Search Results (552)

Background/Objectives: Thyroid dysfunction during pregnancy is associated with a range of adverse perinatal outcomes. This study aims to evaluate the effect of maternal thyroid autoimmunity on selected gestational and perinatal outcomes of the newborn in a region with adequate iodine intake. Methods: This retrospective study included 74 full-term singleton pregnancies from women living in the coastal region of Romania. Participants were divided into two groups: group 1—women with chronic autoimmune thyroiditis and euthyroidism; group 2—women without thyroid disorders, serving as the control group. Maternal variables assessed included serum thyroid hormone levels and antithyroid autoantibodies. For newborns, parameters such as birth weight, neonatal TSH levels, and the incidence of gestational and perinatal events were evaluated. Results: The incidence of chronic autoimmune thyroiditis in the study population was 36.4%. Maternal thyroid autoimmunity was associated with an increased incidence of low birth weight, observed in 11% of the autoimmune group compared with 2.1% in the control group (p = 0.099). The incidence of preterm birth was significantly higher in the autoimmune group (18.5% vs. 4.2% in controls, p = 0.043), corresponding to a 4.3-fold increase in relative risk. The most frequent perinatal complication observed in pregnant women with thyroid autoimmunity was spontaneous abortion (11.1%). The median urinary iodine concentrations were within the adequate range in both study groups. Conclusions: Thyroid autoimmunity during pregnancy presents significant clinical challenges, even in areas with adequate iodine intake. Maternal autoimmune thyroiditis constitutes an established risk factor for impaired fetal development and adverse perinatal outcomes. Early assessment of thyroid function prior to conception or during the first trimester is recommended for both diagnostic and preventive purposes. Full article

Objectives: The aim of our study was to assess the efficacy and safety of two different labor induction methods in patients after fetal demise beyond 28 weeks, with an unfavorable cervix: misoprostol—prostaglandin E1 analog (PGE1) and dinoprostone—prostaglandin E2 analog (PGE2). Methods: This retrospective single-center cohort study included all labor cases after fetal demise (intrauterine fetal death or termination of pregnancy with feticide) from 28 to 40 weeks of gestation, where labor was induced by either PGE1 or PGE2. The primary outcome was the induction-to-delivery time interval. Secondary outcomes included the proportion of patients who delivered within 24 h, the failed induction rate, the length of labor, pain during induction, the adverse outcome rate, and the post-labor hospital stay. Results: The induction-to-delivery time interval was shorter in the PGE1 group (p = 0.048). There was no statistically significant difference in the proportion of patients who delivered within 24 h (p = 0.651) and failed inductions (p = 0.18) between groups. The duration of labor was longer in the PGE2 group (p = 0.01). Oxytocin augmentation was more common in the PGE2 group (p < 0.001). Pain during induction was greater in women in the PGE1 group (p < 0.001). There were no statistically significant differences in adverse effects between groups. There was no significant difference in induction to delivery interval between the two methods when comparing lower and higher gestational ages (28 to 34 weeks, p = 0.18; 35 to 40 weeks, p = 0.343). Conclusions: Our findings support the use of a PGE1 regimen for third-trimester labor induction after fetal demise, when no contraindications exist. This approach appears to improve the efficiency of induction and may enhance overall patient care by reducing intervention needs. Full article

Τhe intrauterine environment has a strong connection with the growing fetus and possible effects that can continue up to adulthood. Currently, stress is conceptualized as a modern teratogen. The overwhelming majority of studies indicate that maternal stress during pregnancy may have effects on pregnancy outcomes and fetal development, with long-lasting consequences on child and adult vulnerability to disease. Glucocorticoids are essential for regulating fetal development, growth, and metabolism. The two isoforms of 11beta-hydroxysteroid dehydrogenase enzyme (11β-HSD) mediate and regulate glucocorticoid actions and biological activity. It has not yet been fully elucidated whether maternal stress during pregnancy affects 11β-HSD isoenzyme activity and expression and results in possible adverse effects on fetal development, metabolism, and pregnancy outcomes. This review examines a possible pathophysiological mechanism by which maternal stress during pregnancy affects placental 11β-HSD isoenzyme activity, thereby causing adverse effects on the physiological status of pregnancy, fetal development, and metabolism. Furthermore, the main outcome of the review is the following: chronic and acute maternal stress during pregnancy affects the activity and the expression of placental 11β-HSD isoenzymes and has possible subsequent unfavorable results on preeclampsia, preterm birth, and fetuses with intrauterine growth restriction (IUGR) or small for gestational age (SGA) fetuses. Full article

