Search Results (1,302)

Substance use during pregnancy is an increasingly important yet under-recognized threat to maternal and child health. This narrative review synthesizes the current evidence available on the epidemiology, pathophysiology, clinical management, and policy landscape of prenatal exposure to alcohol, tobacco, opioids, benzodiazepines, cocaine, cannabis, methamphetamines, and other synthetic drugs. All major psychoactive substances readily cross the placenta and can remain detectable in breast milk, leading to a shared cascade of obstetric complications (hypertensive disorders, placental abruption, pre-term labor), fetal consequences (growth restriction, structural malformations), and neonatal morbidities such as neonatal abstinence syndrome and sudden infant death. Mechanistically, trans-placental diffusion, oxidative stress, inflammatory signaling, and placental vascular dysfunction converge to disrupt critical neuro- and cardiovascular developmental windows. Early identification hinges on the combined use of validated screening questionnaires (4 P’s Plus, CRAFFT, T-ACE, AUDIT-C, TWEAK) and matrix-specific biomarkers (PEth, EtG, FAEE, CDT), while effective treatment requires integrated obstetric, addiction, and mental health services. Medication for opioid use disorders, particularly buprenorphine, alone or with naloxone, confers superior neonatal outcomes compared to methadone and underscores the value of harm-reducing non-punitive care models. Public-health strategies, such as Mexico’s “first 1 000 days” framework, wrap-around clinics, and home-visiting programs, demonstrate the potential of multisectoral interventions, but are hampered by structural inequities and punitive legislation that deter care-seeking. Research gaps persist in polysubstance exposure, culturally tailored therapies, and long-term neurodevelopmental trajectories. Multigenerational, omics-enabled cohorts, and digital longitudinal-care platforms represent promising avenues for closing these gaps and informing truly preventive perinatal health policies. Full article

Preeclampsia (PE) is a hypertensive disorder impacting 5–7% of pregnancies globally. With no causative treatment available, diagnosed patients have limited therapeutic options, putting them at risk for pregnancy complications. The induction of oxidative stress by ROS—one of the major contributors in PE pathogenesis—causes downstream signaling and production of anti-angiogenic factors, such as sFLT1 and sEng. The anti-angiogenic factors may cause endothelial and trophoblast dysfunction, contributing to the development of hypertension, proteinuria, and in severe cases, eclampsia. To target placental oxidative stress, we developed and evaluated an organofluorine hydrazone antioxidant, HY-12, in vitro. Human trophoblast (HTR8/SVneo) cells were incubated with hydrogen peroxide to induce oxidative stress and act as a model of PE. The goal of the study was to assess the efficacy of HY-12 and its ability to reduce cell injury, mitochondrial stress, and anti-angiogenic response. In our human trophoblast-based assays, pre-treatment with HY-12 reduced mitochondrial-derived ROS production in cells exposed to hydrogen peroxide, proving its ability to alleviate the oxidative stress associated with the pathogenesis of PE. HY-12 reduced HIF1A expression and sFLT1 protein expression in H₂O₂-exposed HTR8 cells. Furthermore, HY-12 improved the activity of the mitochondrial electron chain enzyme cytochrome C oxidase (COX) in the hydrogen-peroxide-treated HTR8/SVneo cells, which is a promising attribute of the compound. In reducing placental trophoblast oxidative stress, HY-12 shows promise as a potential treatment of preeclampsia. In vivo studies are warranted to further determine the efficacy of this compound. Full article

