals like selective serotonin reuptake inhibitors (SSRIs) and antiepileptic drugs (AEDs) may be at risk for teratogenic drug exposure during the early stages of pregnancy. Objective: The purpose of this study is to determine the rate of miscarriages among newlywed women in Quetta who were exposed to SSRIs and AEDs during the early stages of pregnancy. Methods: One hundred and twenty pregnant women in their first trimester who were enrolled at a tertiary care hospital participated in this qualitative study. The participants' exposure to antiepileptic medications (AEDs) or SSRIs was evaluated. With an emphasis on fetal outcomes, data were gathered via medical records and structured interviews. Prior to starting the data collection process, ethical permission was acquired. Results: Thirty-five (29.2%) of the 120 participants were exposed to SSRIs, twenty-five (20.8%) to AEDs, and sixty (50%) did not. Five (20%) of the AED group had fetal abnormalities, compared to six (17.1%) of SSRI users. There were just two (3.3%) abnormalities in the group that were not exposed, suggesting that medication exposure increases risk. Conclusion: An increased risk of miscarriages was linked to early prenatal exposure to SSRIs and AEDs. Insufficient counselling emphasizes the necessity of increased knowledge and prenatal preparation to reduce drug-related hazards and enhance results for both the mother and the fetus.

Indications for fetal echocardiography: consensus and controversies among evidence-based national and international guidelines.

Fetal echocardiography (FE) is an indication-driven examination for pregnant women with a fetus at high risk for congenital heart disease (CHD). Several familial, maternal and fetal factors are reported to increase the risk of CHD. The aim of this study was to highlight the existing differences in recommended indications for FE among recently published guidelines and consensuses of experts. Guidelines and expert consensuses published from January 2008 to October 2023 were identified through a systematic literature search. FE guidelines and consensus statements were excluded if not written in the English language and if indications for FE were not reported. All familial, maternal and fetal risk factors for CHD reported in the consensuses and guidelines were listed and comparisons were made between documents. The agreement or disagreement for each risk factor between guidelines and consensuses was classified as: complete agreement (all analyzed documents reported the same indication); partial agreement (all documents considered a risk factor as an indication, but with inconsistency in its definition); or complete disagreement (inconsistency between documents for the considered risk factor as an indication). Six guidelines and expert consensuses that met the inclusion criteria were identified. Overall, a total of 17 risk factors were identified as an indication for FE. Complete agreement was reached for 3/17 (17.6%) risk factors, all of which are fetal risk factors (suspected CHD at the anomaly scan, presence of major fetal extracardiac abnormality and non-immune hydrops fetalis). Partial agreement was recorded for 8/17 (47.1%) risk factors (family history of CHD, increased nuchal translucency, multiple gestation, maternal diabetes mellitus, maternal phenylketonuria, maternal infection, maternal autoimmune disease and autoantibody positivity, and teratogen exposure). Complete disagreement was recorded for 6/17 (35.3%) risk factors (inherited genetic disease associated with CHD, fetal genetic anomaly, suspected abnormality of heart rate or rhythm, first-trimester sonographic markers of CHD, abnormality of umbilical cord and venous system, and use of assisted reproductive technology). Areas of controversy regarding which CHD risk factors warrant FE were greater in quantity than were the areas of consensus. An internationally standardized agreement would be valuable for physicians and guideline developers. For many risk factors, further evidence is needed to justify their use as an indication for FE. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

Are assisted reproductive technology pregnancies more likely to be exposed to teratogenic medication? A whole-population study.

