Potential Fetal Risks Research Articles

Characteristics, Physiopathology and Management of Dyslipidemias in Pregnancy: A Narrative Review.

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). During pregnancy, physiological changes elevate cholesterol and triglyceride levels to support fetal development, which can exacerbate pre-existing conditions and lead to complications such as pre-eclampsia, gestational diabetes, and increased ASCVD risk for both mother and child. Effective management strategies are necessary, especially for pregnant women with inherited forms of dyslipidemia (i.e., familial hypertriglyceridemia, hyperchylomicronemia), where personalized dietary adjustments are crucial for successful pregnancy outcomes. Pharmacological interventions and lipoprotein apheresis may be necessary for severe cases, though their use is often limited by factors such as cost, availability, and potential fetal risks. Despite the promise of advanced therapies, their widespread application remains constrained by limited studies and high costs. Thus, a personalized, multidisciplinary approach is essential for optimizing outcomes. This review provides a comprehensive overview of current strategies and evidence-based practices for managing dyslipidemia during pregnancy, emphasizing the balance of maternal and fetal health. Additionally, it discusses the physiological changes in lipid metabolism during pregnancy and their implications, particularly for women with inherited forms of dyslipidemia.

Collagens of placenta composition in obese puerperant women who gave birth to сhildren at St. Petersburg State Pediatric Medical University in 2018–2021

BACKGROUND: The relevance of the problem of obesity is associated with the high frequency and steady growth of this pathology in the population. The epigenetic influence of maternal obesity on the course of pregnancy and childbirth, as well as on the condition of the fetus and newborn, is currently being studied. This article analyzes changes in the composition of the connective tissue of the placenta against the background of obesity in pregnant and puerperas. AIM: The aim of this study is to identify the pathomorphological features of the placenta and the composition of placental collagens in women who were obese before pregnancy and at the time of delivery at the Perinatal Center of St. Petersburg State Medical University from 2018 to 2021 to assess potential fetal risks and to predict possible complications during pregnancy and in the postnatal period for the mother. MATERIALS AND METHODS: A histological examination of the placentas of obese women (18 patients) and the ones with a normal body mass index (18 patients) who gave birth to mature newborns at the Perinatal Center of St. Petersburg State Medical University from 2018 to 2021 was performed followed by immunohistochemical examination. Staining of placenta specimens was carried out in accordance with the standard immunohistochemical protocol, using primary antibodies to type I–IV collagen. RESULTS: Microscopic examination of chorionic villi revealed no significant differences in the presence of chronic inflammation and angiogenesis disorders between the groups. When studying collagen expression levels, the following differences have been found: in the group of pregnant obese patients, the optical luminescence density and distribution area for type I–III collagen in the placenta were significantly higher, while for type IV collagen they were significantly lower compared with the control group. CONCLUSIONS: The following features of the formation of connective tissue in the placenta in obese mothers have been revealed: an increase in type I–III collagen production and a decrease in type IV collagen production. The obtained findings indicate an earlier functional and morphological change in the placenta than those detected by standard histological methods.

Catheter ablation for focal atrial tachycardias during pregnancy: A systematic review

ObjectivePregnancy can trigger maternal tachycardias, and the onset of recurrent or incessant focal atrial tachycardia (AT) can lead to tachycardia-induced cardiomyopathy. Medical interventions are commonly employed, but they carry potential fetal and maternal risks. Catheter ablation (CA), particularly with non-fluoroscopic navigation systems, may be considered as an alternative. This systematic review aims to explore the feasibility and outcomes of CA for focal AT during pregnancy. MethodsA thorough literature search was conducted until September 30th, 2023, on PubMed, Embase, and Cochrane databases. Included articles described maternal focal ATs diagnosed through electrophysiological studies and treated with CA. Data derived from these studies were organized into tables and subsequently analyzed. ResultsOut of 278 papers reviewed, 15 articles involving 24 patients were retrieved. CA, utilizing radiofrequency energy achieved acute success in 95.8% of cases. Sixteen patients (66.7%) underwent complete fluoroless procedures, with two adverse events directly related to the procedure reported. Long-term follow-up revealed minimal AT recurrences, with a 0.06% arrhythmia burden in one case. ConclusionFocal ATs during pregnancy can be incessant and refractory to medical intervention, precipitating an acute decline in left ventricular ejection fraction. In this setting, CA emerges as an efficacious treatment modality, particularly in cases of tachycardia-induced cardiomyopathies. Whenever feasible, it is advisable to perform these procedures with minimal or no fluoroscopy guidance. Larger studies are needed to establish the safety and the efficacy of CA for focal ATs during pregnancy, as current research consists of case reports or small case series.