Background: A short cervix in the second trimester significantly increases preterm birth risk, yet no reliable first-trimester prediction method exists. Current guidelines lack consensus on which women should undergo transvaginal ultrasound (TVUS) screening for cost-effective prevention. Therefore, it is vital to establish a highly accurate and economical method for use in the early stages of pregnancy to predict short cervix in mid-pregnancy. Methods: A total of 1480 pregnant women with singleton pregnancies and at least one risk factor for spontaneous preterm birth (<37 weeks) were recruited from January 2020 to December 2020 at the Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Cervical length was assessed at 20–24 weeks of gestation, with a short cervix defined as <25 mm. Feature selection employed tree models, regularization, and recursive feature elimination (RFE). Seven machine learning models (logistic regression, linear discriminant analysis, k-nearest neighbors, support vector machine, decision tree, random forest, XGBoost) were trained to predict mid-trimester short cervix. The XGBoost model—an ensemble method leveraging sequential decision trees—was analyzed using Shapley Additive Explanation (SHAP) values to assess feature importance, revealing consistent associations between clinical predictors and outcomes that align with known clinical patterns. Results: Among 1480 participants, 376 (25.4%) developed mid-trimester short cervix. The XGBoost-based prediction model demonstrated high predictive performance in the training set (Recall = 0.838, F1 score = 0.848), test set (Recall = 0.850, F1 score = 0.910), and an independent dataset collected in January 2025 (Recall = 0.708, F1 score = 0.791), with SHAP analysis revealing pre-pregnancy BMI as the strongest predictor, followed by second-trimester pregnancy loss history, peripheral blood leukocyte count (WBC), and positive vaginal microbiological culture results (≥10⁵ CFU/mL, measured between 11⁺⁰ and 13⁺⁶ weeks). Conclusions: The XGBoost model accurately predicts mid-trimester short cervix using first-trimester clinical data, providing a 6-week window for targeted interventions before the 20–24-week gestational assessment. This early prediction could help guide timely preventive measures, potentially reducing the risk of spontaneous preterm birth (sPTB). Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy, increasing the risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, obesity, and family history have demonstrated strong association with GDM, but no clear pathophysiology has been ascertained. Methods: An analysis was conducted on 38 women with and 296 without GDM, within a case/control study of pre-eclampsia. The genetic variants examined were selected from among a published polygenic risk score of 10 variants (PRS-10). Genetic models were evaluated for each variant by multivariate logistic regression methods adjusted for age, body mass index, and pre-eclampsia. Since the genotypes for three of the PRS-10 were not available, a risk score comprising the total risk alleles among seven of the variants (PRS-7) was evaluated among those with all genotypes available. Results: Multivariate logistic regression showed significant, independent, positive associations between body mass index (BMI) and age. The posited PRS-7 showed a trend (OR 1.56, 95% CI 0.92–2.56, p = 0.070), and sensitivity analysis comprising three variants (PRS-3) was significantly associated with GDM (OR 2.43, 95% CI 1.17–5.06, p = 0.017). In univariate analysis, rs1421085 was associated with GDM (OR 0.50, 95% CI 0.26–0.95, p = 0.034), but not after adjustment for covariates, and paradoxically not for the expected risk allele. None of the other six variants showed an individual association with GDM. The previously published meta-analysis of PRS-10 showed a degree of heterogeneity (p_Q= 0.03) among the three cohorts analyzed, suggesting that variant effects may differ according to the genetic background, which points to the importance of examining the generalizability of any posited polygenic risk scores. Conclusions: In conclusion, we provide additional support for and further refine the results of a previously published polygenic risk score for GDM in an ethically unrelated population. Full article

Background/Objectives: Heart disease affects 0.1% to 4% of pregnant women, with congenital heart defects being the leading cause in developed countries. While maternal mortality is generally low, pre-existing cardiac conditions substantially increase adverse outcome risks. This report describes the multidisciplinary management of a pregnant patient with a bicuspid aortic valve, severe aortic stenosis, and ascending aortic ectasia. Case Presentation: A 34-year-old pregnant woman, asymptomatic but at high risk (World Health Organization Class III) for hemodynamic decompensation, was closely monitored throughout gestation. At 36 weeks, intrauterine growth restriction was detected, prompting an elective cesarean delivery at 38 weeks. Postpartum, the patient developed pre-eclampsia, which was managed successfully. Imaging revealed progressive aortic dilation, leading to surgical aortic valve replacement and ascending aorta reduction plasty. Post-operatively, atrioventricular reentrant tachycardia from an unrecognized accessory pathway developed; medical therapy effectively controlled the arrhythmia after failed catheter ablation. One year later, both mother and child remained in good health. Discussion: This case illustrates the complexity of managing pregnancy in women with congenital heart disease and significant aortic pathology. The physiological changes of pregnancy can exacerbate underlying lesions, necessitating individualized risk assessment, vigilant monitoring, and timely intervention. Conclusions: A multidisciplinary approach involving cardiology, obstetrics, anesthesiology, and genetics is essential to optimize outcomes for pregnant women with significant heart disease. As advances in care allow more women with congenital heart defects to reach childbearing age, structured care pathways remain vital for ensuring safe pregnancies and long-term cardiovascular health. Full article

