Search Results (1,660)

Background/Objectives: Accurate identification of neonatal malnutrition is essential for optimizing perinatal care and reducing adverse outcomes. Traditional birthweight-based methods fail to account for body proportionality, limiting their ability to distinguish constitutionally small or large neonates from those with true nutritional abnormalities. We previously developed a customized fetal body mass index (cFBMI) percentile model that incorporates both weight and length, adjusted for maternal and fetal characteristics. This study aims to perform a temporal external validation of the cFBMI model following the Riley et al. framework, comparing its performance against the GROW customized birthweight model and the INTERGROWTH-21st population-based standard. Methods: A temporal validation study was conducted using singleton deliveries from Hospital Universitario de Puerto Real, Cádiz, Spain. The development cohort comprised 7864 deliveries (2002–2021); the validation cohort comprised 4441 deliveries (2022–2025). Inclusion criteria: singleton pregnancy, gestational age of 33–42 + 6 weeks, birthweight of 500–6000 g, known neonatal sex and length, and complete maternal data. The Ponderal Index (PI = weight/length³ × 100) stratified by sex and gestational age served as the gold standard (undernutrition: PI < p10; overnutrition: PI > p90). Discrimination was assessed using the area under the receiver operating characteristic curve (AUC) with bootstrap 95% confidence intervals (2000 iterations) and DeLong tests. Calibration was evaluated by comparing observed versus expected proportions across percentile categories. Clinical utility was assessed using decision curve analysis (DCA). Temporal stability was quantified by comparing AUCs and Brier scores between the development and validation cohorts. Results: In the validation cohort (n = 4441), cFBMI demonstrated superior discrimination for both undernutrition (AUC: 0.962) and overnutrition (AUC: 0.961) compared with GROW (AUC: 0.751 and 0.676, respectively) and INTERGROWTH-21st (AUC: 0.756 and 0.682, respectively); all DeLong comparisons p < 0.0001. The cFBMI exhibited excellent temporal stability (ΔAUC = −0.004 for undernutrition, +0.002 for overnutrition) and superior calibration (observed proportions: 9.6%/81.7%/8.8% vs. expected 10%/80%/10%; χ² = 9.22, p = 0.010). The decision curve analysis confirmed the superior net benefit of cFBMI across all threshold probabilities. Conclusions: The customized fetal BMI percentile model demonstrates excellent and temporally stable discriminative performance in this single-institution temporal validation study, with superior calibration and apparent advantages in clinical utility as determined by decision curve analysis compared with existing methods. Its integration of body proportionality provides conceptual alignment with the Ponderal Index gold standard. These findings are promising but require confirmation through external multicenter validation before clinical implementation can be recommended. Although the mathematical relationship between the index test (weight/length²) and the reference standard (weight/length³) should be considered when interpreting the magnitude of discrimination metrics, validation against independent clinical outcomes is an essential next step. The cFBMI thus provides a proportionality-aware nutritional metric whose primary discriminative advantage over weight-based methods is realized at and beyond the moment of birth, and which is forward-compatible with emerging modalities for independent prenatal fetal length estimation. 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

The isolation of fibroblast-like cells from crocodile skeletal muscle provides a valuable platform for studies in comparative physiology, reptilian biology, regenerative medicine, and tissue engineering. In this article, we present an optimized protocol for isolating and characterizing fibroblast-like cells derived from the embryonic skeletal muscle of the Siamese crocodile (Crocodylus siamensis). The procedure improved cell yields and viability while maintaining phenotypic and genetic stability. Dorsal and tail skeletal muscle tissue was cultured in flasks pre-coated with collagen. The cells attached and began migrating from the explants within one day. Optimal culture conditions were achieved using Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12 or Minimum Essential Medium Alpha supplemented with 10% fetal bovine serum, 2% crocodile serum, and growth-promoting factors, incubated at 28 °C without CO₂. These conditions supported a shorter population doubling time and enhanced cell proliferation. The established cells displayed a spindle-shaped fibroblastic morphology, expressed the fibroblast-specific marker fibronectin, and maintained a stable karyotype through passage 20. The cell line remained stable and proliferative for at least 30 passages under standard culture conditions. Our study established the first standardized fibroblast-like cell line derived from C. siamensis, thus providing a foundation for future studies in reptilian physiology, cytogenetics, and regenerative biotechnology. 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

