Search Results (386)

Background: The definitions and approaches used to diagnose gestational diabetes (GD) are varied. The two-step approach recommended by the American College of Obstetricians and Gynecologists (ACOG) combines the sensitivity of a glucose challenge test (GCT) with the specificity of a 3-hour oral glucose tolerance test (OGTT). We investigated if minor modification of the two-step procedure can provide improved detection of GD by identifying a risk group of pregnant women with high risk of GD. Methods: We conducted a prospective cohort study of pregnant women enrolled early during pregnancy and followed till delivery. All participants underwent the ACOG-recommended two-step procedure for GD diagnosis. Based on GCT and OGTT results, the participants were divided into four risk groups (RGs): GCT-negative (RG0), GCT-positive but OGTT normal (RG1), single abnormal value on OGTT or raised HbA1c (RG2) and diagnosed GD (RG3). Baseline evaluation included dietary history (24 hour recall) and physical activity. A series of multivariable logistic regression analyses were conducted to estimate the odds of maternal and fetal outcomes. Results: A total of 1041 pregnant women were included in the study, of whom 16 (1.6%) were diagnosed as GD. Our two-step approach identified 48 (4.6%) women as GD, while RG2, RG1 and RG0 comprised 75 (7.2%), 218 (20.9%) and 700 (67.2%), respectively. Compared to RG0, RG2 showed a higher likelihood of antepartum complications [odds ratio and 95% confidence interval 2.38 (1.16–4.15)], any adverse outcome without [2.04 (1.17–3.55)] or with cesarean section [2.09 (1.21–3.61)] and primary cesarean section [1.68 (1.01–2.81)] after adjustment for potential confounders. RG2 was also significantly associated with pregnancy-induced hypertension, meconium-stained amniotic fluid and premature rupture of membranes. Conclusions: In the study participants, we identified a subgroup (RG2) at high risk of GD with perinatal outcomes showing profile consistent with that of GD. Full article

Background: Preterm birth (PTB) remains a leading cause of neonatal morbidity and mortality worldwide. Inflammatory cytokines, particularly IL-6, are central to PTB pathogenesis. Lactoferrin (LF), an iron-binding glycoprotein with antimicrobial and immunomodulatory properties, has been proposed as a potential protective factor against PTB. This narrative review aimed to synthesize current evidence on LF supplementation and its effects on inflammation, cytokine modulation, biochemical markers, and obstetric outcomes related to PTB. Methods: Eight clinical studies involving pregnant women at risk of PTB were included. LF was administered orally, vaginally, or through combined regimens, with variations in dosage and duration. Reported outcomes encompassed inflammatory markers, cervical and uterine parameters, oxidative stress biomarkers, and obstetric or neonatal endpoints. Results: Across the studies, LF supplementation was consistently associated with reduced pro-inflammatory cytokines, improvements in cervical length and uterine activity, and favorable changes in oxidative stress markers. Clinically, supplementation was linked with prolonged gestation, fewer preterm births, and reduced neonatal intensive care admissions. Immunological analyses further suggested a positive modulation of cytokine profiles in amniotic fluid. Conclusions: LF appears to exert multifaceted immunomodulatory effects that mitigate inflammation and support pregnancy maintenance. Although findings point to its potential role in PTB prevention, they should be interpreted with caution given the limited and heterogeneous evidence. Further large-scale, multicenter randomized trials are needed to confirm efficacy and to establish optimal dosage, route, and timing of administration. Full article