Assisted reproductive technology (ART) pregnancies are at greater risk of birth defects than non-ART pregnancies. Teratogenic medication exposure is a potential cause of birth defects that has not been compared between ART and non-ART pregnancies. To determine whether the prevalence of exposure to teratogenic medicines during pregnancy varies by conception method (ART and three non-ART groups: ovulation induction (OI), subfertile untreated, and fertile naturally conceiving). We linked state and commonwealth datasets for all live and stillbirths (≥20 weeks) in Western Australia with a conception date ≥1 July 2012 and date of birth ≤31 December 2014. We calculated the prevalence of exposure to teratogenic medicines (Therapeutic Goods Association Category D/X) across conception groups for the: (i) first trimester, and (ii) second and third trimesters. We identified 2041 ART, 590 OI, 2063 subfertile and 52 987 fertile pregnancies (57 681). The overall prevalence of exposure to Category D/X medicines was 0.8% in the first trimester, and 0.7% in the second and third trimesters. Category X medicines exposure was <0.5% for all conception groups and trimesters. The first trimesters of ART and OI pregnancies were more often exposed to Category D medicines than subfertile and fertile pregnancies, (ART = 4.9%, OI = 2.0% vs subfertile = 1.3%, fertile = 0.6%) as were later trimesters (ART = 3.4%, OI = 1.4% vs subfertile = 0.9%, fertile = 0.6%). The overall prevalence of exposure to teratogenic medicines is low; however, exposure was greatest in pregnancies arising from ART and may be a modest contributing factor to the higher rate of birth defects observed among ART babies.

Management of Tessier No. 2 Facial Cleft Using Millard Technique with Zig- Zag Ad-vancement Flap: A Case Report

Introduction: Craniofacial cleft is a rare congenital disorder that affects facial and skull. development, with an incidence estimated between 1.4-4.9 per 100,000 births. This condition often results in significant complications such as feeding difficulties, impaired speech, hearing issues, and psychosocial challenges. Among craniofacial clefts, the oblique facial cleft, including Tessier No. 2 cleft, is the rarest and least documented. This cleft is characterized by specific soft and hard tissue deformities resulting from a failure of fusion among facial processes during embryonic development. Case: An 8-month-old female presented with a unilateral cleft of the lips, gums, and palate on the left side, accompanied by a Tessier No. 2 facial cleft. The patient's mother reported no history of teratogenic exposure or family history of clefts. Clinical examination revealed hypoplasia of the middle third of the nasal margin, a flattened lateral nose, a widened nasal bridge, and a deviated nasal septum. The patient was diagnosed with unilateral complete labiognatopalatoschizis accompanied by Tessier No. 2 cleft. Case Management: The patient was prepared for labioplasty under general anesthesia after meeting the "rules of ten" criteria (10 weeks old, 10 pounds, 10 grams/dl hemoglobin). The surgery was performed using the Millard technique with a zig-zag advancement flap to achieve optimal tissue coverage and symmetry. Postoperative care included antibiotics, pain management, and follow-up visits. At the 3-month follow-up, the surgical site showed good healing with no signs of infection or significant complications. Conclusion: Understanding the specific anatomy and pathophysiology of Tessier No. 2 clefts is essential for effective surgical planning and outcomes. The modified Millard technique provides satisfactory aesthetic and functional results, although challenges remain. Comprehensive postoperative management and long-term follow-up are crucial to monitor healing and address any complications. Further research and multidisciplinary.Keyword: Facial Cleft, Tessier 2, Millard Technique, Zig-zag Advancement Flap

Pregnancy protection in women of child-bearing age prescribed ACE inhibitors, ARBs or statins - A nationwide cohort study

Abstract Background Cardiometabolic disorders, including hypertension, type-2 diabetes, and hyperlipidemia are increasingly prevalent among younger people. Consequently, women of child-bearing age may be prescribed renin-angiotensin system (RAS) inhibitors and statins. Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known teratogens. Statins are considered possibly teratogenic. In Denmark, ACEIs and ARBs have a ‘Do not use’ recommendation in pregnancy while statins ‘Should not be used’ in pregnancy. Previous studies have reported widespread use of RAS inhibitors without concomitant contraception among women of child-bearing age. This study investigated the situation in Denmark. Purpose To examine prescribing patterns of RAS inhibitors and statins alongside use of concomitant contraception among women of child-bearing age in Denmark. Methods Using nationwide Danish registers, women aged 15–50 years initiating ACEIs, ARBs and statins during 1995–2021 were identified and use of concomitant contraception was evaluated. Contraception was categorized as oral pill, implant, intrauterine device (IUD), or non-use. The duration of protection was assumed to be 1 year for oral contraceptives, 2 years for implants and 4 years for IUDs. Where multiple types of contraceptives were retrieved by individual patients, they were categorized as taking the contraceptive retrieved most recently. Data on non-prescription contraceptives were unavailable, e.g., condoms. Women unable to conceive due to infertility were excluded. Results 79 547 women (median age: 44 years; [interquartile range (IQR): 39–47]) on ACEIs, 64 326 women (median age: 44 years [IQR: 38–48]) on ARBs, and 71 499 women (median age: 45 years [IQR: 40–48]) on statins were included (Figure 1). Correspondingly, 69.1%, 62.8%, and 73.5% were not on contraceptives when starting treatment. Among women prescribed contraception: 70.2%/56.2%/63.1% were on oral contraceptives, 25.3%/30.9%/26.6% had IUDs and 4.5%/12.9%/10.3% had implants, respectively (Figure 1). Younger patients aged 15–29 years were least likely to be unprotected with 41.8%/29.7%/33.4% being unprotected. Among women aged 25 to 35 years the percentage of unprotected women was 51.3%/41.1%/47.7%. Older patients were more likely to have IUDs. Conclusion Substantial numbers of women of child-bearing age were prescribed ACEIs, ARBs and statins from 1995–2021. Most were not prescribed contraceptives. The lack of prescribed pregnancy protection was prevalent even among the youngest women aged 15–29 years and women aged 25 to 35 years, who are the most likely to become pregnant—inferring a potential risk of teratogenic exposure during pregnancy (Figure 2). Subsequent studies should investigate the extent of exposure to ACEIs, ARBs, and statins during pregnancy and the impact of the exposure on pregnancy outcomes.Figure 1 Contraceptive useFigure 2 Study rationale

