Pregnancy Complications Research Articles

Cesarean Scar niche: Comparison of Transvaginal Ultrasound Findings and Uterine Tissue Samples after Hysterectomy

BackgroundThe cesarean scar (CS) niche, a consequence of incomplete wound healing, can lead to gynecological complications and affect future pregnancies. While internal niches have been well-studied, external and bidirectional niches are also important. ObjectivesWe aimed to conduct a comparative analysis of the prevalence and measurements of different types of niches. Study DesignThis cross-sectional study examined 200 patients with prior cesarean delivery (CD) undergoing hysterectomy due to abnormal uterine bleeding. It evaluated internal, external, and bidirectional niche prevalence, measurements (height, residual myometrial thickness, and adjacent myometrial thickness), and classification in hysterectomy specimens compared to pre-hysterectomy TVS reports. The secondary outcome was to determine niche presence in uterine tissue samples based on the number of previous CDs. ResultsThe mean age of the study participants was 48.19 years, with 30% having undergone only one CD. Notably, 83.5% had niches detected via sonography, while 91% had niches identified in uterine tissue samples post-hysterectomy (p-value =0.008). Internal niches were common, with significant associations between niche presence and the number of previous CDs. 23.3% of patients with one CD had internal niches. Additionally, external niches were detected in 4% of hysterectomy samples but not observed in ultrasound reports. Key parameters such as RMT and AMT differed notably between ultrasound and tissue samples, highlighting discrepancies in niche detection methods. RMT ranged from 2.8-24 mm (7.68 ± 3.09 mm) in ultrasound reports versus 0-25 mm (4.28 ± 2.71 mm) in tissue samples (p < 0.001). AMT ranged from 6-29 mm (17.08 ± 4.53 mm) in ultrasound reports versus 7.5-30 mm (16 ± 5.03 mm) in tissue samples (p < 0.001). This study underscores the importance of accurate niche assessment in patients with prior CD. ConclusionsWe performed a comparative analysis of niche prevalence and measurements in gross specimens and TVS reports. The results highlight the importance of considering external and bidirectional niches, in addition to internal niches. These niches can reduce residual myometrial thickness and increase future pregnancy complications. Furthermore, we demonstrated that niche formation can occur after a single CD.

Use of continuous glucose monitoring and hybrid closed-loop therapy in pregnancy.

Continuous glucose monitoring (CGM) has led to a paradigm shift in the management of pregnant women with type 1 diabetes (T1D), with improved glycaemic control, less hypoglycaemia and fewer pregnancy complications. Data on CGM use in pregnant women with type 2 diabetes (T2D) are limited. A large randomized controlled trial (RCT) on CGM use in people with T2D in pregnancy is ongoing. Small studies on CGM use in women with gestational diabetes (GDM) have suggested improved glycaemic control and better qualification when insulin is needed. However, none of these studies was powered to evaluate pregnancy outcomes. Several large RCTs are ongoing in women with GDM. In addition to CGM, other technologies, such as advanced hybrid closed-loop (AHCL) systems have further improved glycaemic management in people with T1D. AHCL therapy adapts insulin delivery via a predictive algorithm integrated with CGM and an insulin pump. A large RCT with the AHCL CamAPS® FX demonstrated a 10% increase in time in range compared to standard insulin therapy in a pregnant population with T1D. Recently, an RCT of an AHCL system not approved for use in pregnancy (780G MiniMed) has also demonstrated additional benefits of AHCL therapy compared to standard insulin therapy, with improved time in range overnight, less hypoglycaemia and improved treatment satisfaction. More evidence is needed on the impact of AHCL therapy on maternal and neonatal outcomes and on which glycaemic targets with CGM should be used in pregnant women with T2D and GDM. We review the current evidence on the use of CGM and AHCL therapy in pregnancy.