Background/Objectives: Alcohol and smoking during pregnancy may be associated with several complications, but the underlying mechanism is still unclear. The aim of this study was to evaluate the role of oxidative stress induced by smoking and alcohol during pregnancy and their effects on fetal and neonatal outcomes. Material and methods: We considered pregnant women at term. Validated questionnaires were used to investigate smoking and alcohol habits. Ultrasound was performed to evaluate fetal weight, amniotic fluid index, and maternal-fetal Doppler velocimetry. At the time of delivery, we collected a tuft of maternal hair, maternal venous blood, and cord blood. In these samplings we determined in phase I nicotine, cotinine, and ethyl glucuronide on the maternal keratin matrix with the gas chromatography-mass spectrometry technique. In phase II, the Free Oxygen Radicals Test (FORT) and Free Oxygen Radical Defense (FORD) test were used to assess circulating reactive oxygen species (ROS). Results: 119 pregnant patients were enrolled (n = 62 for smoking and n = 57 for alcohol). Twenty-six patients (42%) out of 62 were active smokers. Three patients (5%) out of 57 were alcoholic consumers. Mean neonatal weight and mean placental weight were significantly lower for active smokers (p = 0.0001). The neonatal weight was in the 1st–2nd percentile for all alcohol abusers. Considering two subgroups (n = 10 non-smokers and n = 10 smokers) for ROS determination, a statistically significant higher oxidative stress in the blood of smoking patients was evidenced (p < 0.0001). In cord blood the differences were not statistically significant (p = 0.2216). Conclusions: Fetal growth restriction was present in the group of active smokers and in patients with alcohol abuse. Oxidative stress was higher in smoking patients than in non-smokers. However, in cord blood, FORT was negative in all cases, suggesting a protective mechanism in utero. Given the limited sample size, the results obtained are preliminary and require future studies. Full article

Objective: To evaluate the predictive value of umbilical artery half peak systolic velocity deceleration time (UA hPSV-DT) for composite adverse perinatal outcomes (CAPO) in pregnancies complicated by gestational diabetes mellitus (GDM). Methods: In this prospective observational study, 120 singleton pregnancies in the third trimester were enrolled: 30 insulin-regulated GDM (IRGDM), 30 diet-regulated GDM (DRGDM), and 60 healthy controls. UA hPSV-DT and standard Doppler indices were measured using a standardized protocol by a single perinatologist. An abnormal UA hPSV-DT was defined as <5th percentile for gestational age. Maternal metabolic parameters, fetal biometry, and neonatal outcomes were recorded. The primary outcome was CAPO, defined as the presence of one or more adverse perinatal events. Results: Median UA hPSV-DT values were significantly lower in IRGDM (171 ms) and DRGDM (184 ms) compared with controls (227 ms) (p = 0.006). Abnormal UA hPSV-DT occurred in 43.3% of GDM cases and was associated with higher estimated fetal weight and abdominal circumference percentiles, increased amniotic fluid, elevated OGTT values, higher HbA1c, and more frequent insulin therapy (p < 0.01 for all). In GDM pregnancies, CAPO occurred in 73.1% of the abnormal UA hPSV-DT group versus 11.8% of the normal group (p < 0.001). ROC analysis identified a cut-off of < 181 ms for predicting CAPO (AUC 0.741, 70.3% sensitivity, 66.7% specificity). Conclusions: UA hPSV-DT is a novel, reproducible Doppler parameter that independently predicts adverse perinatal outcomes in GDM pregnancies, even when conventional UA Doppler indices are normal. Incorporating UA hPSV-DT into routine surveillance may improve risk stratification and guide management to optimize perinatal outcomes. Full article

Complications during pregnancy and parturition can lead to foetal hypoxia, which may be responsible for cardiac ischemia and the subsequent release of troponin from cardiac muscles into the amniotic fluid (AF) and bloodstream. So far, cardiac troponin T (cTnT) has only been measured in the blood samples of adult dogs, while no data on its presence and relevance in AF are available. This study aimed to determine whether cTnT can be detected in canine AF collected at birth. Furthermore, a possible correlation between amniotic cTnT concentration and maternal and neonatal outcomes was explored. For this purpose, 40 AF samples were collected from 14 bitches at the time of delivery. A commercially available ELISA kit was used for the analysis of canine cTnT in biological fluids. Cardiac troponin T was detected in all amniotic specimens with concentrations ranging from 74.1 to 318 ng/L (191.6 ± 66.4 ng/L). The dams’ morphotype, age, and weight, as well as the type of parturition (elective vs. emergency C-section) and the expulsion time of puppies, were significantly associated with amniotic cTnT concentrations. Although amniotic cTnT warrants further investigation to fully understand its clinical role in canine neonatology, these results suggest a promising and valuable contribution. Full article