The Influence of Prenatal Vitamin use and Community Health Programs on Reducing Teratogenic Medication Exposure and Improving Perinatal Nutrition among African American Adolescents with Limited Access to Healthcare

This review paper examines the critical influence of prenatal vitamin use and community health programs on reducing teratogenic medication exposure and improving perinatal nutrition among African American adolescents with limited access to healthcare. African American adolescents face disproportionate barriers to healthcare access, including socioeconomic challenges and systemic healthcare inequities, which contribute to heightened risks of teratogenic exposure and poor prenatal nutrition. The paper explores the role of prenatal vitamins such as folic acid, iron, and calcium in preventing congenital disabilities and enhancing maternal health. It also highlights the impact of community-based health programs and education initiatives that aim to bridge healthcare gaps for vulnerable populations. By focusing on adolescent pregnancy in African American communities, this review identifies key challenges such as limited healthcare access, inadequate educational resources, and socio-economic constraints. Furthermore, the paper assesses the effectiveness of current health interventions and policies, offering recommendations for improving healthcare access and expanding community programs. The review underscores the necessity for long-term research to address gaps in the intersection of race, adolescent health, and prenatal care, ultimately aiming to inform policy and program development that promotes equitable maternal and fetal health outcomes.

The Grenada Learning and Memory Scale: Psychometric features and normative data in Caribbean preschool children.

Neuropsychological assessment of preschool children is essential for early detection of delays and referral for intervention prior to school entry. This is especially pertinent in low- and middle-income countries (LMICs), which are disproportionately impacted by micronutrient deficiencies and teratogenic exposures. The Grenada Learning and Memory Scale (GLAMS) was created for use in limited resource settings and includes a shopping list and face-name association test. Here, we present psychometric and normative data for the GLAMS in a Grenadian preschool sample. Typically developing children between 36 and 72 months of age, primarily English speaking, were recruited from public preschools in Grenada. Trained Early Childhood Assessors administered the GLAMS and NEPSY-II in schools, homes, and clinics. GLAMS score distributions, reliability, and convergent/divergent validity against NEPSY-II were evaluated. The sample consisted of 400 children (190 males, 210 females). GLAMS internal consistency, inter-rater agreement, and test-retest reliability were acceptable. Principal components analysis revealed two latent factors, aligned with expected verbal/visual memory constructs. A female advantage was observed in verbal memory. Moderate age effects were observed on list learning/recall and small age effects on face-name learning/recall. All GLAMS subtests were correlated with NEPSY-II Sentence Repetition, supporting convergent validity with a measure of verbal working memory. The GLAMS is a psychometrically sound measure of learning and memory in Grenadian preschool children. Further adaptation and scale-up to global LMICs are recommended.

Assessing the expression of placental nutrient transporters following teratogenic valproic acid exposure in CD-1 mice.

Assessing the expression of placental nutrient transporters following teratogenic valproic acid exposure in CD-1 mice.