Pharmacotherapy of Chronic Neuropsychiatric Conditions During Pregnancy

Many pregnant persons will experience neuropsychiatric conditions during pregnancy, including migraine, attention deficit disorder, depression, and anxiety. Treatment of each of these conditions requires shared decision-making among the individual, family, and health care team. Although medications may include risk, the benefits often outweigh the potential fetal risks. In this article, we review pharmacologic treatment options for each of these conditions and appropriate use in pregnancy to maintain the stability of conditions and to optimize maternal and fetal outcomes.

Evaluation of a Microphysiological Human Placental Barrier Model for Studying Placental Drug Transfer

Understanding drug transport across the placental barrier is important for assessing the potential fetal drug toxicity and birth defect risks. Current in vivo and in vitro models have structural and functional limitations in evaluating placental drug transfer and toxicity. Microphysiological systems (MPSs) offer more accurate and relevant physiological models of human tissues and organs on a miniature scale for drug development and toxicology testing. MPSs for the placental barrier have been recently explored to study placental drug transfer. We utilized a multilayered hydrogel membrane-based microphysiological model composed of human placental epithelial and endothelial cells to replicate the key structure and function of the human placental barrier. A macroscale human placental barrier model was created using a transwell to compare the results with the microphysiological model. Placental barrier models were characterized by assessing monolayer formation, intercellular junctions, barrier permeability, and their structural integrity. Three small molecule drugs (glyburide, rifaximin, and caffeine) that are prescribed or taken during pregnancy were studied for their placental transfer. The results showed that all three drugs crossed the placental barrier, with transfer rates in the order: glyburide (molecular weight, MW = 494Da) < rifaximin (MW = 785.9Da) < caffeine (MW = 194.19Da). Using non-compartmental analysis, we estimated human pharmacokinetic characteristics based on in vitro data from both MPS and transwell models. While further research is needed, our findings suggest that MPS holds potential as an in vitro tool for studying placental drug transfer and predicting fetal exposure, offering insights into pharmacokinetics.

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

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

Multiple sclerosis in pregnancy. Treatment options and outcomes: a review

Background. Women are commonly diagnosed with multiple sclerosis during reproductive age. There is need for disease control management during pregnancy, taking into consideration potential maternal and fetal risks. This review article aims to summarize what is acknowledged so far regarding treatment options of multiple sclerosis and outcomes in pregnancy, providing up-to-date information. Methods. In order to write this review a comprehensive literature electronic search for journal articles and guidelines regarding multiple sclerosis during pregnancy was undertaken. Results and conclusion. Multiple sclerosis management in pregnancy is a challenging issue. The use of disease-modifying drugs has improved both the course of the disease and the attitude towards pregnancy in patients living with multiple sclerosis. Pregnancy appears to have a protective effect on disease activity, particularly during the third trimester.

ANAESTHETIC MANAGEMENT IN CAESAREAN SECTION IN A PARTURIENT WITH KYPHOSCOLIOSIS : A CASE REPORT

Alterations in maternal physiology and pathological changes in kyphoscoliosis results in anaesthetic complications for caesarean section with potential risk for both mother and fetus. Safe and skilled anaesthetic management to minimize risk to mother and fetus is required. We report a case of 25-year-old female, with G2P1L1, with 28 weeks of period of gestation, with history of previous caesarean section, with pre-eclampsia, with kyphoscoliosis in labour with contracted pelvis, managed by general anaesthesia for caesarean section.

Participation in a randomised controlled trial (RCT) of metformin in gestational diabetes mellitus (GDM): pregnant women's perceptions and experiences of the decision-making process.