(1) Background: Fungal infections of amniotic fluid, especially those caused by Candida spp., are rare but clinically important, as they can be correlated with preterm birth and poor neonatal outcomes. The aim of this study was to assess the antifungal susceptibility of Candida spp. isolated from amniotic fluid using an MIC (minimum inhibitory concentration)-based assay. (2) Methods: Forty consecutive, exploratory Candida isolates were identified from amniotic fluid samples at the “Cuza Vodă” Clinical Hospital of Obstetrics and Gynecology, Iași, and were analyzed successively using Sabouraud agar, the VITEK^® 2 Compact system, and real-time PCR (RT-PCR). (3) Results: C. albicans was the most abundant species (67.5%), followed by Pichia kudriavzevii, Nakaseomyces glabratus, C. parapsilosis, and C. dubliniensis. Fluconazole resistance was observed in two C. albicans isolates, emphasizing the clinical importance of routine antifungal susceptibility testing, and all C. albicans isolates were resistant to micafungin, while amphotericin B remained effective against all isolates. RT-PCR confirmed the presence of C. albicans DNA. (4) Conclusions: The detection of resistant Candida strains highlights the importance of conducting assessments at the species level, which could help clinicians to ensure better antifungal stewardship. Full article

Background: Abiogenesis is hypothesized to have occurred in the aquatic environments of the early Earth approximately 3.8–4.0 billion years ago, in oceans containing high concentrations of ions (Na⁺ ≈ 470 mmol/L, Cl⁻ ≈ 545 mmol/L, Mg²⁺ ≈ 51–53 mmol/L, Ca²⁺ ≈ 10 mmol/L, K⁺ ≈ 10 mmol/L, SO₄²⁻ ≈ 28–54 mmol/L, HCO₃⁻ ≈ 2.3 mmol/L). Primitive membranes evolved ion-regulatory mechanisms to sustain electrochemical gradients, enabling metabolic activity. Objectives: This review compares the composition of amniotic fluid (AF) to seawater, framing AF as a “biological ocean” for the fetus, and evaluates the impact of micro- and nanoplastics (MNPs) on this protected milieu. Methods: We synthesized data from published studies on concentrations of and ions and other important substances in AF during pregnancy and compared them with marine values. Reports of MNPs detected in placenta, AF, and human organs were systematically reviewed. Results: AF exhibits high ionic similarity to seawater, although the absolute concentrations of ions are lower, reflecting evolutionary conservation. Recent analytical studies identified MNPs in samples of human placenta (4–10 particles per 1 g of tissue), meconium (median 3–5 particles per g), and AF (detectable in >60% of tested samples). Co-exposure to heavy metals, persistent organic pollutants, and endocrine disruptors were reported in 20–40% of maternal–fetal samples. Conclusions: The analogy between oceans and AF underscores a conserved evolutionary continuum. However, the infiltration of MNPs into intrauterine environments is a novel toxicological challenge with potential implications for neurodevelopment, immune programming, and epigenetic regulation. Within the One Health framework, protecting AF from anthropogenic contaminants is as critical as safeguarding marine ecosystems. Full article