Utilizing Artificial Intelligence to Reconcile Indeterminate Lupus Anticoagulant Panel Results

Abstract Lupus anticoagulant (LA) is one laboratory criterion for diagnosing antiphospholipid antibody syndrome (APS), a condition associated with hypercoagulability, pregnancy complications, and death. LA diagnosis requires a complex panel, often performed at a specialized laboratory. Ruling out false positive or transient LAs requires ≥ two positive tests ≥ 12 weeks apart. Most LA tests are negative, with small subsets resulting positive or indeterminate. Indeterminates leave clinicians with limited understanding of appropriate clinical follow-up. Thus, the International Society on Thrombosis and Hemostasis discourages weak resulting nomenclature such as “indeterminate.” Our study used artificial intelligence to predict LA indeterminate results as positive or negative, identifying patients requiring further testing. This IRB approved study reviewed nearly 4000 LA tests performed from 2019-2023. Parameters included CBC, thromboelastography, renal/hepatic function assays, coagulation tests, antiphospholipid antibodies and LA tests. LA test components included screening tests (APTT, Dilute Russel Viper Venom Test (DRVVT) screen), mixing studies (1:1 APTT mix, DRVVT mix), phospholipid-dependent confirmation (DRVVT, hexagonal phase, platelet neutralization), and factor VIII. A positive LA test fulfilled 4 criteria: at least one positive screening test, mixing study and phospholipid-dependent assay and factor VIII inhibitor exclusion. An LA panel meeting 2-3 criteria resulted indeterminate. Studies meeting &amp;lt;2 criteria were negative. This analysis was performed using Machine Intelligence Learning Optimizer (MILO) platform which displays the performance of multiple models. MILO was trained with two classifications: positive and negative cases. Data was split into training (100 training positives; 100 negatives) and testing (primary and secondary validation) sets (100 positives; 1388 negatives). LA panels affected by drug interactions (9.4%) or containing incomplete datasets (21%) were excluded. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) determined model efficacy. 2903 negative (84%), 318 positive (9.1%), and 246 indeterminate (7.1%) LA results were included from 3467 patients. Only 84 of the 246 indeterminate patients (34%) were retested. Of these, 28 remained indeterminate, 43 became negative and 13 resulted positive. The best performing MILO models were the K-nearest neighbor (KNN) and logistic regression. The ability of these models to determine which indeterminate cases would become positive or negative was evaluated. KNN displayed the highest specificity (0.88) and PPV (0.57). All models had a high NPV and specificity due to substantive exposure to negative cases for the training and testing. Exclusion of some parameters did not improve the performance of the models. However, even the best model (various KNN models) had low sensitivity and PPV due to a small pool of positive training/testing cases and a much smaller group of indeterminate LA with subsequent positive results. Creating models accurately predicting indeterminate cases that may become positive enables appropriate clinical follow-up. Thus, improving model accuracy will require a larger sample size of positive indeterminates with follow-up.

Compliance with 24 h Movement Behavior Guidelines for Pregnant Women in Saudi Arabia: The Role of Trimester and Maternal Characteristics.

Complying with 24 h movement behavior guidelines for pregnant women may prevent pregnancy complications. This single time point, cross-sectional investigation assessed compliance with the 24 h movement behavior guidelines in pregnant women in Saudi Arabia and examined the role of trimester and maternal characteristics. Pregnant women (n = 935; age = 30 ± 5.6 years; first trimester = 24.1%, second trimester = 33.9%, third trimester = 42.0%) self-reported their characteristics (nationality, region, degree, occupation, smoking status, health status, having children, previous birth). The short-version International Physical Activity Questionnaire, Sedentary Behavior Questionnaire, and Pittsburgh Sleep Quality Index Questionnaire measured moderate physical activity (MPA), sedentary behavior (SB), and sleep duration, respectively. Compliance with the 24 h movement behavior guidelines was reported using frequencies and percentages. Prevalence ratios compared the prevalence of compliance by trimester and maternal characteristics. Approximately half of the participants did not comply with MPA or sleep duration guidelines (n = 524, [56.0%] and n = 424, [45.5%], respectively). In contrast, about two-thirds of participants (n = 648, [69.3%]) adhered to the SB guideline. Only 154 (16.5%) participants complied with all 3 24 h movement behavior guidelines. Pregnant women in their second trimester, living in Al-Ahsa Governorate, and currently smoking with a bachelor's degree were the most likely to comply with the guidelines. These findings underscore the need for tailored efforts to promote healthy 24 h movement behavior guidelines for pregnant women in Saudi Arabia, especially early in pregnancy, while accounting for important maternal characteristics.

The Role of Xanthine Oxidase in Pregnancy Complications: A Systematic Review.