A Practical, Systematic Approach to Genetic Diagnosis in a Fetus or Neonate with Congenital Anomalies.

Congenital anomalies contribute significantly to perinatal, neonatal, and infant morbidity and mortality. The causes of these anomalies vary, ranging from teratogen exposure to genetic disorders. A high suspicion for a genetic condition is especially important because a genetic diagnosis carries a risk of recurrence in future pregnancies. Various methods are available for genetic testing, and each plays a role in establishing a genetic diagnosis. This review summarizes a practical, systematic approach to a fetus or neonate with congenital anomalies.

Population-based prevalence of congenital defects in a routine sentinel site-based surveillance system in the Western Cape, South Africa.

Lack of data on the burden and scope of congenital disorders (CDs) in South Africa undermines resource allocation and limits the ability to detect signals from potentially teratogenic pregnancy exposures. We used routine electronic data in the Western Cape Pregnancy Exposure Registry (PER) to determine the overall and individual prevalence of CD identified on neonatal surface examination at birth in the Western Cape, South Africa, 2016-2022. CD was confirmed by record review. The contribution of late (≤24 months) and antenatal diagnoses was assessed. We compared demographic and obstetric characteristics between women with/without pregnancies affected by CD. Women with a viable pregnancy (>22 weeks gestation; birth weight ≥ 500 g) (n = 32,494) were included. Of 1106 potential CD identified, 56.1% were confirmed on folder review. When internal and minor CD were excluded the prevalence of major CD identified on surface examination at birth was 7.2/1000 births. When missed/late diagnoses on examination (16.8%) and ultrasound (6.8%) were included, the prevalence was 9.2/1000 births: 8.9/1000 livebirths and 21.5/1000 stillbirths. The PER did not detect 21.5% of major CD visible at birth. Older maternal age and diabetes mellitus were associated with an increased prevalence of CD. Women living with/without HIV (or the timing of antiretroviral therapy, before/after conception), hypertension or obesity did not significantly affect prevalence of CD. A surveillance system based on routine data successfully determined the prevalence of major CD identified on surface examination at birth at rates slightly higher than in equivalent studies. Overall rates, modeled at ~2%, are likely underestimated. Strengthening routine neonatal examination and clinical record-keeping could improve CD ascertainment.

Applications of Zebrafish Embryo Models to Predict Developmental Toxicity for Agrochemical Product Development.

The development of safe crop protection products is a complex process that traditionally relies on intensive animal use for hazard identification. Methods that capture toxicity in early stages of agrochemical discovery programs enable a more efficient and sustainable product development pipeline. Here, we explored whether the zebrafish model can be leveraged to identify mammalian-relevant toxicity. We used transgenic zebrafish to assess developmental toxicity following exposures to known mammalian teratogens and captured larval morphological malformations, including bone and vascular perturbations. We further applied toxicogenomics to identify common biomarker signatures of teratogen exposure. The results show that the larval malformation assay predicted teratogenicity with 82.35% accuracy, 87.50% specificity, and 77.78% sensitivity. Similar and slightly lower accuracies were obtained with the vascular and bone assays, respectively. A set of 20 biomarkers were identified that efficiently segregated teratogenic chemicals from nonteratogens. In conclusion, zebrafish are valuable, robust, and cost-effective models for toxicity testing in the early stages of product development.

Discovery of DNA methylation signature in the peripheral blood of individuals with history of antenatal exposure to valproic acid

Discovery of DNA methylation signature in the peripheral blood of individuals with history of antenatal exposure to valproic acid

#2289 Pregnancy outcomes in patients with congenital abnormality of the urinary tract: experience of a tertiary Portuguese center