Introduction: Fetal Inflammatory Response Syndrome (FIRS) is widely acknowledged for its contribution to neonatal morbidity in premature infants. Being a systemic inflammatory process triggered by intrauterine infections or other stimuli, FIRS has gained significant attention due to its complex implications for neonatal adverse outcomes: preterm birth, early onset neonatal sepsis, death or long-term neurodevelopmental impairments. Fetal plasma Interleukin-6 (IL-6) levels above 11 pg/mL define FIRS and serve as an essential biomarker, providing insights into the complex mechanisms underlying this response. This study aims to evaluate the clinical, laboratory, and therapeutic differences between preterm neonates with and without FIRS. Methods: A prospective cohort study was conducted, involving 125 preterm neonates with gestational ages between 23 and 37 weeks, who were admitted to the Neonatal Intensive Care Unit (NICU) at the Emergency University Hospital Bucharest between April 2023 and April 2025. Infants were stratified into FIRS and non-FIRS groups based on the measurement of cord blood IL-6 levels greater than 11 pg/mL. Demographic, biochemical, and therapeutic parameters were compared across the two groups. Results: Preterm neonates with FIRS had significantly lower birth weight, length, and head circumference, and lower Apgar scores at 1 and 5 min (p = 0.001). FIRS was associated with a higher incidence of vaginal delivery, meconium-stained amniotic fluid, and neonatal metabolic imbalances, requiring more respiratory support, longer antibiotic treatment periods, and more blood transfusions (p < 0.05). Neonatal complications such as early-onset sepsis (EOS) and late-onset sepsis (LOS), respiratory distress, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP) were significantly more frequent in the FIRS group (p ≤ 0.01). Among maternal cervical screening, Chlamydia trachomatis was the only pathogen significantly associated with FIRS. Conclusions: FIRS in preterm neonates is linked to important perinatal inflammation, adverse short and long-term outcomes, and extensive medical intervention. These findings highlight the value of early identification of intrauterine inflammation and targeted neonatal monitoring strategies. Further studies are needed to explore long-term outcomes and improve diagnostic and therapeutic protocols. Full article

Primary or recurrent infection of cytomegalovirus (CMV) in pregnant women may cause transplacental transmission to fetuses. We aimed to investigate the rate of transplacental CMV transmission in women with positive anti-CMV IgG and negative anti-CMV IgM and its impact on newborns. Pregnant women with positive anti-CMV IgG and negative anti-CMV IgM during the first or second trimester who delivered by Cesarean section were included. Amniotic fluid collected during the Cesarean section was tested for CMV DNA with quantitative real-time polymerase chain reaction. CMV IgG and IgM were measured with enzyme-linked immunosorbent assay. A total of 695 pregnant women were enrolled between April 2019 and February 2023. Of them, 567 (81.6%) were single pregnancies and 128 (18.4%) were twin pregnancies, and 594 (85.5%) were full-term pregnancies and 101 (14.5%) were premature pregnancies. Of the 823 newborns, 7 (0.9%) were CMV DNA positive in amniotic fluid, demonstrating the transplacental CMV transmission. One of these seven neonates was diagnosed with intrauterine growth restriction at gestation week 25⁺¹ and at birth at a gestational age of 30⁺² weeks. However, all seven children had normal hearing, vision, and neurodevelopment at the age of 18–56 months. Transplacental CMV transmission may occur in offspring of pregnant women with positive anti-CMV IgG and negative anti-CMV IgM, but the long-term sequelae appear to be minimal. Full article

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common reversible liver disorder linked to pregnancy, characterised by pruritus and elevated serum bile acids (BAs). Condition severity correlates with increased maternal and neonatal complications, and recent evidence highlights a significantly elevated risk of adverse perinatal outcomes, including stillbirth, when BA > 100 µmol/L. Methods: This retrospective study, conducted at a tertiary perinatology centre between 2019 and 2023, was performed in two phases. In the first phase, baseline group characteristics and pregnancy outcomes were compared between ICP and non-ICP (control) groups. In the second phase, outcomes were analysed across three ICP severity subgroups: mild (BA < 40 µmol/L), moderate (BA 40–99 µmol/L), and severe (BA ≥ 100 µmol/L). Results: A total of 210 patients diagnosed with ICP and 24,177 controls were included in the analysis. After multivariable regression, the results indicated that patients with severe ICP (BA ≥ 100 µmol/L) experienced significantly worse perinatal outcomes compared to those with mild or moderate disease: spontaneous preterm birth occurred in 26.7% of cases (p = 0.002), iatrogenic preterm birth in 36.7% (p < 0.001), meconium-stained amniotic fluid in 43.3% (p = 0.001), and neonatal intensive care unit (NICU) admission in 23.3% (p = 0.006). This subgroup also had the lowest mean birth weight (2830 g, p < 0.001). Notably, no stillbirths were recorded in any of the subgroups. Compared to controls, no major differences in maternal characteristics were noted, except in pregnancies conceived via in vitro fertilisation (IVF, p = 0.012) and those complicated by gestational diabetes (p = 0.040), both showing elevated risk for ICP development. Conclusions: This study confirms an association between ICP and increased perinatal complications, with severity of disease correlating with poorer outcomes. The findings highlight the need for standardised BA testing and improved strategies for perinatal management. Full article