Xanthine oxidoreductase (XOR) is an enzyme involved in the oxidation of hypoxanthine and xanthine to uric acid. XOR has two isoforms: xanthine dehydrogenase and xanthine oxidase (XO). XO plays a major role in oxidative stress, causing the formation of reactive oxygen species. In the present study, we aimed to summarize the evidence on the association between XO and pregnancy complications. The PRISMA checklist guided the reporting of the data. We conducted systematic searches in the PubMed and Web of Science databases to identify all human studies investigating XO in pregnancy diseases up to June 2024. A total of 195 references have been identified and 14 studies were included. Most studies focused on women with PE and GD. Overall, all the included studies found a statistically significant increase in maternal, placental, and/or fetal XO levels, activity, or tissue expression in women with pregnancy complications, compared to those with uncomplicated pregnancies. Although promising, the quality and dimension of the included studies do not allow for a definitive answer to the question of whether XO may play a crucial role in pregnancy complications. Future studies are warranted to confirm if XO could represent a prognostic and therapeutic marker in pregnancy complications and their impact on long-term maternal and offspring cardiovascular health.

High-risk pregnancy and risk of breastfeeding failure

BackgroundThere is growing evidence that supports the role of breastfeeding in reducing the burden of non-communicable diseases (NCDs). There are considerable gaps in breastfeeding outcomes in mothers with chronic diseases due to a lack of knowledge and support in the postpartum period. Mothers who have NCDs and pregnancy complications are at risk of breastfeeding failure.AimTo compare breastfeeding outcomes in mothers with NCDs with healthy mothers and determine the underlying challenges that lead to poor outcomes.MethodsA prospective cohort study was conducted among 150 women (50 with high-risk pregnancies (HRP) and 100 with normal pregnancies (NP)). They were recruited from those attending the immunization and outpatient clinics at Sohag General Hospital. Mothers were recruited at 34 weeks gestation and were followed up at 2 weeks, 6 weeks, and 6 months after delivery. A pretested and validated questionnaire was used to collect detailed epidemiological, personal, health-related status, medications, hospitalizations, reproductive history, current delivery, and previous breastfeeding experiences. On follow-up they were assessed for breastfeeding practices, their health and health and growth of their children, and social support.ResultsDelivery by cesarean section and postpartum bleeding were commoner among HRP patients. Initiation of breastfeeding in the 1st hour of delivery was significantly lower among women with HRP than those with normal pregnancies (48.0% versus 71.0%, p = 0.006). The most common reason for not initiating breastfeeding among the NP group was insufficient milk (34.5%), while in the HRP group, it was the mother’s illness (80.8%). Skin-to-skin contact with the baby after birth was significantly less practiced in the HRP than in the NP group (38.0% vs 64.0% at p = 0.003). Herbs (such as cumin, caraway, cinnamon, aniseed, and chamomile) were the most common pre-lacteal feeds offered (63.0% in NP vs 42.0% in HRP). Artificial milk was more used in HRP than NP (24.0% vs 4.0%). Breast engorgement was 3 times more common in the HRP compared to the NP group (61.5% vs19.6%). Stopping breastfeeding due to breast problems was 2.5 times higher in the HRP than in the NP group (38.5% vs. 15.2%, p = 0.003). Nipple fissures were twice as common among the NP than among the HRP group ((73.0%) vs. (38.5%), p = 0.026). Exclusive breastfeeding during the period of follow-up was lower in the HRP than in the NP group (40.0% vs 61.0%, p < 0.05) and formula feeding was twice as common in the HRP as in the NP group (34.0% vs. 18.0%, p = 0.015). Child illness was significantly higher among women with HRP than those with NP (66.0% vs 48.0%, p = 0.037).ConclusionsWomen with HRP are at a high risk of poor breastfeeding outcomes with increased lactation problems and formula feeding rates. Encouraging women especially those with HRP to achieve optimal breastfeeding practices is a simple intervention that can be included in daily practice and may have a positive impact on mothers’ health.

Phosphodiesterase Inhibitors in Fetal Growth Restriction: Do Not Forget to Consider Fetal Sex and Subcellular Compartmentation.

Fetal growth restriction (FGR) is a common complication of pregnancy, associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiometabolic diseases later in life. There is currently no effective approach to prevent or treat FGR, despite numerous animal and human studies assessing substances likely to improve fetal growth. Phosphodiesterase (PDE) inhibitors appeared as promising drugs to improve FGR management. However, to date, studies have led to somewhat disappointing or controversial results. In this Opinion article, we would like to draw attention to the need to consider the biological sex and the relative reactivity of human umbilical vein and arteries when developing therapeutic interventions to improve human umbilical circulation using PDE inhibitors. Indeed, we suspect that fetal sex, vessel type and the presence of FGR may influence subcellular compartmentation, which could jeopardize beneficial effects of PDE inhibitors.