Prenatal ozone (O₃) exposure may trigger systemic inflammation and oxidative stress. These effects could contribute to adverse pregnancy outcomes. We conducted a prospective cohort study involving 235 pregnant women in Ningxia, China. Maternal O₃ exposure during pregnancy and prior to conception was assessed using high-resolution spatiotemporal models. Multivariable logistic and linear regression analyses were employed to evaluate the associations between O₃ exposure and adverse pregnancy outcomes. Mediation and interaction models were further applied to examine the potential modifying roles of gestational diabetes mellitus (GDM) and inflammatory biomarkers. In multivariable analyses adjusted for maternal and environmental covariates, higher prenatal O₃ exposure was significantly associated with an increased risk of preterm birth (PTB) (OR = 1.24, 95% CI: 1.05~1.45, p = 0.010) and low birth weight (LBW) (OR = 1.29, 95% CI: 1.09~1.54, p = 0.004). Similarly, elevated maternal SAA and CRP levels were positively associated with these adverse pregnancy outcomes (p < 0.05). Notably, higher TNF-α levels were inversely associated with the risks of PTB (OR = 0.15, 95% CI: 0.03~0.85, p = 0.032) and LBW (OR = 0.05, 95% CI: 0.01~0.39, p = 0.005). IL-17A levels were inversely associated with neonatal length-for-age Z scores (β = −0.28, 95% CI: −0.55~−0.01, p = 0.043). Our findings suggest that prenatal O₃ exposure is associated with increased risks of PTB and LBW. Alterations in systemic inflammatory markers and metabolic dysfunction during pregnancy were related to adverse pregnancy outcomes and fetal growth deficits, but they did not mediate these associations, with O₃ remaining an independent predictor after adjustment. Full article

Chikungunya virus (CHIKV) infection during pregnancy represents an increasing public health concern, especially in endemic and epidemic regions. The main concern is vertical transmission, particularly during the peripartum period, which can lead to severe neonatal outcomes such as encephalopathy, hematologic abnormalities, and long-term neurodevelopmental impairment. This review synthesizes current knowledge on pathophysiology, clinical manifestations, diagnosis, maternal and neonatal outcomes, and management of CHIKV infection in pregnancy. Diagnosis relies on clinical evaluation supported by laboratory confirmation, RT-PCR in the acute phase and IgM serology thereafter. Treatment is supportive, using acetaminophen as first-line therapy and corticosteroids for selected refractory cases. No antivirals or vaccines are approved for use in pregnancy as of 2025. Prevention is centered on vector control, personal protection, and epidemiological surveillance. Delivery planning and neonatal monitoring are essential when infection occurs close to term due to the high risk of peripartum transmission. Despite growing recognition of CHIKV’s maternal–fetal impact, significant gaps remain regarding long-term outcomes and optimal management strategies. Strengthening prenatal care, neonatal preparedness, and surveillance systems is crucial to mitigate adverse outcomes and inform future clinical and public health policies. Full article