Gestational diabetes mellitus (GDM) is a growing global health concern, driving the need for novel diagnostic and prognostic approaches. The aim of this study was to analyze the amino acid profile in the mother–fetus system (maternal venous blood, umbilical cord blood, and amniotic fluid) and to identify specific biological markers of GDM and macrosomia. Using HPLC-MS/MS, we analyzed serum from maternal venous and umbilical cord blood, along with amniotic fluid, across 94 mother–fetus pairs (53 GDM, 41 controls). Machine learning and metabolic pathway analysis revealed significant alterations in 19 amino acids. In GDM, maternal serum showed elevated 5-OH-lysine and homocitrulline, while cord blood had higher isoleucine, serine, and threonine. Amniotic fluid exhibited increased leucine, isoleucine, threonine, serine, arginine, and ornithine. Conversely, histidine, glutamine, alanine, asparagine, β-/γ-aminobutyric acids, phenylalanine, ornithine, and citrulline were reduced. Histidine, glutamine, and asparagine inversely correlated with blood glucose (r = −0.26, r = −0.33, r = −0.30) and were lower in GDM. These findings highlight three key metabolic loci in GDM pathogenesis, with glutamine, histidine, and asparagine emerging as potential maternal blood biomarkers for early macrosomia prediction. However, given confounding factors in metabolomic studies, further large-scale validation is essential. Full article

Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent hepatobiliary disorder unique to gestation, characterized by maternal pruritus and elevated serum bile acids. While maternal prognosis is favorable, mounting evidence links ICP to a range of neonatal complications. This narrative review aims to synthesize the current knowledge on the pathophysiological mechanisms, clinical impact and management strategies related to neonatal outcomes in ICP. Methods: A narrative review approach was employed, drawing on recent clinical guidelines, observational studies, mechanistic investigations and meta-analyses. Emphasis was placed on evidence exploring the relationship between maternal bile acid concentrations and neonatal morbidity, as well as on established and emerging therapeutic interventions. No systematic search strategy or formal quality appraisal was undertaken. Results: ICP is associated with an increased risk of adverse neonatal outcomes, including spontaneous and iatrogenic preterm birth, meconium-stained amniotic fluid, respiratory distress syndrome and stillbirth, particularly when bile acid concentrations exceed 100 μmol/L. Proposed mechanisms include placental vasoconstriction, arrhythmogenic effects and surfactant inhibition. Ursodeoxycholic acid remains the most widely used pharmacologic agent for maternal symptom relief, although evidence supporting neonatal benefit is inconclusive. Delivery by 36–37 weeks is generally recommended in cases of severe cholestasis to mitigate fetal risk. Conclusions: Severe ICP confers substantial neonatal risk, requiring individualized, bile-acid-guided management. While current therapies offer symptomatic maternal benefit, optimization of fetal outcomes requires timely diagnosis, vigilant surveillance and evidence-based delivery planning. Further research is warranted to refine therapeutic targets and standardize clinical practice. Full article