A national study on maternal vomiting during pregnancy in Iran: prevalence, determinants, adverse birth outcomes, and the trend

BackgroundNausea and vomiting during pregnancy (NVP) is one of the most common complication of pregnancy. The present study was aimed to determine the association between vomiting during pregnancy and adverse birth outcomes.MethodsA cross-sectional study was conducted on 3649 pregnant women across 11 provinces of Iran. Cluster sampling method was used to select samples and data collection was done using family record and face-to-face interviews. Data were analyzed by logistic regression, using STATA14.2 software.ResultsThe prevalence of vomiting during pregnancy was 9.7% (95% CI: 8.8, 10.7), with an increasing trend by birth cohort. After adjusting for other confounders, the prevalence of vomiting revealed a decreasing trend by body mass index (OR = 0.63, 95%CI: 0.53, 0.78, P-trend < 0.001). In addition, long inter-pregnancy interval (IPI) significantly increased the odds of NVP (ORIPI of 1−3 year=2.42, ORIPI of >3 year=1.63). Multivariate analyses showed that the odds of stillbirth (AOR = 1.61, 95% CI: 1.17, 2.19) and the odds of infant mortality (AOR = 1.78, 95% CI: 1.29, 2.45) were significantly increased in women with daily vomiting during pregnancy. The odds of vomiting during pregnancy was significantly shown to reduce the odds of abortion by 45%.ConclusionThe prevalence of NVP was shown to have an increasing trend in Iran. This complication is associated with many adverse health outcomes during pregnancy and negatively affect maternal and fetal health. Given the importance of pregnancy period, nutrition education and increase the awareness of pregnant women towards NVP, especially pre-pregnancy training is suggested.

Thrombotic complications in pregnancy: a case-based review of the evidence

Pregnancy is a prothrombotic state due to an estrogen-driven shift in the coagulation system, increased venous stasis, and external restriction of blood flow caused by the gravid uterus. Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in pregnancy. Preventing, recognizing, and treating thrombosis in pregnancy, as well as the postpartum period, often challenges decision making in the clinical setting. In early pregnancy, guidance with respects to thrombophilia testing and anticoagulation in increasing the likelihood of live birth among patients with recurrent miscarriages is evolving. This review explores emerging data that support clinical decision making in thrombosis care in women with common thrombotic complications in pregnancy. The first case outlines VTE diagnosis in pregnancy, initial anticoagulation management, management around delivery and postpartum, and subsequent long-term anticoagulation treatment. The second case examines testing for inherited and acquired thrombophilia in the setting of recurrent miscarriage and the management of obstetric antiphospholipid syndrome. Lastly, the third case reviews VTE risk assessment and prevention in pregnancy and the postpartum period, as well as duration and dose of postpartum thromboprophylaxis. Review of these common clinical scenarios surrounding thrombotic complications in pregnancy demonstrates recent advances in high-quality data, current gaps in knowledge, and variation in expert opinion. Ultimately, multidisciplinary discussion and teamwork remain key to optimal, safe care. Clinicians must prioritize collaborative, high-quality trials and prospective clinical management studies to better understand and define best practice in this population.

Hierarchical Classification of Factors Associated With Noninvasive Prenatal Testing Failures and Its Impact on Pregnancy Outcomes