Background/Objectives: Fetal exposure to essential metals, such as iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn), is influenced by maternal nutrition and lifestyle during pregnancy, potentially impacting newborn health. This study aimed to quantify concentrations of these metals in meconium and evaluate their associations, together with newborn length and weight, in relation to maternal dietary and lifestyle factors. Methods: This cross-sectional study included 152 mother–infant pairs recruited from various regions of Split-Dalmatia County, Croatia. Meconium samples were collected within 24 h after birth and analyzed for Fe, Zn, Cu, and Mn concentrations. Maternal characteristics, dietary intake, supplement use, and lifestyle factors were collected via structured questionnaires and supplemented by hospital records. Associations among maternal factors, meconium metal concentrations, and newborn birth weight and length were assessed using non-parametric statistical methods. Results: Meconium concentrations of Fe, Zn, Cu, and Mn showed substantial interindividual variability, with a strong positive correlation between Fe and Cu. Higher maternal pre-pregnancy BMI was linked to lower meconium Fe, while BMI at delivery was associated with Zn. Dietary patterns influenced metal levels: higher fruit intake was linked to increased Cu, greater vegetable intake with lower Fe, and moderate tea consumption with higher Zn. No significant associations were found with maternal smoking, residence, or supplement use. Maternal meat consumption and higher pre-pregnancy BMI were both associated with higher newborn birth weight and length. Conclusions: Maternal BMI and specific dietary patterns during pregnancy significantly influence essential metal concentrations in newborn meconium and are associated with newborn size, highlighting the importance of balanced maternal nutrition and healthy metabolic status during pregnancy. Full article

Background/Objective: Pregnancy-related acute kidney injury (PRAKI) remains a serious complication, with high rates of maternal morbidity and mortality, particularly in developing countries where delayed diagnosis and treatment are common. This study aimed to determine the proportion, associated risk factors, and maternal outcomes among pregnant and postpartum women at high risk of developing AKI. Methods: This cross-sectional analytical study was conducted at Bugando Medical Centre in Mwanza, Tanzania, from May 2023 to February 2024, targeting high-risk obstetric patients. Results: Out of 4588 admissions, 420 patients were identified as being at risk of developing PRAKI. Among them, 101 (24.22%) were diagnosed with PRAKI, while 316 (75.78%) did not develop the condition. The leading associated risk factors were pre-eclampsia (40.59%) and postpartum hemorrhage (PPH) (40.24%), followed by sepsis (11.8%) and abortion-related complications (5.94%). Multivariate analysis revealed that living in rural areas and having a lower level of education were significantly associated with PRAKI. Patients from rural areas had an adjusted odds ratio (AOR) of 5.37 (p < 0.001), while those with informal or primary education had an AOR of 4.21 (p = 0.048). Conclusions: The study also found that maternal mortality was significantly higher among patients with PRAKI, particularly those affected by PPH. These findings highlight the urgent need for improved management of obstetric emergencies to reduce PRAKI incidence and improve maternal outcomes in high-risk populations. Full article