Abstract Background and Aims Congenital abnormalities of the urinary tract (CAKUT) represent a broad range of disorders that occur due to abnormal kidney development. Maternal, obstetric, and perinatal outcome in pregnant woman with CAKUT have not been extensively evaluated, although small series report an increased incidence of urinary tract infections (UTI) and obstructive uropathy. Method Retrospective analysis of maternal, obstetric, and perinatal outcomes in pregnant patients with CAKUT (including genetic cystic kidney disease) that were surveilled in our tertiary center by a nephro-obstetric team between 2011 and June 2023. Information was obtained from medical records. Results We evaluated 47 gestations in 41 patients, with mean age of 31 ± 5 years [17-40], 89% were Caucasian, 11% black; 40% were nulliparous, 36% had hypertension (HT) and 42% a previous history of UTI. Regarding CAKUT specificity, 17/41 patients had genetic cystic diseases, 10/41 ureteropelvic junction obstruction (UPJ), 4/41 duplicate collecting system, 5/41 vesicourethral reflux, 2/41 ectopic kidney, 3/41 renal hypoplasia. Genetic testing was done before, during or after pregnancy in 2/4/4 patients, respectively. Teratogenic therapy exposure occurred in 25% of gestations. Most patients were CKD stage 1 (33/41), with 2/4/1/1 with patients in CKD stage 2/3/4/5, respectively. Mean baseline SCr was 0.99 ± 0.8 mg/dL [0.4-4.6] and mean proteinuria was 194 ± 357 mg/g [22-1500]. Renal function (RF) deterioration occurred in 9/47 (19%) women due to pre-eclampsia (PE), pregnancy hyperfiltration (PH) and hydronephrosis in 3/3/3 patients, respectively. Urologic intervention was needed in 2 patients due to hydronephrosis, and one of the patients required transient dialysis. All patients fully recovered RF except for the 1 CKD stage 3 patients that had partial RF recovery. De novo and worsening proteinuria occurred in 7/47 gestations due to PE (3/7) and PH (4/7). De novo or aggravation of HTN occurred in 25% gestations, UTI in 19% and PE in 6% gestations. Regarding fetal outcomes, mean duration of gestation was 38 ± 2 weeks [32-41] and mean birth weight 2910 ± 634 g [1360-4600]. There was 1 miscarriage and 1 medical termination of pregnancy at 17 weeks (neural tube defect). Cesarean was performed in (8/47, 17%) gestations and 10/47 (17%) newborns were admitted to the neonatal care unit (NICU) mainly due to prematurity, sepsis and feeding intolerance. Conclusion Our cohort of CAKUT patients was very heterogenous and only 19.5% had CKD stage 2-5. Still, we found a significant incidence of maternal, obstetric, and perinatal complications, namely HT UTI, PE, and the need for NICU. UPJ obstruction can evolve with RF deterioration and the need for intervention during pregnancy. This study underlines the importance of the management of these patients by a multidisciplinary team.

Fertility and pregnancy complications in female orthopaedic surgeons.

While the number of female medical graduates continues to increase, only a few pursue an orthopaedic career. This is related to challenges regarding pregnancy and the peripartum period during orthopaedic training. To evaluate fertility, pregnancy-related complications and attitudes towards female orthopaedic surgeons in Israel. An electronic anonymous 34-question electronic web-based survey was sent to all Israeli female orthopaedic surgeons. Participation was voluntary. Questions were formulated to determine demographics, obstetrics medical history, teratogenic exposure, medical leave and breastfeeding parameters along with attitude towards pregnancy. Twenty-six orthopaedic surgeons complied with the survey, 68% of all registered female orthopaedic surgeons. Participants age was 39.5 (±8.8). The average number of children for a female orthopaedic surgeon was 2.2 (±1.4), with an average of 1.3 (±1.1) deliveries during residency. The average age for a first child was 31.1 (±3.7) years. Four surgeons required fertility treatments and six had abortions. Thirty-eight per cent experienced pregnancy complications. Most surgeons were exposed to radiation and bone cement during pregnancy. The average duration of maternity leave was 19.4 (±9.9) weeks and return to work was associated with cessation of breastfeeding. Seventy-six per cent of surgeons felt that pregnancy had negatively influenced their training, and 12% reported negative attitudes from colleagues and supervisors. Orthopaedic surgeons in Israel experience a delay in childbirth and higher rates of pregnancy complications. Most feel that their training is harmed by pregnancy. Programme directors should design a personalized support programme for female surgeons during pregnancy and the peripartum period.

The use of parent-completed questionnaires to investigate developmental outcomes in large populations of children exposed to antiseizure medications in pregnancy.