Abstract Objective To conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to alleviate their anxiety. Methods In this study, 30,039 singleton pregnancies who underwent noninvasive prenatal testing in a single center from May 2019 to April 2022 were collected, and 811 samples with initial noninvasive prenatal testing failure were retrospectively analyzed. Grouping was based on the reasons for initial test failure; tracking the noninvasive prenatal testing results and prenatal diagnosis results (if any) of the “z-scores in the gray area” group and analyzing the possible influencing factors of the “low fetal fraction” group in the pre-experimental and experimental period by using one-way analysis of variance, Mann-Whitney U test, and χ2 test; and tracking the pregnancy outcomes of the test failures samples to analyze the risk of perinatal complications and adverse pregnancy outcomes of the different types of test failures. Results None of the samples' initial nonresults because of z-scores in the gray area were ultimately found to have chromosomal aneuploidy. However, pregnancy complications (P = 0.018) and a high likelihood of adverse pregnancy outcomes (P = 0.048) may still occur. Maternal gestational age (P &lt; 0.001), body mass index (P &lt; 0.001), library concentration (P &lt; 0.001), and fetal gender (P &lt; 0.001) were considered to be the associated factors for the initial low fetal fraction results. This may be associated with pregnancy complications (P &lt; 0.001) and a high likelihood of adverse pregnancy outcomes (P = 0.034). The body mass index (P = 0.015) and time between draws (P = 0.001) were associated with the second test’s success. The incidence of low fetal fraction samples was more frequent with blood collection tubes of the G type than with the K type (P &lt; 0.001). Conclusion Initial nonresults because of z-scores in the gray area did not imply an increased risk of aneuploidy, but vigilance is needed for an increased risk of pregnancy complications and adverse pregnancy outcomes. Because of the low fetal fraction, the initial absence of results may be related to the assay method, as well as the effect of blood collection tubes and the need to be alert to the risk of pregnancy complications and adverse pregnancy outcomes.

What are the experiences of pregnancy for women living with Inflammatory Bowel Disease?

BackgroundInflammatory Bowel Disease (IBD) is a long-term condition affecting the digestive tract and is an umbrella term for two main conditions: ulcerative colitis (UC) and Crohn's Disease (CD), which can cause diarrhoea, anaemia, weight loss, rectal bleeding and abdominal pain. Approximately 500,000 people live with IBD in the UK, with half being diagnosed before the age of 35 years (Ferguson, Mahsud-Dornan, and Patterson 2008). IBD increases the risk of pregnancy complications, with symptoms being unpredictable during pregnancy. MethodsA mixed methods study was undertaken exploring what shaped the experiences of pregnancy for women living with IBD, including an on-line survey and one-to-one interviews. Data from the interviews were analysed using Interpretative Phenomenological Analysis. FindingsExpectations, control and care emerged as key themes which shape the experiences of pregnancy. These included expectations about pregnancy and of those providing care during pregnancy, the positive and negative impact of experienced lack of control and the effects of primary care providers during pregnancy. ConclusionThis novel study enabled women living with IBD to share what shaped their experiences of pregnancy and recommendations about midwifery care to be made. Midwives need to be mindful of the additional risks for women and their babies, and ensure care involves multidisciplinary specialists.

Reproductive Experiences of Physicians in Medical and Surgical Subspecialties.

Objective: To evaluate the reproductive experiences of physicians across gender and specialty. Patients and Methods: Between November and December 2021, we surveyed nontrainee physicians of all genders at a single quaternary institution using a modified version of an existing survey instrument. Experiences with family planning, fertility, pregnancy, and parental leave were assessed. Results: There were 422 completed responses. Respondents reported a higher prevalence of infertility as compared to the general U.S. population (26% versus 19%), with no difference in infertility or obstetrical complications by specialty. Most respondents (75%) reported stigma regarding having children in medicine, and 71% reported delaying childbearing. These trends were strongest in the subanalysis of female respondents. Forty-five percent of respondents reported that their work increased the risk for subfertility, infertility, or pregnancy complications. Surgeons were significantly more likely to report physically demanding work conditions (75% versus 30%, p < 0.001), radiation exposure (39% versus 14%, p < 0.001), and bloodborne pathogen exposure (25% versus 12%, p = 0.03) as occupational reproductive hazards. Only 55% of respondents with a pregnancy history reported ever taking parental leave. Among those who took less than the full amount offered, 63% cited concerns about falling behind educationally or professionally as significantly influencing this decision. Conclusions: These results support previous trends showing delayed childbearing and increased infertility among physicians while shedding new light on stigma associated with childbearing and parental leave. A better understanding of the reproductive experiences of physicians is critical to recruiting and retaining a skilled workforce and fostering career and life satisfaction in this profession.

Transplacental SARS-CoV-2 protein ORF8 binds to complement C1q to trigger fetal inflammation.