Purpose: In 2020, a lockdown due to COVID-19 was ordered by the German government, resulting in population-wide restrictions. In this retrospective study, we question the extent to which health policy restrictions have influenced medical diagnoses. Methods: The incidence rates of relevant pregnancy complications during all trimesters of pregnancy were evaluated for a 6-month pre-pandemic period (April–September 2019), in comparison to the same period during the lockdown in 2020. Mothers and newborns who presented at the University Hospital St. Hedwig, Regensburg, Germany, were included in the study. The incidence rates of preeclampsia and suspected FGR (fetal growth retardation), as relevant obstetric diseases, were further compared with those in a post-pandemic period (April–September 2023). Results: A total of 5137 newborns were included, with 1709 born during the 6-month pre-pandemic period, 1806 during the 6-month lockdown period and 1687 during the 6-month post-pandemic period. During the pandemic period, significantly fewer patients were hospitalized due to hyperemesis gravidarum (1.8% vs. 0.9%, p = 0.04). No differences were observed concerning the incidence of miscarriages before and after 14 weeks of gestation (WG), preterm deliveries (<37 WG), gestational age at preterm birth and birth weight. Likewise, within the group of preterm-born babies, no difference was observed in preeclampsia among the two periods. However, in the pandemic period, the frequency of preterm-born babies with suspected FGR was significantly lower than in the pre-pandemic period (1.5% and 0.6%, p = 0.01). Regarding this point, we analyzed data of all newborns in a comparative post-pandemic period in 2023 (n = 1687). This group presented a significantly increased FGR incidence compared to that during the pandemic, therefore returning to the pre-pandemic level (1.5% and 1.4%, p = 0.145). Conclusions: During the COVID-19 pandemic, there were significantly fewer deliveries with suspected FGR. After all specific restrictions on elective and outpatient services were lifted, the incidence of suspected FGR returned to its initial level, suggesting that the diagnosis—as a solely machine-dependent and not symptom-based diagnosis—was partly exaggerated in both the pre-and post-pandemic periods. Full article

Background: Pre-pregnancy overweight and obesity are established risk factors for adverse maternal and perinatal outcomes in the general obstetric population. However, data regarding their impact in female liver transplant recipients remain limited. This study aimed to evaluate the association between pre-pregnancy body mass index (BMI) and pregnancy-related complications and neonatal outcomes in this high-risk cohort. Methods: A retrospective cohort analysis was conducted on pregnancies in liver transplant recipients who delivered between 2001 and 2022 at a single tertiary referral center. Participants were stratified into two groups based on pre-pregnancy BMI: normal weight (18.5–24.9 kg/m²) and overweight/obese (≥25 kg/m²). Maternal characteristics, pregnancy complications, and perinatal outcomes were compared using appropriate statistical methods, with significance set at p < 0.05. Results: Among 72 pregnancies included in the analysis, 48 (66.7%) were in women with normal BMI, and 24 (33.3%) were in those with an elevated BMI. No statistically significant differences were observed in gestational age at delivery, neonatal birth weight, Apgar scores, or incidence of preterm birth. Although pregnancy-induced hypertension and cesarean delivery were more prevalent among overweight/obese individuals, these differences did not reach statistical significance (PIH: 28% vs. 10.4%, p = 0.112; cesarean delivery: 76% vs. 64.6%, p = 0.465). Conclusions: In conclusion, pre-pregnancy overweight and obesity were not significantly associated with adverse obstetric or neonatal outcomes in liver transplant recipients. Nevertheless, the observed trends suggest a potential predisposition to hypertensive disorders (PIH: 28% vs. 10.4%, p = 0.112), underscoring the importance of individualized preconception counseling and weight optimization strategies in this high-risk patient population. Full article

Background/Objectives: Long non-coding RNAs (lncRNAs) play a crucial role in trophoblast invasion, immune tolerance, and placental angiogenesis. To delineate their diagnostic and pathological significance, we critically evaluated the evidence for correlations between circulating or placental lncRNA profiles with pregnancy complications. Methods: Five databases were searched from inception through September 2024. We included only the studies that assessed the expression of the lncRNA-complicated pregnancies versus a control group. Results: Three single-center case–control studies fulfilled the inclusion criteria. Eight serum lncRNAs that present <20 weeks of gestation were elevated in subsequent pregnancy-induced hypertension or preeclampsia. The three lncRNAs in intrahepatic cholestasis of pregnancy were consistently decreased with a negative correlation with bile acids. Gestational diabetes was characterized by the elevation of MALAT1. Conclusions: Different lncRNAs showed a potential for use as non-invasive markers as well as for risk stratification for pregnancy-induced hypertension or preeclampsia, metabolic, and hepatobiliary pregnancy complications. There is a need for large-scale, multi-ethnic, prospective cohorts to include lncRNA as screening or therapeutic targeting in obstetric practice. Full article