Background: Proper nutrition supports maternal and fetal health. Gaps in nutritional knowledge (NK) and nutritional literacy (NL) can affect maternal and fetal health. NK refers to knowing facts and processes about nutrition, while NL is a broader component that includes competencies and skills needed to obtain, understand, and apply nutrition information to make dietary decisions. NL and NK limitations may contribute to adverse maternal and neonatal outcomes. This scoping review aims to understand the relationship between NK, NL, and pregnancy outcomes, offering insights into areas for future nutrition-based interventions. Methods: Seven databases were searched for studies assessing NK and NL among pregnant women. A total of 5080 articles were identified, with 4249 retained after removing duplicates. Following title and abstract screening, 18 articles underwent full-text review, and 11 met the inclusion criteria. Data were extracted, analyzed, and categorized into nine key themes. Results: All eleven studies employed survey-based methods; ten focused on NK and one on NL. Overall, NK was generally low. The evidence for an association between NK or NL and pregnancy outcomes was limited. Education, income, occupation, and family influence were identified as key factors influencing the NK and NL of pregnant women. Education and income levels were identified as having the most significant impact on NK overall. Only one study accessed the relationship between NK and adverse birth and neonatal outcomes, and this only included HDP and preterm labor. Also, only one out of the eleven studies was conducted in the US. Conclusions: In this review, we found that NK and NL among pregnant women was generally low, with limited evidence linking it to pregnancy outcomes; education and income emerged as the most influential factors of NK and NL. Future studies in high-income countries are recommended to assess the association between NL and adverse maternal outcomes, especially GDM. Full article

Background/Objectives: Histological chorioamnionitis (HCAM) is a risk factor of chronic lung disease (CLD) in preterm neonates. Funisitis, an indicator of fetal inflammatory response, has been linked to adverse neonatal outcomes, but its impact on respiratory outcomes in extremely preterm neonates remains uncertain. In this study, we investigated whether HCAM with funisitis is associated with poorer respiratory outcomes when compared with HCAM alone in preterm (gestational age 22–36 weeks) neonates. Methods: This was a retrospective cohort study. We divided very low-birth weight (VLBW) preterm neonates with placenta histopathology examinations into three groups—normal, isolated HCAM, and HCAM with funisitis. Perinatal characteristics, radiographic findings, morbidities, and respiratory outcomes were compared. Results: Among 244 VLBW neonates, 25 (10.2%) had HCAM with funisitis, 88 (36.1%) had isolated HCAM, and the remaining 131 were in the normal group. Neonates with HCAM and funisitis had a significantly lower gestational age (26.44 ± 2.1 weeks) but a higher incidence of clinical chorioamnionitis (40.0%) than those with isolated HCAM (12.5%) or normal placentas (6.9%). Moreover, the incidence of cystic–interstitial lung changes before 2 weeks of postnatal age was higher in the HCAM with funisitis group (56.5%) than in the isolated HCAM group (25.0%), and the normal group (4.4%). CLD occurred in 66.7%, 37.7%, and 1.3% of these groups, respectively, and the need for home oxygen at follow-up was 26.1%, 13.7%, and 6.4%. Both isolated HCAM and HCAM with funisitis protected against severe respiratory distress syndrome. However, extremely preterm birth and funisitis had a more adverse impact on CLD development than HCAM alone (adjusted odds ratio 15.259 vs. 3.841). Conclusions: Funisitis independently predicts poor respiratory outcomes in extremely preterm infants. The long-term clinical impacts of funisitis in preterm infants should be further investigated. Full article

Background: Medication safety in pregnancy, puerperium, and perinatal periods is underexplored because these populations are excluded from clinical trials. EudraVigilance offers post-marketing evidence, but disproportionality analyses focus on isolated drug event pairs and may miss syndromic patterns. We applied a network- and cluster-based framework to EudraVigilance reports on antiviral use in pregnancy to improve surveillance and identify meaningful constellations. Methods: We retrieved all individual case safety reports (ICSRs) from January 2015 to June 2025, including pregnancy, puerperium, or perinatal terms, focusing on suspect antivirals. After parsing terms, disproportionality metrics were computed as a benchmark. A bipartite drug–event network was built and projected to event–event co-occurrence networks; Louvain community detection identified clusters. Clusters were characterized by size, drug mix, seriousness, overlap with disproportionality signals, and stratification across periods. Results: The dataset comprised 106,924 ICSRs and 232,067 unique pairs. Disproportionality yielded 6142 signals, mainly involving antiretrovirals (ritonavir, lamivudine, zidovudine, emtricitabine/tenofovir). Network analysis revealed clusters grouping maternal and fetal/neonatal outcomes (e.g., fetal death, low birth weight), and transplacental transfer, highlighting structures not visible in pairwise analyses. Several clusters combined high-frequency exposures with clinically relevant outcomes, suggesting early-warning potential. Conclusions: Combining disproportionality with network- and cluster-based pharmacovigilance adds value for monitoring pregnancy medication safety. Beyond individual signals, this approach reveals meaningful clusters and “bridge” reactions connecting adverse-event domains, offering a richer framework for perinatal surveillance. Despite spontaneous-reporting limits, findings generate hypotheses for mechanistic and pharmacoepidemiologic follow-up and support network methods as complements to traditional pharmacovigilance. Full article