Prenatal SARS-CoV-2 infection is associated with higher rates of pregnancy and birth complications, despite that vertical transmission rates are thought to be low. Here, multi-omics analyses of human placental tissues, cord tissues/plasma, and amniotic fluid from 23 COVID-19 mother-infant pairs revealed robust inflammatory responses in both maternal and fetal compartments. Pronounced expression of complement proteins (C1q, C3, C3b, C4, C5) and inflammatory cytokines (TNF, IL-1α, and IL-17A/E) was detected in the fetal compartment of COVID-19-affected pregnancies. While ~26% of fetal tissues were positive for SARS-CoV-2 RNA, more than 60% of fetal tissues contained SARS-CoV-2 ORF8 proteins, suggesting transplacental transfer of this viral accessory protein. ORF8-positive fetal compartments exhibited increased inflammation and complement activation compared to ORF8-negative COVID-19 pregnancies. In human placental trophoblasts in vitro, exogenous ORF8 exposure resulted in complement activation and inflammatory responses. Co-immunoprecipitation analysis demonstrated that ORF8 binds to C1q specifically by interacting with a 15-peptide region on ORF8 (C37-A51) and the globular domain of C1q subunit A. In conclusion, an ORF8-C1q-dependent complement activation pathway was identified in COVID-19-affected pregnancies, likely contributing to fetal inflammation independently of fetal virus exposure.

Dysregulated GLUT1 results in the pathogenesis of preeclampsia by impairing the function of trophoblast cells

Preeclampsia (PE) is a common placental-origin complication of pregnancy and a major cause of morbidity and mortality among pregnant women and fetuses. However, its pathogenesis has not been elucidated. Effective strategies for prevention, screening, and treatment are still lacking. Studies have indicated that dysfunction of placental trophoblast cells, such as impaired syncytialization, proliferation, and epithelial-mesenchymal transition processes, plays a crucial role in the development of PE. Glucose transporter 1 (GLUT1) is a key protein regulating glucose transport in placental tissues. However, the effect of GLUT1 on the function of trophoblast cells in PE is not well understood. In this study, we found that GLUT1 expression is reduced in PE placental tissues. GLUT1 promotes the syncytialization process by increasing the glucose uptake ability of BeWo cells. Additionally, GLUT1 promotes the proliferation, migration, and invasion capabilities of HTR-8/SVneo cells by regulating MAPK and PI3K/AKT signaling pathways. Overall, these findings provide a new insight into understanding the biological functions of GLUT1, clarifying the pathogenesis of PE, and identifying diagnostic and therapeutic targets for PE.

The Safety of Alcohol Pharmacotherapies in Pregnancy: A Scoping Review of Human and Animal Research.

Alcohol pharmacotherapies pose unknown teratogenic risks in pregnancy and are therefore recommended to be avoided. This limits treatment options for pregnant individuals with alcohol use disorders (AUD). The information on the safety of these medications during pregnancy is uncertain, prompting a scoping review. The objective of this review was to investigate available information on the safety of alcohol pharmacotherapies in pregnancy. Studies published between January 1990 and July 2023 were identified through searches in BIOSIS, Embase, PsycINFO and MEDLINE databases, using terms related to pregnancy and alcohol pharmacotherapies. The alcohol pharmacotherapies investigated were naltrexone, acamprosate, disulfiram, nalmefene, baclofen, gabapentin and topiramate. Studies were screened by two independent reviewers. Covidence software facilitated the management, screening and extraction of studies. A total of 105 studies were included in the review (naltrexone: 21, acamprosate: 4, disulfiram: 3, baclofen: 3, nalmefene: 0, topiramate: 55, gabapentin: 32) with some studies investigating multiple medications. Studies investigating naltrexone's safety in pregnancy focussed on opioid use disorders, with limited evidence regarding its safety in the context of AUD. Despite concerns about higher rates of some pregnancy complications, studies generally indicate naltrexone as a safer option compared with opioid agonists or alcohol during pregnancy. Acamprosate was not clearly associated with adverse effects of exposure in pregnancy, with two pre-clinical studies suggesting potential neuroprotective properties. Disulfiram has a high risk of congenital anomalies when used in pregnancy, believed to be due to its mechanism of action. Prenatal topiramate has also been associated with an increased risk of congenital anomalies, particularly oral clefts. There were mixed results concerning the safety of prenatal gabapentin and little to no literature investigating the safety of baclofen or nalmefene during pregnancy. There is insufficient research on the safety of alcohol pharmacotherapies in pregnancy. Despite this, given alcohol's teratogenic effects, naltrexone could be considered to help maintain abstinence in pregnant individuals with AUD, particularly when psychosocial treatments have failed.