Preeclampsia (PE), a major cause of perinatal morbidity and mortality, is frequently under-recognized as an early indicator of future cardiovascular (CV) disease. This study examines early-onset preeclampsia (eoPE) across three phases—pre-pregnancy, diagnosis, and follow-up—to dynamically reclassify risk of eoPE in the second-trimester and assess long-term CV implications. A case-control study involving 50 women with eoPE (diagnosed before 34 weeks) and 50 matched controls with uncomplicated pregnancies employed supervised machine learning to develop two predictive models: one for reevaluating first-trimester eoPE risk, with test sensitivity/specificity of 95.0% (92.2–97.8%)/99.0% (97.6–100.0%) and another for predicting post-pregnancy hypertension (HT), with test sensitivity/specificity of 74.1% (67.2–80.9%)/89.1% (85.5–92.8%). Metaheuristic methods identified key features for risk reevaluation and prediction, achieving high predictive performance using routine early pregnancy data and diagnostic information. These findings should be interpreted with caution due to the sample size limitations. Additionally, unsupervised machine learning on follow-up data (median 7.5 years postpartum) was used to explore how pregnancy conditions shape long-term health in eoPE patients. Full article

Background/Objectives: While clinical guidelines recommend screening and treatment for gestational diabetes mellitus (GDM) between 24 and 28 weeks, the benefits of earlier diagnosis are emerging. The objective of this study was to evaluate whether the early diagnosis of GDM is associated with reduced excessive gestational weight gain (GWG). Methods: Cohort study that analyzed 4694 pregnant women diagnosed with GDM attending high-risk prenatal care services within the Brazilian Unified Health System in six Brazilian capitals. GWG was classified according to Brazilian-specific pregnancy recommendations. ANCOVA tests were used to compare mean differences in total GWG across the timing of diagnosis. The timing of GDM diagnosis and excessive GWG was further evaluated using linear and logistic regression analysis. Results: Among the 4694 women with GDM (mean age 31.7 ± 6.3 years; mean pre-pregnancy BMI 30.4 ± 6.5 kg/m², with 47.6% classified with obesity), those diagnosed in the first trimester (n = 1315) gained 2.29 kg less (95% CI: −2.87 to −1.71 kg) total GWG compared to the third trimester, adjusting for risk factors including pregestational weight. First-trimester GDM diagnosis was associated with 22% lower odds of experiencing excessive GWG (Odds Ratio [OR] = 0.78; 95% CI: 0.72–0.86), compared to the third trimester. Diagnoses before 20 weeks and before 24 weeks had 18% (OR = 0.82; 95% CI: 0.77–0.88) and 19% (OR = 0.81; 95% CI: 0.76–0.87) lower odds of excessive GWG. Conclusions: Early diagnosis of GDM, particularly during the first trimester, is associated with reduced GWG. Integrating earlier GDM screening into routine prenatal care could mitigate excessive GWG. Full article