Preterm labour (PTL) affects about 11% of all deliveries world-wide. It is a major cause of perinatal morbidity and mortality. Although the precise cause is unknown in about 50% of cases, infections are thought to be a major contributing factor. These infections are more common in earlier preterm deliveries. While some women with these infections will manifest the classical features of fever, tachycardia (maternal and/or fetal), leucocytosis, raised biomarkers of infections, and uterine tenderness/irritation, others will be asymptomatic. Some of the women may develop a short/dilating cervix without any obvious contractions. Identifying such women is potentially challenging. Evidence has shown that a condensation of echogenic particles just above the cervix—amniotic fluid (AF) sludge, identified by ultrasound—is a marker for microbial invasion of the amniotic cavity (MIAC) and preterm birth (PTB) in both asymptomatic and symptomatic women (including those with a short or normal cervix). Those with a short cervix with AF sludge have a significantly greater risk of progression to PTB. Treatment with antibiotics has been shown in some but not all case series to result in a resolution of the sludge and either a delay or prevention of PTB. The widely varied results from treatment could be related to the antibiotics used and the route of administration. The use of the parenteral combination of clindamycin, a cephalosporin, and metronidazole has been shown to be more effective compared to azithromycin. Here we review the literature on the relationship between the sludge and PTB and conclude (1) that the AF sludge is an ultrasound marker of MIAC and PTL and (2) that following its diagnosis, appropriate counselling should be offered and the triple antibiotic combination offered. We suggest that randomised trials should be undertaken to determine the most efficacious antibiotic combination. Full article

Introduction: Amniotic fluid (AF) plays a pivotal role in foetal gastrointestinal development by delivering bioactive factors that support intestinal maturation. However, the redox environment of AF and its potential contribution to foetal intestinal homeostasis remain insufficiently characterised. This study aimed to quantify key antioxidant markers—superoxide dismutase isoforms (SOD1, SOD3), glutathione (GSH), and the oxidative DNA damage marker 8-hydroxy-2-deoxyguanosine (8-OHdG)—in AF across gestational ages and compare them with those in human milk (HM). Methods: AF samples (n = 60) were collected from pregnancies between 15 and 40 weeks of gestation, grouped into preterm (<37 weeks) and term (≥37 weeks). SOD1, SOD3, GSH, and 8-OHdG concentrations were quantified using ELISA. HM samples (n = 45) were similarly analysed. Results: SOD1 and SOD3 in AF concentrations decreased significantly with gestational age (GA) (p < 0.001), while 8-OHdG levels increased (p < 0.001). SOD3 showed a negative correlation with 8-OHdG (p = 0.004). HM contained significantly higher levels of both SOD isoforms compared to AF (AF vs. HM: 35.6 (1.9–172.3) vs. 267.9 (54.6–843.8), p < 0.001 for SOD1 and 1.2 ng/mL (0.1–26.5) vs. 5.5 ng/mL (0.1–300.0), p < 0.001 for SOD3), regardless of GA. Conclusions: Our findings highlight the dynamic nature of the redox environment in AF and its potential importance for foetal GIT development. The disruption of redox balance by preterm birth or inadequate AF intake during foetal life may have long-term consequences for intestinal development and function. These insights provide a foundation for future clinical studies aimed at enhancing neonatal feeding regimens, particularly for preterm infants and those with congenital gastrointestinal disorders. Full article

Osteosarcopenia is a widespread geriatric condition resulting from the coexistence of osteoporosis and sarcopenia, where the connection between bone and muscle is, in part, driven by bone–muscle crosstalk. Given the close, reciprocal influence of muscle on nerve, and vice versa, it is not surprising that there are corresponding aging changes in the biochemistry and morphology of the neuromuscular junction (NMJ). Indeed, degeneration of motor neurons and progressive disruption of the neuromuscular connectivity were observed in old age. Extracellular vesicles (EVs) derived from human amniotic fluid stem cells (hAFSC), exhibiting antioxidant properties, which can also explain their anti-aging and cytoprotective effects, can be considered as potential treatment for age-related diseases. To study cell interactions under both healthy and pathological conditions occurring in musculo–skeletal apparatus, we developed a three-culture system exploiting the use of well-known transwell supports. This system allows both myotubes and neurons, eventually treated with EVs, and osteoblasts, induced to osteoporosis, to interact physically and biochemically. Collectively, this method allowed us to understand how the modifications induced in osteoblasts during bone disorders trigger a cascade of detrimental effects in the muscle and neuron parts. Moreover, we demonstrated the efficacy of hAFSC-EVs in preventing NMJ dysfunction, muscle atrophy, and osteoblast impairment. Full article