Confined Placental Mosaicism Detected With Non-Invasive Prenatal Testing: Is There an Association Between Mosaic Ratio and Pregnancy Outcome?

Confined placental mosaicism (CPM) is associated with an increased risk for pregnancy complications, such as fetal growth restriction (FGR), preterm birth and hypertensive disorders. Pregnancies with possible CPM can be identified with non-invasive prenatal testing (NIPT). We performed a retrospective cohort study to investigate whether the mosaic ratio, as calculated with the Veriseq v2 used for NIPT, can predict adverse pregnancy outcomes in cases of CPM. A mosaic ratio for trisomies detected by NIPT and obstetric data such as fetal growth, structural fetal anomalies and birthweight were retrospectively studied in a cohort of patients with CPM diagnosed between February 2021 and October 2023. Structural and sex chromosomal aberrations were not included in this study. Of 122 CPM cases, 52 cases (42.6%) showed adverse perinatal outcomes, including FGR, low birthweight, hypertensive disorders, or preterm birth. A significantly higher mosaic ratio was found in the adverse outcome group compared to those with normal outcome, but a clear-cut threshold could not be set, except potentially for trisomy 16. There is an association between the mosaic ratio and adverse pregnancy outcomes in cases of CPM. However, without a clear-cut threshold, it cannot be used for the individual patient for differentiation between CPM with and without clinical consequences.

Effect of environmental air pollutants on placental function and pregnancy outcomes: a molecular insight.

Air pollution has become a major health concern, particularly for vulnerable populations such as the elderly, children, and pregnant women. Studies have reported a strong association between prenatal exposure to air pollutants and adverse pregnancy outcomes, including lower birth weight, reduced fetal growth, and an increased frequency of preterm births. This review summarizes the harmful effects of air pollutants, such as particulate matter, on pregnancy and outlines the mechanistic details associated with these adverse outcomes. Particulate pollutant matter may be able to cross the placenta barrier, and alterations in placental functions are central to the detrimental effects of these pollutants. In addition to associations with preeclampsia and gestational hypertension, air pollutants also induce oxidative stress, inflammation, and epigenetic alteration in the placenta. These pollutants can also affect placental homeostasis and endocrine function, contributing to pregnancy complications and possible transgenerational effects. Prenatal air pollution exposure has been linked to reduced cognitive and motor function in infants and newborns, increasing the predisposition to autism spectrum disorders and other neuropsychiatric disorders. This review also summarizes the use of various animal models to study the harmful effects of air pollution on pregnancy and postnatal outcomes. These findings provide valuable insight into the molecular events associated with the process and can aid in risk mitigation and adopting safety measures. Implementing effective environmental protocols and taking appropriate steps may reduce the global disease burden, particularly for developing nations with poor regulatory compliance and large populations of pregnant women.

Breastfeeding in the prevention of long-term consequences of neuropsychiatric pathology in offspring with gestational diabetes mellitus

This literature review summarizes modern concepts of gestational diabetes mellitus as an independent risk factor for the development of long-term neuropsychiatric diseases in offspring and the mechanisms of their programming in this complication of pregnancy in the absence of the protective role of maternal melatonin as a consequence of chronodestruction. The article presents literature data on the composition of breast milk and the participation of its endogenous melatonin, microRNAs, long non-coding RNAs, stem cells, and microbiome in reprogramming epigenetic disorders as a result of adverse effects in the antenatal period, which helps to reduce the likelihood of developing neuropsychiatric pathology later in life. It is emphasized that breastfeeding during the first six months of life and later, along with complementary foods under the age of two years and older, is exclusively a physiological and unsurpassed method of preventing long-term consequences of impaired brain development in offspring with gestational diabetes mellitus.

Effects of Dietary Quality on Vaginal Microbiome Composition Throughout Pregnancy in a Multi-Ethnic Cohort.