This study was undertaken to assess the utility of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and the Vineland Adaptive Behavior Scales-2nd Edition (VABS-II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large-population signal generation initiatives. Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development-3rd Edition (BSID-III), the VABS-II, and the ASQ-3 (n = 223). The sensitivity and specificity of the ASQ-3 and VABS-II to identify developmental delay at 24 months were examined, using the BSID-III to define cases. The ASQ-3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ-3 and BSID-III at 24 months, the ASQ-3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut-points resulted in improved properties and may be preferred in certain contexts. The VABS-II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID-III referral data (sensitivity = 100.0%, specificity = 96.6%). Both the ASQ-3 and VABS-II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at-risk groups. These findings identify the ASQ-3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS-II has excellent psychometric properties, it is more labor-intensive for both the research team and participants and is available in fewer languages than the ASQ-3.

Reduced fetal cerebral blood flow predicts perinatal mortality in a mouse model of prenatal alcohol and cannabinoid exposure

BackgroundChildren exposed prenatally to alcohol or cannabinoids individually can exhibit growth deficits and increased risk for adverse birth outcomes. However, these drugs are often co-consumed and their combined effects on early brain development are virtually unknown. The blood vessels of the fetal brain emerge and mature during the neurogenic period to support nutritional needs of the rapidly growing brain, and teratogenic exposure during this gestational window may therefore impair fetal cerebrovascular development.Study DesignTo determine whether prenatal polysubstance exposure confers additional risk for impaired fetal-directed blood flow, we performed high resolution in vivo ultrasound imaging in C57Bl/6J pregnant mice. After pregnancy confirmation, dams were randomly assigned to one of four groups: drug-free control, alcohol-exposed, cannabinoid-exposed or alcohol-and-cannabinoid-exposed. Drug exposure occurred daily between Gestational Days 12–15, equivalent to the transition between the first and second trimesters in humans. Dams first received an intraperitoneal injection of either cannabinoid agonist CP-55,940 (750 µg/kg) or volume-equivalent vehicle. Then, dams were placed in vapor chambers for 30 min of inhalation of either ethanol or room air. Dams underwent ultrasound imaging on three days of pregnancy: Gestational Day 11 (pre-exposure), Gestational Day 13.5 (peri-exposure) and Gestational Day 16 (post-exposure).ResultsAll drug exposures decreased fetal cranial blood flow 24-hours after the final exposure episode, though combined alcohol and cannabinoid co-exposure reduced internal carotid artery blood flow relative to all other exposures. Umbilical artery metrics were not affected by drug exposure, indicating a specific vulnerability of fetal cranial circulation. Cannabinoid exposure significantly reduced cerebroplacental ratios, mirroring prior findings in cannabis-exposed human fetuses. Post-exposure cerebroplacental ratios significantly predicted subsequent perinatal mortality (p = 0.019, area under the curve, 0.772; sensitivity, 81%; specificity, 85.70%) and retroactively diagnosed prior drug exposure (p = 0.005; AUC, 0.861; sensitivity, 86.40%; specificity, 66.7%).ConclusionsFetal cerebrovasculature is significantly impaired by exposure to alcohol or cannabinoids, and co-exposure confers additional risk for adverse birth outcomes. Considering the rising potency and global availability of cannabis products, there is an imperative for research to explore translational models of prenatal drug exposure, including polysubstance models, to inform appropriate strategies for treatment and care in pregnancies affected by drug exposure.