Objective: To determine whether a third-trimester drop in insulin requirements in pregnant people with pre-existing diabetes is associated with a subsequent occurrence of adverse pregnancy outcomes. Research Design and Methods: We conducted a retrospective cohort study of patients with type 1 and 2 diabetes who were followed at a tertiary referral center in Toronto, Canada. We collected data on insulin dosing in the third trimester (after 28 weeks of pregnancy) and compared outcomes in those with and without a third-trimester drop of 15% or more in their total insulin requirements. Our primary outcome was a composite of stillbirth, spontaneous preterm birth or preterm premature rupture of membranes, and iatrogenic preterm birth or cesarean birth for fetal wellbeing concerns, occurring following the drop in insulin requirements. We conducted regression analyses controlling for early pregnancy glycosylated hemoglobin, body mass index, and diabetes-related microvascular disease, and presented results as odds ratios (OR) with 95% confidence intervals (95%CI). Results: We included 350 pregnant people—146 with type 1 and 204 with type 2 diabetes. Of these, 54 (15.4%) had a third-trimester drop of 15% or more in their total insulin requirements. There was no difference in the primary outcome between groups (OR 0.97; 95% CI 0.41–2.10). Conclusions: Based on this single-center study, limited by sample size and analytic constraints, in people with pre-existing diabetes, a third-trimester drop of ≥15% in total insulin requirements was not associated with subsequent occurrence of adverse pregnancy outcomes. Larger prospective studies looking at associations between a drop in insulin requirements and subsequent occurrence of adverse pregnancy outcomes are necessary to inform meta-analyses and clinical decision making. Full article

Toxoplasma gondii (T. gondii) infection during pregnancy can cause severe placental damage and fetal impairment. Although triggering the receptor expressed on myeloid cells 2 (Trem2) confers protection against T. gondii infection, the precise molecular mechanisms underlying this immunoregulatory role remain incompletely understood. Using a mouse model, this study identifies a novel Trem2-MICAL1-P-ERK axis in macrophages that protects against T. gondii-induced adverse pregnancy outcomes (APO). RNA-seq of Trem2-overexpressing macrophages revealed significant upregulation of 1857 genes, with MICAL1 among the most markedly altered, highlighting its potential role in Trem2-mediated signaling. Mechanistically, correlation analysis, molecular docking, fluorescence co-localization, and immunoprecipitation assays demonstrate that Trem2 directly interacts with MICAL1, which modulates downstream phosphorylated ERK (P-ERK) signaling. In a T. gondii-infected murine pregnancy model, genetic ablation of Trem2 exacerbated pathogen-induced suppression of MICAL1 and P-ERK, whereas macrophage-specific overexpression of Trem2-DAP12 restored this signaling axis. Conversely, MICAL1 overexpression rescued P-ERK activation but failed to regulate Trem2 expression. Further studies in bone marrow-derived macrophages (BMDMs) revealed that Trem2 deficiency potentiated the inhibitory effects of soluble T. gondii antigens (TgAg) on MICAL1 and P-ERK. These findings elucidate how T. gondii disrupts placental immunity through targeted suppression of Trem2-mediated signaling and establish the Trem2-MICAL1-P-ERK cascade as a core regulatory pathway in immune homeostasis during pregnancy. Full article