Background: Vaginal Lactobacillus predominance is associated with improved vaginal health and reduced pregnancy complications. Little is known about how dietary quality may improve vaginal microbial composition or about dietary interventions that may promote Lactobacillus abundance. To understand the host factors affecting vaginal microbiota during pregnancy in a multi-ethnic cohort in Hawai`i. We hypothesize that better diet quality improves vaginal microbial composition, as represented by Lactobacillus abundance and depletion of anaerobic organisms. Methods: We compared comprehensive diet quality, as measured by the Healthy Eating Index-2015 (HEI-2015), to taxonomic classifications of bacteria present within the vagina. Participants of the four predominant ethnic groups in Hawai'i (Japanese, Filipino, Non-Hispanic White and Native Hawaiian) completed Quantitative Food Frequency Questionnaires (QFFQs) and collected vaginal swabs during each trimester. 16s rRNA amplicon sequencing (V2-V9 regions) was performed on vaginal samples. HEI-2015 scores and macro- and micronutrient intake were compared with the predominant species present using the Mann-Whitney-U test, PERMANOVA, and the Pearson correlation coefficient. A mixed-effects logistics regression model was used to predict the depletion of Lactobacillus species while accounting for confounding demographic factors. Results: Matched, longitudinal data for 40 participants demonstrated three predominant Lactobacillus species: L. crispatus, L. iners, and L. gasseri, with another subset of samples with anaerobic abundance. (Primarily, Atopobium vaginae, Prevotella, and Gardnerella vaginalis.) Non-Hispanic White participants had lower amounts of Lactobacillus iners compared to other racial and ethnic groups. HEI scores correlated with the chao index and observed species number primarily in the first trimester (r = 0.25, p < 0.05). Greater carbohydrate intake was associated with a higher abundance of L. crispatus, while lower carbohydrate intake trended towards more L. iners (0.056) and anaerobic species. Conclusions: Increased carbohydrate consumption and improved diet quality may be associated with beneficial vaginal microbial composition in pregnancy.

Infertility treatment and offspring blood pressure-a systematic review and meta-analysis.

Studies have inconsistently observed that children conceived by IVF or ICSI have higher blood pressure compared to children not conceived by these ARTs. The aim was to perform a systematic review and meta-analysis of blood pressure measures of offspring conceived by ART and those conceived naturally. Resolving the suspicion of ART as a risk factor of higher blood pressure, and therefore of heart disease, has public health and clinical implications. A biomedical librarian searched the Embase, PubMed, and Web of Science databases. Searches were limited to records published in English since 1978. Grey literature was searched. Inclusion criteria were humans born via infertility treatment (vs no treatment) who underwent a blood pressure assessment. Exclusion criteria were non-human participants, non-quantitative studies, absence of a control group, and specialty populations (e.g. cancer patients only). Two reviewers independently screened each record's title and abstract and full text using Covidence, extracted data using Excel, and assessed bias using the National Heart, Lung, and Blood Institute's Quality Assessment Tool for cohort studies. Of 5082 records identified, 79 were included in the systematic review and 36 were included in the meta-analysis of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in ART and non-ART groups. Overall, 34 reports including 40 effect sizes from 25 unique cohorts, compared blood pressure between ART (N = 5229) and non-ART (N = 8509, reference) groups with no covariate adjustment. No standardized mean differences (SMD) in SBP (0.06 per SD of mmHg, 95% CI = -0.05, 0.18) or DBP (0.11, 95% CI = -0.04, 0.25) by treatment were found, but the heterogeneity was considerable (I2=76% for SBP and 87% for DBP). Adjusted analyses were presented in 12 reports, representing 28 effect sizes from 21 unique cohorts (N = 2242 treatment vs N = 37590 non-treatment). Studies adjusted for varied covariates including maternal (e.g. age, education, body mass index, smoking, pregnancy complications), child (e.g. sex, age, physical activity, BMI, height), and birth characteristics (e.g. birth weight and gestational age). Adjusted results similarly showed no SMD for SBP (-0.03, 95% CI = -0.13, 0.08) or DBP (0.02, 95% CI = -0.12, 0.16), though heterogeneity remained high (I2 = 64% and 86%). Funnel plots indicated a slight publication bias, but the trim and fill approach suggested no missing studies. Removal of five studies which adjusted for birth outcomes (potentially over-adjusting for mediators) made no material difference. Type of treatment (e.g. IVF vs ICSI), period effects by birth year (≤2000 vs >2000), offspring age group (<8, 8-14, 15+), or study location (e.g. Europe) did not modify the results. In conclusion, conception by ART was not associated with offspring blood pressure in a meta-analysis, although considerable heterogeneity was observed. Given the increasing number of children born using ART, perpetuating a difference in blood pressure would mean unnecessary risk screening for many children/adults on a population level. At a clinical level, couples considering these reproductive technologies have some reassurance that there is no evidence of strong vascular 'programming' due to the techniques used. PROSPERO No. CRD42022374232.