Background: Research in pregnancy and childbirth is required to advance healthcare needs for this population. Fears around potential fetal risk and the history of drug scandals renders it an area of research that is somewhat neglected. Due to the growing medical complexities facing pregnant women, efforts have been made in recent times to recognise the ethical importance of including this population in clinical research.Although clinical trials are becoming more common in pregnancy, recruitment of this population remains difficult with a common assumption that pregnant women would be reluctant to participate in clinical trials. This study set out to explore pregnant women's perspectives and experiences of the decision-making process to participate in a randomised controlled trial of metformin in gestational diabetes mellitus (the EMERGE clinical trial). Methods: This study employed a qualitative descriptive design with thematic analysis. Data were collected by conducting individual semi-structured interviews (n=11) with participants (n=9) and decliners (n=2) of the EMERGE clinical trial. Results: The main findings reveal that a significant perception of personal benefit from participation was the biggest influence on women's decisions to participate. Concerns about the impact of gestational diabetes on their pregnancies, the option of a favourable intervention treatment, a low perception of risk associated with the trial and the opportunity to help medical research appeared to have significantly influenced their decision. Receiving detailed information, personal interactions with the study team, a perception of voluntariness in participation and accessibility of the trial positively impacted on women's decisions to participate. Conclusions: Personal contact during recruitment, presenting clear and thorough trial information, providing previous participant testimonials, and facilitating women to participate in clinical trials are all important strategies when trying to enhance recruitment in pregnancy trials. Further research on pregnant women declining participation in clinical trials is needed.

EDITORIAL COMMENT

This manuscript provides a modern summary of management of renal and bladder malignancies in pregnant women, including both the spectrum of disease observed and the surgical principles to be considered. The historical mentality of avoiding interventions to women during pregnancy has certainly evolved for many urologic and other conditions, and in the setting of malignancy, this manuscript emphasizes the safety and favorable maternal oncological survival rates associated with intervention. Guidelines and standard management principles should provide the foundation for treatment decisions, and as the authors discuss, the gestational age, mother's wishes and potential fetal risks are essential factors as well.

Non-Invasive Prenatal Fetal Blood Group Genotype and Its Application in the Management of Hemolytic Disease of Fetus and Newborn: Systematic Review and Meta-Analysis.

Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.

COMPARATIVE STUDY OF TREATMENT OF GESTATIONAL DIABETES MELLI-TUS CITED IN VARIOUS AYURVEDIC AND MODERN RESEARCH PAPERS PUB-LISHED IN LAST 5 YEARS

Gestational Diabetes Mellitus is a metabolic disorder during pregnancy. It is defined by WHO as carbohy-drate intolerance resulting in hyperglycemia of variable severity with onset or first recognition during preg-nancy. The entity usually present late in second and third trimester. The factors which constitute good health, i.e. balanced Dosha, Dhatu and Mala, optimally functioning Indriyas or sense organs, a happy con-tented soul and a balanced mind are the very factors that go towards a smooth pregnancy, labour and healthy progeny and this is what Ayurveda treatment focuses on. Pregnancy is a particular time for all women. This condition becomes even more delicate when there is diagnosis of GDM which makes neces-sary controls and therapies that will inevitably affect the women’s life. GDM can lead to potential risk for mother, fetus and child’s development. There is no direct reference of GDM in Ayurveda. But we get ref-erence of Garbhavriddhi excessive increase in size of abdomen and perspiration. Garbhavriddhi or mac-rosomia condition can be interpreted as complication of GDM. In current scenario GDM in pregnancy is one of the major complications during pregnancy. Overt maternal diabetes mellitus can adversely influence intrauterine development. Spontaneous abortions and major congenital anomalies may be induced in the first trimester. Excessive foetal growth, neonatal hypoglycemia, still birth may be induced during second and third trimester. Gestational Diabetes may lead to gangrene, damage of retina, kidneys. If diabetes is not properly controlled, then in the long run fat gets deposited on inner layer of arteries and the possibilities of occurrence of paralysis increase. Complications of diabetes include eye problems and blindness, heart dis-ease, stroke, neurological problems, amputation, and impotence It is needed to cure maternal diabetes as soon as it is diagnosed. Adopting pre-conceptional and thorough antenatal care through Ayurveda; this aims that a woman enters pregnancy in healthy state of body and mind. While describing Garbhadhan vidhi acharyas have advised certain body purifying measures (Sanshodhana karma) followed by special dietet-ics and mode of life for the couple. Ayurveda focuses on change in lifestyle of the Garbhini which helps in maternal health and fetal growth minimizing the complications related to pregnancy. Ayurveda efforts of having healthy baby commences with pre-conception care and management. Pre-conception counselling, Diet, Herbs, Yoga, Asanas are useful as a supportive therapy together with modern medication under su-pervision. The best way to improve your diet is by eating a variety of healthy foods. Various vegetables, pulses, spices, cereals, fruits, dry fruits are helpful in GDM patients. Daily 20 mins walk is also helpful. Ayurvedic herbs like Guduchi, Amalaki, Haritaki, Haridra, Bilva, Neem, Jamun are also useful in GDM. They are having antidiabetic, antioxidant properties. Tinospora Cordifolia are potential therapeutics that act as anti-diabetic drug in the prevention and treatment of GDM. Metformin is safe and effective drug in treatment of GDM. Combination of metformin, diet, Ayurvedic herbs, preconception counselling, Yoga, Pranayama and meditation can give best result in GDM.

