Search Results (722)

Background/Objectives: A third-generation atypical antipsychotic drug, aripiprazole, is known to cross the placental barrier and pose negative consequences on placental growth and the normal development of the fetus. Although a few studies demonstrated these debilitating effects of aripiprazole, its skeletal effects remain unexplored. Therefore, this study was undertaken to evaluate the impact of prenatal aripiprazole exposure, administered at three different dose levels, on the ossification of the appendicular skeleton in 20-day-old rat fetuses. Methods: Forty pregnant Sprague–Dawley rats (n = 40) were assigned to four groups: control and three aripiprazole-treated groups receiving 3 mg/kg (LDA), 6 mg/kg (HDA), and 12 mg/kg (DHDA) daily from gestational days 6–19. Fetuses were delivered on gestation day 20, weighed, and processed for skeletal evaluation using Alizarin Red S staining. Ossification patterns of metacarpals, metatarsals, hip bones, long bones of the forelimb and hindlimbs from a total of 151 fetuses were analyzed and categorized as complete, delayed, or absent. Results: Aripiprazole exposure induced a dose-dependent reduction in the number of completely ossified skeletal bony centers (p < 0.01) with a highly significant reduction in the length of ossified portions of the long bones (p < 0.001). Histomorphometric analysis of Von Kossa-stained fetal femur sections revealed a significant decrease in the thickness of ossified cortical and trabecular bone with a statistically significant reduction in the length of hypertrophied chondrocytes of the growth plate cartilage in the aripiprazole-treated groups (p < 0.05). Conclusions: Prenatal exposure to aripiprazole leads to dose-dependent skeletal growth restriction and delayed ossification of the appendicular skeleton in rat fetuses. Future investigations should focus on the molecular mechanisms and consequences related to the prenatal impact of aripiprazole. Full article

Background and Objectives: Acute cholecystitis occurs in approximately 0.3–0.6% of pregnant women and may pose significant risks to both the mother and the fetus. The condition is most commonly caused by gallstone-induced obstruction of the cystic duct, with pregnancy-related hormonal and physiological changes contributing to its development. The aim of this review was to summarize current evidence on the pathogenesis, diagnostic challenges, and management of acute cholecystitis during pregnancy, as well as to evaluate associated maternal and fetal outcomes. Materials and Methods: This study was conducted as a structured narrative review incorporating elements of a systematic literature search. A comprehensive search was performed in PubMed (MEDLINE), with additional sources identified through Google Scholar. Articles published between 2015 and 2025 were included. Eligible studies addressed pathogenesis, risk factors, diagnosis, management, or maternal and fetal outcomes. A total of 55 studies were included and analyzed qualitatively. Results: Acute cholecystitis during pregnancy presents diagnostic challenges due to nonspecific symptoms that may overlap with normal pregnancy-related conditions. Ultrasound remains the first-line imaging modality. Conservative management is associated with high recurrence and rehospitalization rates, as well as increased risks of adverse fetal outcomes, including preterm delivery, fetal growth restriction, and low birth weight. In contrast, laparoscopic cholecystectomy is associated with lower complication rates and improved outcomes, and can be safely performed during all trimesters when clinically indicated. Conclusions: Acute cholecystitis during pregnancy requires careful clinical evaluation and individualized management. Current evidence suggests that laparoscopic cholecystectomy is a safe and effective treatment option, and is widely considered the preferred approach in most cases. Conservative management may be appropriate in selected mild cases but is associated with a higher risk of recurrence and adverse outcomes. Full article

Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality, yet reliable first-trimester biomarkers for early prediction remain lacking. Growing evidence suggests that placental dysfunction is a central pathological driver of FGR. Therefore, placenta-derived proteins in maternal circulation may serve as mechanistically informative biomarkers for early detection. Here, we aimed to evaluate several placenta-relevant molecules as biomarkers for predicting isolated FGR and its subtypes. In this prospective nested case–control study, we included singleton pregnancies that underwent Down screening in the first trimester and were subsequently diagnosed with FGR (n = 50, including early-onset FGR [EFGR] and late-onset FGR [LFGR]) and healthy pregnancies (n = 100). Pregnancies with maternal comorbidities or fetal anomalies were excluded. Maternal serum protein concentrations were measured using ELISA kits. There were no significant differences in placenta-specific protein 1 (PLAC1) or netrin-1 between the two groups. By contrast, maternal soluble programmed death-ligand 1 (sPD-L1) levels were significantly lower in overall FGR (p < 0.001) and FGR subtypes (p = 0.002) than in controls. Circulating sPD-L1 levels were positively correlated with gestational age at delivery and birth weight Z score. Each one-unit increase in sPD-L1 was associated with lower odds of overall FGR (Odd ratio, OR 0.33), EFGR (OR 0.17), LFGR (OR 0.43), birth weight Z score 3–10% (OR 0.30), and neonatal intensive care unit (NICU) admission (OR 0.38). Moreover, first-trimester sPD-L1 predicted overall FGR (area under the receiver operating characteristic curve, AUC 0.75), EFGR (AUC 0.84), LFGR (AUC 0.70), birth weight Z score 3–10% (AUC 0.75), and NICU admission (AUC 0.67). Collectively, decreased maternal circulating sPD-L1 in early pregnancy may serve as a potential biomarker for isolated FGR, warranting validation in larger multicenter mechanistic studies. Full article

Objective: To investigate clinical, ultrasonographic, and hematological factors associated with cesarean delivery due to intrapartum fetal compromise in pregnancies complicated by isolated late-onset fetal growth restriction (FGR) undergoing induction of labor at 37 weeks of gestation. Methods: This retrospective cohort study included singleton pregnancies with isolated late-onset FGR undergoing elective induction of labor between 37 + 0 and 37 + 6 weeks of gestation. Patients who underwent cesarean delivery due to intrapartum fetal compromise constituted the study group (n = 44), whereas those who achieved vaginal delivery formed the control group (n = 100). Maternal demographic characteristics, fetal ultrasonographic findings, and systemic inflammatory indices were evaluated. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results: Gravidity, parity, induction-to-birth interval, cervical dilatation at admission, femur length, and platelet count differed significantly between the groups. In multivariable logistic regression analysis, parity remained the only independent predictor of cesarean delivery due to intrapartum fetal compromise (adjusted OR 0.421, 95% CI 0.191–0.926, p = 0.031). Systemic inflammatory indices and most fetal ultrasonographic parameters did not demonstrate independent predictive value. The combined multivariable model demonstrated acceptable discriminative performance (AUC 0.731, 95% CI 0.636–0.827, p < 0.001). Neonatal outcomes were comparable between the groups. Conclusions: In pregnancies complicated by isolated late-onset FGR undergoing induction of labor at 37 weeks, parity was the only independent predictor of cesarean delivery due to intrapartum fetal compromise. Routine clinical, ultrasonographic, and hematological inflammatory markers demonstrated limited independent predictive value. These findings suggest that intrapartum fetal compromise in FGR pregnancies may primarily reflect reduced fetoplacental reserve rather than isolated antenatal parameters. Full article