The medical condition of pregnancy-associated breast cancer (PABC) requires oncologists to determine the best way to protect both the mother and the fetus during cancer treatment. The safety profile of taxanes, including paclitaxel and docetaxel, in the second and third trimesters of pregnancy remains unclear despite well-established anthracycline-based regimens (e.g., doxorubicin). High-risk breast cancer subtypes such as triple negative breast cancer (TNBC) and human epidermal growth factor receptor (HER2)-positive disease require taxane chemotherapy as standard treatment in nonpregnant patients. Objective: This paper aims to gather available data about the safety, timing and fetal outcomes related to taxane chemotherapy during PABC, focusing on pharmacological and clinical guidance. Methods: A targeted literature review of PubMed and Scopus databases was performed to identify case series, cohort studies, and clinical guidelines addressing taxane use during pregnancy. This was not conducted as a formal systematic review or meta-analysis, but as a comprehensive narrative synthesis of available data. Results: The pharmacological properties of paclitaxel and docetaxel limit their placental transfer. Paclitaxel has not been associated with increased congenital anomalies; however, the long-term developmental data remain limited. Similarly, docetaxel administration shows no increase in major malformations. The most common approach used in PABC is to administer anthracyclines first and taxanes after 16–18 weeks’ gestation. The adverse effects experienced by pregnant patients match those experienced by nonpregnant patients. Conclusions: Taxanes can be used with caution after the first trimester in patients with PABC, especially in high-risk cases following anthracycline treatment. The absence of randomized trials combined with limited developmental data highlight the need for more standardized treatment approaches, aligning with current guideline recommendations. Full article

Oropouche virus (OROV), an emerging arbovirus of the Peribunyaviridae family, is responsible for acute febrile illness and, in some cases, neurological or hemorrhagic complications. Although traditionally confined to tropical areas of Central and South America, the 2024–2025 epidemic has signaled a major shift in its geographic and clinical profile, with sustained transmission in the Caribbean, over 15,000 confirmed cases, and the first imported infections reported in Europe and the United States. New clinical observations include fatalities in previously healthy adults, suspected vertical transmission with adverse fetal outcomes, and potential sexual transmission. Despite entomological data indicating low competence of European mosquito species and the absence of the main vector Culicoides paraensis, the increasing frequency of imported cases underscores the need for continued vigilance. Diagnostic limitations and clinical overlap with other arboviruses further complicate early detection. This review summarizes current knowledge on OROV’s epidemiology, transmission dynamics, and clinical features, and highlights the urgent need for integrated surveillance, diagnostic readiness, and coordinated research efforts. Emphasis is placed on Europe’s preparedness strategies, with Italy’s Jubilee 2025 offering a real-world case study for managing arboviral threats during mass gatherings. Full article

Background: Slow-transit constipation (STC) lacks durable and safe prokinetics. Deglycosylated-azithromycin (Deg-AZM), a novel small-molecule transgelin agonist that restores colonic motility in STC, has been approved for clinical trials in 2024. Objectives: This study aimed to assess the genetic toxicity and embryo–fetal development (EFD) toxicity of Deg-AZM through a series of standardized non-clinical safety studies. Methods: We conducted Ames, in vivo micronucleus, and chromosomal aberration tests to evaluate genotoxicity. Acute and 28-day repeated-dose oral toxicity studies were performed in Sprague-Dawley rats. EFD toxicity was assessed in pregnant rats administered Deg-AZM from gestation day (GD) 6 to 15. Toxicokinetic analyses were integrated into repeated-dose and EFD studies. Results: Deg-AZM demonstrated no mutagenic potential in the bacterial reverse-mutation assay at concentrations up to 2500 µg/plate (with metabolic activation) or 150 µg/plate (without metabolic activation). No clastogenic effects were observed in micronucleus or chromosomal aberration assays. The median lethal dose (LD₅₀) exceeded 1600 mg/kg in acute oral toxicity. In the 28-day study, no adverse effects were observed at doses up to 600 mg/kg, though mild hematological and hepatic changes were noted at high doses, all of which were reversible. In the EFD study, Deg-AZM did not induce maternal toxicity, teratogenicity, or adverse fetal outcomes at doses up to 600 mg/kg. Conclusions: Deg-AZM demonstrates a favorable safety profile with no evidence of genetic toxicity or developmental harm at pharmacologically relevant doses, supporting its further development as a therapeutic agent for STC. Full article