Medicines for headache before and during pregnancy: a retrospective cohort study (ATENA study)

ObjectiveTo investigate headache treatment before and during pregnancy.BackgroundMost headaches in pregnancy are primary disorders. Headaches are likely to ameliorate during pregnancy, although they may also begin or worsen. Most headache medications should be avoided during pregnancy because of potential fetal risks. However, only scarce evidence on headache drug consumption during pregnancy is available.DesignATENA was a retrospective, self-administered questionnaire-based, cohort study on women in either pregnancy or who have just delivered and reporting headache before and/or during pregnancy.ResultsOut of 271 women in either pregnancy or who have just delivered, 100 (37%) reported headache before and/or during pregnancy and constituted our study sample. Before pregnancy, the attitude toward the use of symptomatic drugs was characterized by both a strong focus on their safety and the willingness to avoid possible dependence from them. Compared to the year before, pregnancy led to changes in behavior and therapeutic habits as shown by a higher proportion of patients looking for information about drugs (44/100 [44%] vs. 36/100 [36%]) and a lower proportion of those treating headache attacks (88/100 [88%] vs. 52/100 [52%]) and by a lower use of nonsteroidal anti-inflammatory drugs (68/100 [68%] vs. 5/100 [5%]) and a much higher use of paracetamol (33/100 [33%] vs. 95/100 [95%]).ConclusionsPregnancy changes how women self-treat their headache, and leads to search for information regarding drug safety, mostly due to the perception of fetal risk of drugs. Healthcare providers have to be ready to face particular needs of pregnant women with headache.

Pregnancy and cardiovascular disease.

Cardiovascular disease complicates 1-4% of pregnancies - with a higher prevalence when including hypertensive disorders - and is the leading cause of maternal death. In women with known cardiovascular pathology, such as congenital heart disease, timely counselling is possible and the outcome is fairly good. By contrast, maternal mortality is high in women with acquired heart disease that presents during pregnancy (such as acute coronary syndrome oraortic dissection). Worryingly, the prevalence of acquired cardiovascular disease during pregnancy is rising as older maternal age, obesity, diabetes mellitus and hypertension become more common in the pregnant population. Management of cardiovascular disease in pregnancy is challenging owing to the unique maternal physiology, characterized by profound changes to multiple organ systems. The presence of the fetus compounds the situation because both the cardiometabolic disease and its management might adversely affect the fetus. Equally, avoiding essential treatment because of potential fetal harm risks a poor outcome for both mother and child. In this Review, we examine how the physiological adaptations during pregnancy can provoke cardiometabolic complications or exacerbate existing cardiometabolic disease and, conversely, how cardiometabolic disease can compromise the adaptations to pregnancy andtheir intended purpose: the development and growth of the fetus.