First-trimester sonographic examination remains a fundamental part of antenatal care, providing crucial information for the well-being of both the mother and fetus and leading to the best possible perinatal outcomes. This study aimed to review and compare the most recently published guidelines on first-trimester ultrasound. Therefore, a descriptive review of guidelines from the American Institute of Ultrasound in Medicine (AIUM), the Australasian Society of Ultrasound in Medicine (ASUM), the Association of the Scientific Medical Societies in Germany (AWMF), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the Society of Obstetrician and Gynecologists of Canada (SOGC) and the World Association of Perinatal Medicine (WAPM) regarding first-trimester scans was conducted. There is a consensus regarding the main parameters that should be evaluated, the qualifications of the examiner and specifications of the ultrasound machine, as well as the importance of informed consent. Additionally, the importance of careful visualization of fetal anatomy is discussed, with minor discrepancies regarding the appropriate protocol used. The use of combined first-trimester examination is encouraged by all the reviewed medical societies, although cell-free DNA testing is addressed only by a few, with similar indications. Controversy exists regarding the indications and appropriate gestational age at which the first-trimester scan should be performed, as well as the proper establishment of pregnancy dating. Notably, recommendations regarding fetal growth restriction (FGR) and diagnostic invasive procedures are made only by few medical societies, with the AWMF and SOGC addressing screening for FGR. Furthermore, invasive diagnostic testing is discussed by the AIUM, AWMF and SOGC, with differentiations among them regarding the indications for pursuing such procedures. First-trimester sonographic examination is essential for assessing fetal viability, establishing accurate pregnancy dating, evaluating fetal and maternal anatomy and calculating the risk of various fetal and maternal conditions. The implementation of evidence-based, unified protocols would advance both maternal and fetal outcomes. Full article

Preeclampsia (PE) is a severe pregnancy-specific hypertensive disorder characterized by immune microenvironment dysregulation at the maternal–fetal interface, with decidual macrophage phenotypic imbalance being a key pathological feature. The Ghrelin/growth hormone secretagogue receptor-1a (GHSR-1a) axis exerts immunomodulatory and anti-inflammatory effects, but its role in regulating decidual macrophage infiltration and phenotypic marker expression in PE remains unclear. In this study, we first detected the expression of the Ghrelin/GHSR-1a axis in decidual tissues from 10 healthy pregnant women and 12 PE patients via immunohistochemistry (IHC). We then established a lipopolysaccharide (LPS)-induced PE-like rat model to investigate the axis’s functional role and underlying mechanisms. Intriguingly, clinical analysis revealed a severity-dependent compensatory escalation of the Ghrelin/GHSR-1a axis in PE decidual tissues, potentially representing an endogenous antagonistic response to pregnancy-associated pathological stress. In the animal model, exogenous Ghrelin supplementation reversed LPS-induced PE-like phenotypes, including hypertension, proteinuria, fetal growth restriction (FGR), and placental dysfunction, and alleviated pathological damage to the maternal liver, kidney, and placenta. Mechanistically, Ghrelin modulated decidual macrophage phenotypic marker expression by downregulating the M1 marker CD86 and upregulating the M2 marker CD163 and promoted trophoblast invasion and spiral artery remodeling by restoring laminin, α-cytokeratin 7 (α-CK7), and α-smooth muscle actin (α-SMA) expression in placental tissue. All protective effects of Ghrelin were abrogated by co-administration of D-lys-3-GHRP-6, a specific GHSR-1a antagonist, confirming the dependence on the Ghrelin/GHSR-1a axis. Collectively, our findings suggest that the Ghrelin/GHSR-1a axis is compensatorily upregulated in PE and may exert a protective role by regulating decidual macrophage phenotypic marker expression and improving placental function, providing preliminary evidence that this axis merits further investigation as a potential research target for PE. Full article

Background/Objectives: Sleep breathing disorders (SBDs) comprise a range of conditions characterized by abnormal respiratory patterns during sleep, with obstructive sleep apnea (OSA) being the most common. During pregnancy, SBDs are of clinical relevance, as they are associated with increased maternal and neonatal morbidity. Methods: A structured literature search was conducted to identify relevant studies addressing sleep breathing disordered in pregnancy, including longitudinal, observational, case-control, and cross-sectional studies, as well as other reviews and meta-analyses. Results: Adequate sleep during pregnancy is essential for maternal health and fetal development. OSA in pregnant women is strongly associated with hypertensive disorders of pregnancy (HDPs), potentially contributing to increased long-term cardiovascular risk. In addition to hypertensive complications, OSA has been linked to gestational diabetes and postpartum depression. Untreated SBDs may also have consequences beyond pregnancy, adversely affecting fetal and neonatal outcomes. Pathophysiological mechanisms related to maternal SBDs can result in fetal growth restriction, impaired neurocognitive development, and an increased risk of preterm birth. Conclusions: Current evidence indicates that OSA during pregnancy is associated with elevated short- and long-term risks for both mothers and offspring. Future research should prioritize large prospective studies with standardized diagnostic criteria and outcomes, as well as pragmatic trials to assess the implementation of SBD screening in prenatal care, particularly among high-risk populations such as obese women. Full article