Background/Objectives: Maternal nutrition and pregestational BMI are critical determinants of pregnancy outcomes. This prospective multicenter observational study investigated the interplay between prepregnancy BMI, dietary patterns, and oxidative/inflammatory status in 153 Italian healthy pregnant women with normal weight (NW), overweight (OW), or obesity (OB). Methods: Detailed clinical, biochemical, placental, and neonatal data were measured at third trimester and delivery. Dietary intake was assessed via a validated questionnaire, and dietary patterns were derived using principal component analysis. Results: OW and OB women had significantly higher levels of inflammatory (CRP, hepcidin) and oxidative stress biomarkers (DNA/RNA damage, catalase activity) than NW. Multivariate models confirmed independent associations between BMI and these biomarkers (CRP: β = 0.297, p = 0.000; hepcidin: β = 1.419, p = 0.006; DNA/RNA damage: β = 409.9, p = 0.000; catalase activity: β = 1.536, p = 0.000). Superoxide dismutase activity and total antioxidant capacity were not associated with BMI. Nutritional intake across BMI groups was largely suboptimal relative to national recommendations, with insufficient levels of polyunsaturated fats and key micronutrients. Four dietary patterns were identified, with adherence varying by BMI. A “prudent-style” pattern (high plant, low animal) was positively associated with gestational age (β = 0.243, p = 0.033) and inversely with neonatal head circumference (β = −0.414, p = 0.050). A “Western-like” pattern (high sugars, snacks, animal fats) was linked to reduced maternal ferritin (β = −2.093, p = 0.036) and increased neonatal head circumference (β = 0.403, p = 0.036). However, not all deviations from the “prudent-style” pattern were metabolically equivalent: while Pattern 3 (high-protein, carbohydrate) may offer partial protective effects, Pattern 4 (moderate protein/plant/sugar) displayed elements of nutritional imbalance with signs of placental inefficiency (β = −0.384, p = 0.023). Conclusions: These findings underscore the dual impact of maternal BMI and diet quality on oxidative-inflammatory balance and perinatal outcomes, supporting the need for early, individualized nutritional strategies in pregnancy. This is further emphasized by the variability in dietary adherence across BMI categories. Full article

Background: Empowerment during pregnancy is linked to improved maternal and infant health outcomes and greater maternal well-being. Group Antenatal Care (GANC), a participant-centered model of care, promotes empowerment, active engagement, and the deconstruction of hierarchy between participants and care providers. It combines health assessment, interactive learning, and community building. While empowerment is a core concept of GANC, the ways it manifests and the elements that facilitate it remain unclear. Method: We conducted a generic qualitative study across four organizations in Brussels, using multiple data collection methods. This included interviews with 13 participants and 21 observations of GANC sessions, combining both the insider and outsider perspective. An adapted version of the Pregnancy-Related Empowerment Scale (PRES) guided the interviews guide and thematic analysis. Results: We identified seven themes that capture how empowerment occurs in GANC: peer connectedness, provider connectedness, skillful decision-making, responsibility, sense of control, taking action, and gaining voice. Several aspects of GANC contribute to empowerment, particularly the role of facilitators. Conclusions: This study highlights how GANC enhances empowerment during pregnancy through interpersonal, internal, and external processes. Important components within GANC that support this process include the group-based format and the interactive nature of the discussions. The presence of skillful GANC facilitators is an essential prerequisite. In a diverse and often vulnerable context like Brussels, strengthening empowerment through GANC presents challenges but is especially crucial. Full article

Human milk bacteria contribute to gut microbiome establishment in breastfed infants. Although breastfeeding is recommended throughout infancy, temporal variation in the milk microbiome—particularly beyond solid food introduction—remains understudied. We analyzed 539 milk samples from 83 mother–infant dyads between 1 week and 12 months postpartum using full-length 16S rRNA gene sequencing. The microbiota was dominated by Streptococcus (34%), Cutibacterium (12%), and Staphylococcus (9%), with marked inter-individual variation. Microbiome profiles remained largely stable across lactation, with only six taxa showing temporal fluctuations, including increases in typical oral bacteria such as Streptococcus salivarius, Streptococcus lactarius, Rothia mucilaginosa, and Granulicatella adiacens. Richness and evenness were higher at 1 week compared to 1 month postpartum (p = 0.00003 and p = 0.007, respectively), then stabilized. Beta diversity also remained stable over time. Maternal pre-pregnancy BMI was positively associated with Gemella haemolysans (p = 0.016), while Haemophilus parainfluenzae was more abundant in milk from mothers with allergies (p = 0.003) and those who gave birth in autumn or winter (p = 0.006). The introduction of solid food was linked to minor taxonomic shifts. Overall, the milk microbiome remained robustly stable over the first year of lactation, with limited but notable fluctuations in specific taxa. This study supports the role of human milk as a consistent microbial source for infants and identifies maternal BMI, allergy status, and birth season as key variables warranting further investigation. Full article