Medication prescribing pattern and potential teratogenicity risk among pregnant women at Hidar 11 General Hospital, south Wollo, northeast Ethiopia

Drugs given to pregnant mothers for therapeutic purposes may cause serious structural and functional adverse effects in the developing child. However, the fact that drugs are needed to mitigate complications during pregnancy cannot be totally avoided. Hence, the current study is aimed to evaluate the pattern of medication prescribing practice during pregnancy at Hidar 11 General Hospital, Ethiopia. Institution based cross sectional study was conducted on 310 pregnant women whose medical charts were selected using systematic random sampling from antenatal care (ANC) attendants at Hidar 11 General Hospital. Data was collected through medical chart review by using data abstraction tool and analyzed by statistical package for social sciences (SPSS) Version 24 software. Among the study participants, 263 (84.8%) had a prescription at least for one drug during their pregnancy. Majority of the drugs prescribed for the pregnant women were vitamins and minerals (60.6%), antibacterial agents (30.6%) and central nervous system drugs (28.4%). A high proportion of drugs were prescribed from US Food and Drug Administration (US FDA) category C (57.7%) followed by category B (50.6%) and category A (22.9%). Only 6.8% of the prescribed drugs were with positive evidence of risk (US FDA category D) during all trimesters and no drugs were prescribed from proven fetal risk category (US FDA X category). Even though, drugs from category X were not prescribed, a significant number of pregnant women consumed drugs with potential fetal risk that should be addressed by informing the prescribers to stick to the treatment guidelines and seek safer options.&#x0D;

Chapter 26 - Pregnant women, prescription, and fetal risk

Since the historical scandal of thalidomide in the 1960s, practitioners and future mothers are fearful of drugs during pregnancy. In-uterine exposure to drugs can induce major malformation of the fetus or even intrauterine fetal death. Prescribing drugs to a pregnant woman requires particular attention, and it is necessary to consider both the maternal needs and the proven and potential fetal risks. In this chapter, we review the mechanisms for medication transfer from mother to fetus, fetal risk according to pregnancy timeline, and the main dangerous drugs during pregnancy. We also focus on three prescription debates, which are relevant for neurodevelopmental disorder, because they each point to a paradigmatic situation-diethylstilbestrol, which shows transgenerational adversary effects; valproate, which impacts neurodevelopment as a whole; and antidepressants for which the adverse impact on neurodevelopment is still controversial given the impact of depression itself. Finally, we consider the implications for practice and toxicologic research to promote risk prevention.

MRI in pregnancy: Indications and practical considerations.

There is a constantly evolving knowledgebase regarding the safety of MRI in pregnant patients, as well as the safety of gadolinium administration, given potential fetal risks. This review provides an overview of national and international recommendations for patient screening and safety by trimester, evaluates the most recent literature regarding administration of gadolinium in pregnant patients, and discusses technical requirements when imaging pregnant patients. A protocol for imaging pregnant patients is provided, and multiple common indications for MRI in pregnancy are discussed. Level of Evidence 5. Technical Efficacy Stage 5. J. Magn. Reson. Imaging 2019;49:621-631.

Hair dyes in pregnant women; is it safe?

Statins (3-hydroxy-3 methyl-glutaryl coenzyme-A reductase inhibitors) are the most commonly prescribed cholesterol-lowering medications due to their efficacy in reducing cardiovascular mortality and morbidities, tolerability, and safety profiles. Based on pathophysiologic similarities between cardiovascular disease and preeclampsia, a common and dangerous complication of pregnancy, there is an increasing interest in studying this class of medications during pregnancy to prevent and/or treat preeclampsia. Undergoing such a study, which entails the use of a pregnancy class X medication for an off-label indication in pregnancy, requires intensive multidisciplinary involvement of a group of experts in basic and clinical pharmacology, research methods, pregnancy physiology and maternal–fetal medicine, as well as U.S. Food and Drug Administration (FDA) regulatory guidelines and practice. Issues of potential fetal risk, altered maternal–fetal pharmacokinetics and pharmacodynamics, and regulatory challenges are real, and must be carefully considered in the process of research in this arena.

Diabetes and Pregnancy

Diabetes and Pregnancy

The serological diagnostic of toxoplasmosis in children and pregnant women using immune chemical technique by test-systems of various manufacturers

The toxoplasmosis is a disease representing a potential risk for fetus. This is the reason to detect antibodies to agent of the given infection in case of any suspicion to intrauterine infection. The analysis was applied to 65 samples of blood serum of newborns, children of the frst year of life and pregnant women. The IgG antibodies were detected in 21.5% and 26.2% of individuals examined by test-systems Euroimmun AG and Virion-Serion. The IgM antibodies were detected in 9.4% of individuals examined by test systems of both manufacturers. To make verifcation of the results of detection of antibodies to toxoplasmosis even more reliable avidity of specifc IgG antibodies is to be analyzed.