Prenatal Care Initiation and Exposure to Teratogenic Medications

With new legal abortion restrictions, timing of prenatal care initiation is critical to allow for discussion of reproductive options among pregnancies exposed to teratogenic medications. To investigate the prevalence of prenatal exposure to teratogenic medications and prenatal care initiation across gestational weeks. This descriptive, population-based cross-sectional study used health encounter data from a national sample of individuals with employer-sponsored health insurance. A validated algorithm identified pregnancies among persons identifying as female that ended with a live or nonlive outcome between January 2017 and December 2019. Data were analyzed from December 2022 to December 2023. Prenatal exposure to any of 137 teratogenic medications, measured via pharmacy and medical claims. Measurement of prenatal care initiation was adapted from the Children's Health Care Quality Measures. Prevalence of prenatal exposure to teratogens and prenatal care initiation by gestational week. Timing of prenatal teratogenic exposure was compared with timing of prenatal care initiation and legal abortion cutoffs. Among 639 994 pregnancies, 472 472 (73.8%; 95% CI, 73.7%-73.9%) had a live delivery (mean [SD] age, 30.9 [5.4] years) and 167 522 (26.2%; 95% CI, 26.1%-26.3%) had a nonlive outcome (mean [SD] age, 31.6 [6.4] years). Of pregnancies with live deliveries, 5.8% (95% CI, 5.7%-5.8%) were exposed to teratogenic medications compared with 3.1% (95% CI, 3.0%-3.2%) with nonlive outcomes. Median time to prenatal care was 56 days (IQR, 44-70 days). By 6 weeks' gestation, 8186 pregnancies had been exposed to teratogenic medications (25.2% [95% CI, 24.7%-25.7%] of pregnancies exposed at any time during gestation; 1.3% [95% CI, 1.3%-1.3%] of all pregnancies); in 6877 (84.0%; 95% CI, 83.2%-84.8%), prenatal care was initiated after 6 weeks or not at all. By 15 weeks, teratogenic exposures had occurred for 48.9% (95% CI, 48.4%-49.5%) of all teratogen-exposed pregnancies (2.5% [2.4-2.5] of all pregnancies); prenatal care initiation occurred after 15 weeks for 1810 (16.8%; 95% CI, 16.1%-17.5%) with live deliveries and 2975 (58.3%; 95% CI, 56.9%-59.6%) with nonlive outcomes. Teratogenic medications most used within the first 15 gestational weeks among live deliveries included antiinfectives (eg, fluconazole), anticonvulsants (eg, valproate), antihypertensives (eg, lisinopril), and immunomodulators (eg, mycophenolate). For nonlive deliveries, most antihypertensives were replaced by vitamin A derivatives. In this cross-sectional study, most exposures to teratogenic medications occurred in early pregnancy and before prenatal care initiation, precluding prenatal risk-benefit assessments. Prenatal care commonly occurred after strict legal abortion cutoffs, prohibiting consideration of pregnancy termination if concerns about teratogenic effects arose.

Updated EUROCAT guidelines for classification of cases with congenital anomalies.

Precise and correct classification of congenital anomalies is important in epidemiological studies, not only to classify according to etiology but also to group similar congenital anomalies together, to create homogeneous subgroups for surveillance and research. This paper presents the updated EUROCAT (European surveillance of congenital anomalies) subgroups of congenital anomalies and the updated multiple congenital anomaly (MCA) algorithm and provides the underlying arguments for the revisions. The EUROCAT methodology is described. In addition, we show how we validated the revised EUROCAT subgroups and MCA algorithm, which are both based on the International Classification of Diseases (ICD10/ICD9) codes. The updated EUROCAT subgroups and the updated MCA algorithm are described in detail and the updated version is compared to the previous versions. The EUROCAT subgroups and MCA algorithm provide a standardized and clear methodology for congenital anomaly research and epidemiological surveillance of congenital anomalies in order to facilitate the identification of teratogenic exposures and to assess the impact of primary prevention and prenatal screening policies. The EUROCAT subgroups and MCA algorithm are made freely available for other researchers via the EUROCAT Database Management Software.

Contraceptive use in women with mental illness in Soweto, South Africa.

The psychosocial and medical implications of unplanned pregnancy in women with mental illness (MI) are vast. International guidelines make clear recommendations about family planning for women with MI, particularly those exposed to known human teratogens; however, there is limited research related to contraceptive usage among women with MI. The aim of this study was to investigate the prevalence of consistent contraceptive use and family planning education (FPE) among a population of women of childbearing age with MI. This quantitative cross-sectional study was conducted at Chris Hani Baragwanath psychiatric unit in Soweto, South Africa. A convenience sample comprising 190 eligible women of childbearing age with MI was employed for the study. The women were invited to participate by means of a structured questionnaire which was administered by the researcher. Clinical information was obtained from the patients' medical records. Consistent contraceptive usage occurred in 44.7% of participants. Family planning education was low (26.8%). Relationship status was associated with using contraception consistently (p = 0.0229). Teratogen exposure was not associated with either contraceptive use or FPE. Family planning education was not associated with contraceptive use. Women with MI may have increased risk for unplanned pregnancy if they are not in a relationship because of perceived lack of need for contraception. Family planning education must be prioritised in women with MI, especially among women prescribed teratogenic medication, highlighting the risks associated with unplanned pregnancy.