Importance: Immune checkpoint inhibitors (ICIs) have transformed the management of cancers affecting reproductive-age patients, yet their impact on pregnancy outcomes remains incompletely understood. We describe two cases of maternal and fetal outcomes associated with ICI exposure during pregnancy and present a comprehensive literature review. Methods: A retrospective chart review was conducted at MD Anderson Cancer Center (1 January 2015 to 31 December 2024) to identify patients exposed to ICIs during pregnancy. Clinical data including cancer type, treatment timing, pregnancy course, and maternal and neonatal outcomes were collected. A narrative literature review was also performed using PubMed to identify reported cases of ICI exposure during pregnancy. Observations: Two patients were identified at our institution, both treated with ICIs for advanced melanoma. One patient received pembrolizumab during early pregnancy, with the final dose administered five days after conception, and subsequently gave birth to a healthy term infant without complications. The second patient conceived while receiving adjuvant nivolumab and experienced a miscarriage at 13 weeks of gestation. Neither patient experienced immune-related toxicity during pregnancy, and both remained without evidence of disease at follow-up. The literature review identified 21 reported pregnancies with ICI exposure and variable outcomes. Most resulted in live births (85.7%), though preterm delivery occurred in approximately 50% of cases, often due to maternal or fetal indications. Additional reported outcomes included miscarriage, neonatal death, fetal growth restriction, preeclampsia, and rare immune-related neonatal effects. Congenital anomalies were reported in a small number of cases. Conclusions and Relevance: These findings suggest that, while many pregnancies exposed to ICIs result in live births, there may be an increased risk of adverse maternal and fetal outcomes. However, causality cannot be established due to the limited quality and quantity of available data. These findings underscore the importance of effective contraception during ICI therapy and careful multidisciplinary counseling when exposure occurs during pregnancy. Full article

Fetal growth restriction (FGR) is frequently defined as the failure of the fetus to reach its genetically predetermined growth potential. Heat shock proteins (HSPs) are extreme-temperature-resistant molecules that help proteostasis. The aim of this prospective case–control immunohistochemistry study is to evaluate the expression of HSP90 and HSP70 in the placentas of pregnancies complicated with FGR and compare their levels with the control placentas of normal-growth pregnancies. A prospective case–control study was conducted including people undergoing singleton pregnancies who gave birth in a tertiary university hospital in Central Greece. Participants were divided into two equal groups: an FGR pregnancy group and a control group with normal growth. Immunohistochemistry of placental samples was assessed using anti-HSP90 alpha/beta antibody (clone F-8, Santa Cruz Biotechnology, Dallas, TX, USA) and anti-HSC70/HSP70 antibody (clone W27, sc-24, Santa Cruz Biotechnology, Dallas, TX, USA). A scoring system was created to quantify the expression of HSP90 and HSP70 in each sample, and the grade of staining was measured at four points. A total of 80 pregnant people were prospectively enrolled in our study, with 40 in each group. Both constitutive (HSP90β and HSC70/HSPA8) and stress-inducible (HSP90α and HSP70/HSPA1A/B) isoforms were analyzed. When comparing the total score of HSP expression, a statistically significant difference was observed for both HSP90 and HSP70. For HSP90 expression, only the Hofbauer cell’s stain was identified as a statistically significant independent factor, meaning that its positive expression was observed in Hofbauer cells. For HSP70 expression, only the staining of syncytiotrophoblasts was identified as an independent factor. FGR is a common pregnancy complication and a leading cause of stillbirth, neonatal mortality, and short- and long-term neonatal morbidity worldwide. Based on our findings, the lower expression levels of both HSP90 and HSP70 are associated with FGR, revealing a possible association with stress response in FGR pathophysiology. However, more robust data from larger-scale prospective studies are needed to elucidate the possible role of HSPs as potential FGR biomarkers. Full article