Background/Objectives: Cardiovascular risk (CVR) during pregnancy is an increasingly relevant topic due to its clinical significance and impact on maternal and fetal health. Pregnancy involves substantial physiological changes that may result in adverse outcomes such as gestational hypertension, gestational diabetes, obesity, and preeclampsia. These complications not only increase morbidity and mortality during pregnancy and the early postpartum period but also predispose women to long-term cardiovascular disease (CVD). Therefore, accurate assessment of CVR during pregnancy is essential for identifying risk factors and implementing preventive and therapeutic strategies tailored to the unique physiological context of gestation. To examine CVR during pregnancy and its long-term consequences, addressing etiological, diagnostic, and therapeutic aspects to provide an integrative perspective on the relationship between cardiovascular alterations and pregnancy. Methods: A scoping review was conducted in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Literature searches were performed in PubMed, Embase, and Scopus databases using terms related to pregnancy, cardiovascular diseases, and risk factors. The review covered studies published from 2019 to November 2024. A total of 205 articles were initially identified, of which 20 met the inclusion and exclusion criteria and were selected for analysis. Results: Pregnancy is considered a natural “cardiovascular stress test” that can unmask or trigger latent CVR factors. Complications such as preeclampsia, gestational diabetes, and intrauterine growth restriction are associated with a higher risk of developing CVD later in life. Genetic factors, such as telomere length, and specific biomarkers have emerged as promising tools for CVR assessment during pregnancy. Personalized management strategies—including regular monitoring and lifestyle modifications—have shown effectiveness in reducing both immediate CVR and the subsequent development of CVD, particularly in high-risk pregnancies. Conclusions: Pregnancy represents a unique window of opportunity for the early identification and management of CVR factors. These risk factors and obstetric complications have significant long-term implications, notably increasing the likelihood of future cardiovascular disease. Preventive and therapeutic interventions initiated during pregnancy are, therefore, crucial for improving maternal and neonatal outcomes and for reducing long-term cardiovascular morbidity. Full article

Objective: This study aimed to assess whether oocyte donation in triplet pregnancies is associated with increased risk of placental abnormalities and pregnancy complications compared to triplet pregnancies conceived through assisted reproductive technology (ART) without oocyte donation. Methods: This single-center, retrospective, case–control study analyzed triplet pregnancies conceived via ART. The case group included pregnancies resulting from oocyte donation, while the control group comprised triplet pregnancies conceived by ART without oocyte donation. Maternal, obstetric, fetal, and neonatal outcomes were assessed. Gross and histopathological placental findings were evaluated using standardized criteria. Univariate and multivariate statistical analyses were performed. Results: A total of 77 triplet pregnancies (231 fetuses) were included: 29 in the oocyte donation group (87 fetuses) and 48 in the non-oocyte donation group (144 fetuses). Multivariate analysis revealed significantly higher rates of pregnancy-induced hypertension (p = 0.03), preeclampsia (p = 0.03), fetal growth restriction (p = 0.04), and fetal death (p = 0.01) in the oocyte donation group. Placental evaluation showed a higher frequency of infarcts (p = 0.04) and chronic inflammatory lesions—chronic villitis (p = 0.02) and chronic deciduitis (p = 0.03)—as well as signs of fetal vascular malperfusion, including avascular villi (p = 0.02) and stromal–vascular karyorrhexis (p = 0.01). Intervillous fibrin deposition was also more common in this group (p = 0.02). Conclusions: Oocyte donation in triplet pregnancies is associated with increased rates of placental abnormalities and adverse maternal and fetal outcomes when compared with ART without oocyte donation. Placental examination may provide valuable insights into the mechanisms involved. Further research is warranted to clarify the underlying immunological and vascular pathways. Synopsis: In our cohort of 77 triplet pregnancies, those conceived via oocyte donation showed significantly higher rates of preeclampsia, fetal growth restriction, and fetal death. Placental examination revealed more chronic villitis, deciduitis, intervillous fibrin, avascular villi, and stromal–vascular karyorrhexis, suggesting immune and vascular dysfunction in oocyte donation pregnancies. Full article