Background: Micro- and nano-plastics (MNPs) are pervasive environmental contaminants that accumulate in various tissues, including the placenta. Experimental and clinical studies suggest potential cytotoxic, oxidative, and inflammatory effects that may lead to placental dysfunction and adverse obstetric outcomes. However, high-quality evidence on the clinical relevance of MNPs exposure during pregnancy remains scarce, underscoring the need for systematic evaluation of their impact on maternal and fetal health. Methods: The databases PubMed, ScienceDirect, CENTRAL, Embase, MDPI and Google Scholar were searched for studies published up to September 2025 investigating the relationship between MNPs and obstetric outcomes. Results: Twelve studies were included in this review, with half employing an observational design in human subjects and the other half using experimental studies in murine models. Although the available evidence is limited, there are studies reporting the association between MNPs exposure and premature birth, low birth weight, intrauterine growth restriction, and miscarriage. The most prevalent polymer detected was polyethylene, and the most commonly used MNPs detection techniques were Raman microspectroscopy, digital microscopy, Fourier Transform Infrared, and Pyrolysis gas chromatography-mass spectrometry. Conclusions: This systematic review summarizes current limited insights on the potential effects of MNPs on obstetric outcomes, highlighting possible associations with low gestational age, low birth weight, intrauterine growth restriction, and miscarriage. Findings do not allow causal inference due to heterogeneity in study design, exposure assessment, contamination control, and analytical methodologies. Full article

Pathologic pregnancies including recurrent pregnancy loss, stillbirth, early-onset pre-eclampsia and early-onset fetal growth restriction form a continuous spectrum throughout gestation and have attracted wide attention. Autoimmune disorders and associated acquired thrombophilia are key etiological factors. However, because of the complicated associations between various clinical manifestations, laboratory examinations and treatments, the management of pathologic pregnancies with autoimmune disorders and associated acquired thrombophilia are difficult. This viewpoint article presents a comprehensive full gestation management strategy emphasizing early identification and multidisciplinary management to improve pregnancy outcomes in these patients. Future research should focus on novel biomarkers, therapeutic methods and crosstalk mechanisms between autoimmune disorders and thrombophilia to optimize clinical strategies. Full article

Background: Infection and inflammation are key contributors to spontaneous preterm birth (PTB), but the relationship between genitourinary microbial colonization and placental inflammatory pathology across preterm subgroups remains unclear. Methods: In this case–control study, women with PTB were compared with gestational age-matched controls. Urine cultures, Mycoplasma/Ureaplasma screening, inflammatory markers, and placental histopathology were analyzed. Early (24–33 weeks) and late (34–36 weeks) preterm births were evaluated separately. Results: Clinical risk factors were more common in PTB cases (87.0% vs. 68.7%, p = 0.001), particularly PPROM and fetal growth restriction. Conventional urine culture positivity did not differ between groups. Mycoplasma/Ureaplasma colonization was more frequent in controls (41.2% vs. 15.4%, p < 0.001). Early PTB was strongly associated with placental inflammation, including higher rates of histological chorioamnionitis, composite inflammatory lesions, placental culture positivity, and elevated CRP compared with late PTB. Conclusions: Early PTB may represent a distinct infection-associated phenotype characterized by prominent placental inflammation, whereas late PTB demonstrates a weaker inflammatory profile. Full article

Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorder (FASD). The FASD continuum encompasses facial dysmorphism, growth failure, and central nervous system (CNS) abnormalities/dysfunctions. Because some of these features may not be apparent in newborns, detecting PAE in the neonatal period is challenging, while early diagnosis may improve neurodevelopmental outcomes. Maternal self-reported alcohol consumption is limited by recall bias and denial, leading to misdiagnosis. Currently, there is a lack of universally implemented and standardized tools for identifying PAE/FASD in children across clinical settings. We aimed to review the existing literature on PAE assessment methods. Analysis of alcohol metabolites in neonatal meconium is the most widely studied and appears to be feasible for routine use, but it has some limitations. Recent advances in understanding the effects of alcohol on neurotransmitters, growth factors, and gene activity have contributed to the development of novel diagnostic strategies and have brought us closer to effective PAE detection. Some laboratory assays appear to be feasible for implementation in routine clinical practice, i.e., testing for pro- and anti-inflammatory cytokines, including interleukins (IL): IL-6, IL-1β, IL-10, and tumor necrosis factor-alpha (TNF-α) and Insulin-like Growth Factor 1(IGF1). These molecular approaches hold promise but require replication and validation before becoming the standard in clinical practice. Further research on biomarkers and other screening tools should continue to determine their feasibility and availability. Full article

Nutrient restriction (NR) increases small-for-gestational-age (SGA) offspring; however, some NR ewes deliver Non-SGA lambs. We evaluated whether fetal biometry and Doppler indices could distinguish divergent fetal growth trajectories. Ninety-five single-pregnant Corriedale ewes were assigned to NR grazing (n = 72) or supplemented Controls (n = 23) from gestational day (GD) 70 to 140. Fetal biparietal diameter (BPD), femur length (FL), thoracic height (TH), umbilical cord diameter (UCD), and resistance (RI) and pulsatility (PI) indices in umbilical (UA), cotyledonary (CA), and uterine (UtA) arteries were assessed at several GDs. Offspring within NR group was stratified by birth weight (BW) quartiles as SGA (n = 18) or Non-SGA (n = 18). At birth, BW differed (p < 0.05) among Control (4.95 ± 0.10 kg), Non-SGA (5.33 ± 0.06 kg), and SGA (3.79 ± 0.11 kg), with reduced BPD and FL in SGA lambs. Prenatal biometry did not differ. UA-RI at GD125 was higher in SGA (p < 0.005) and associated with BW (R² = 0.15; p < 0.001). UtA indices were lower in SGA at GD110 and GD125 (p < 0.05) but weakly associated with BW (R² ≤ 0.08). Doppler differences were detected before measurable growth divergence but have modest predictive value. Full article

Objective: To evaluate and compare fetal arterial and venous Doppler parameters in early-onset (EO) and late-onset (LO) fetal growth restriction (FGR), and to assess their performance within the study cohort and their association with composite adverse neonatal outcome (CANO). Methods: This prospective observational cohort study included 184 singleton pregnancies between 24 and 37 weeks of gestation, comprising 91 FGR cases and 93 appropriate-for-gestational-age controls. FGR was defined according to Delphi consensus criteria and classified as EO-FGR (<32 weeks) or LO-FGR (≥32 weeks). All fetuses underwent standardized Doppler assessment of the umbilical artery (UA), middle cerebral artery (MCA), uterine artery (UtA), and ductus venosus (DV). The cerebroplacental ratio (CPR) was calculated. Multivariable logistic regression models were constructed separately for EO-FGR and LO-FGR. Classification performance was evaluated using receiver operating characteristic analysis. CANO was defined as at least one of the following: 5-min Apgar score <7, respiratory distress syndrome, neonatal intensive care unit admission, or preterm birth. Results: In both EO-FGR and LO-FGR, UA PI values were significantly higher, whereas MCA PI and CPR were significantly lower than in controls. CPR demonstrated the highest discriminative performance among arterial parameters in both subgroups. DV Doppler indices were not significantly different in EO-FGR. In LO-FGR, DV S-wave and v-wave velocities were independently associated with FGR. No significant associations were observed between Doppler parameters and CANO in subgroup analyses. Conclusions: Arterial Doppler parameters, particularly CPR, showed consistent alterations in both EO- and LO-FGR. The contribution of venous Doppler parameters differed according to clinical subtype, with additional value observed in LO-FGR. Full article