Electronic waste (e-waste) recycling releases heavy metals into surrounding environments, creating potential health risks for nearby populations, particularly pregnant women and developing fetuses. This systematic review evaluated human evidence linking prenatal exposure to heavy metals originating from informal e-waste recycling with adverse pregnancy and neonatal outcomes. Electronic databases, including PubMed and Scopus, were searched through 23 September 2025, for studies measuring heavy metal exposure among pregnant women or neonates living in e-waste–affected communities. Following the Navigation Guide methodology, eight observational studies met the inclusion criteria and were assessed for risk of bias and strength of evidence. Across studies, concentrations of heavy metals were higher in exposed populations and were detected in maternal blood, placenta, cord blood, urine, and meconium samples from exposed populations. Prenatal exposure was consistently associated with adverse outcomes, with many studies reporting statistically significant associations between heavy metal exposure and reduced birth weight, length, head circumference, gestational age, neonatal body mass index, lower Apgar scores, impaired neonatal neurobehavioral development, placental molecular alterations, endocrine disruption, and increased neonatal DNA damage. Overall, the evidence was rated as moderate quality with sufficient evidence linking prenatal heavy-metal exposure from e-waste to impaired fetal growth and neonatal development, and limited evidence for pregnancy complications. These findings highlight the need for improved regulation of e-waste recycling and strengthened public health protections for vulnerable populations. 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

Maternal consumption of alcohol and drugs during pregnancy can compromise neural development with long-lasting impact on individuals’ health. The inhibitor of growth (ING) family of proteins is an epigenetic regulator that plays a central role in fetal brain development, contributing to neural stem cell maintenance, neuronal differentiation, and the regulation of genes involved in brain morphogenesis. Given the susceptibility of the developing nervous system to epigenetic dysregulation induced by alcohol and drugs, this narrative study aims to summarize literature evidence with the hypothesis that ING proteins may represent a critical but understudied mechanistic link between maternal substance dependence and adverse neurodevelopmental outcomes in newborns. We conducted a comprehensive literature search across three databases (PubMed, Scopus, and Web of Science) up to February 2026 to identify relevant studies. Search terms included combinations of “ING proteins”, “neural development”, “alcohol”, “drugs”, “epigenetic”, “oxidative stress” and “neuroinflammation”. The inclusion criteria were limited to original studies published in English that examined neural development in newborns; the exclusion criteria encompassed non-English publications, letters, editorials, and case reports, and those not directly addressing the specified topics. We identified 55 papers; six were excluded per the exclusion criteria, leaving 49 works discussed in this review. ING proteins are epigenetic regulators essential for embryonic and neural development, including neural stem cell fate and neurogenesis, while substances of abuse are disruptors of the essential pathways necessary for the right fetal brain development. Furthermore, substance abuse creates oxidative stress environments and activates pathways that require ING-mediated chromatin regulation. ING proteins likely act as mediators linking oxidative stress, neuroinflammation, and transcriptional reprogramming in the developing brain. Meanwhile, alcohol and drugs induce epigenetic reprogramming that may disrupt ING-mediated chromatin control. There is little evidence directly linking prenatal exposure (e.g., alcohol and drugs) to ING changes during fetal development. However, we hypothesize that ING proteins function as epigenetic stress response regulators whose disruption by oxidative stress, inflammation, and chromatin alterations induced by prenatal alcohol or drug exposure may contribute to impaired fetal neurodevelopment. Although direct experimental evidence remains limited, this could be a promising and relatively unexplored research area. 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

Congenital diaphragmatic hernia (CDH) is a severe developmental defect characterized by pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Fetoscopic endoluminal tracheal occlusion (FETO) is a prenatal intervention used in severe CDH to stimulate lung growth, yet its effects on fetal cardiac function remain insufficiently understood. This systematic review aimed to evaluate the impact of FETO on cardiac structure and function in fetuses with CDH. A comprehensive literature search identified four studies that met the inclusion criteria. Most studies were retrospective and showed considerable heterogeneity in study design. Overall, the available evidence suggests that FETO does not negatively affect fetal cardiac function and may promote favorable cardiac remodeling. Several studies reported improved growth of left-sided cardiac structures and better right ventricular performance in FETO-treated fetuses compared with severity-matched controls. Given the limited number of studies and their methodological variability, these findings should be interpreted with caution. Further well-designed, prospective studies with standardized cardiac assessment protocols and clearly defined outcome measures are needed to better characterize the cardiovascular effects of FETO in CDH. Full article

This prospective study evaluated first-trimester markers in pregnancies with isolated and combined forms of fetal growth disorders and gestational diabetes mellitus (GDM). Among 1869 screened women, the analysis included 83 controls, 55 GDM, 22 isolated intrauterine growth restriction (iIUGR), and 33 isolated large-for-gestational-age (iLGA) cases, with GDM subgroups stratified by fetal growth (GDM with normal fetal weight, GDM + IUGR, and GDM + LGA). First-trimester clinical and routine biochemical parameters were recorded, and serum concentrations of 80 proteins were measured using targeted LC-MRM-MS proteomics. Different trajectories emerged: IUGR phenotypes showed low PAPP-A/PlGF and high TSH (p < 0.01), indicating early placental insufficiency, while macrosomia showed opposite trends. GDM + IUGR represented the most severe “double hit” phenotype (lowest PlGF, earliest delivery), whereas GDM + LGA showed increased umbilical artery resistance despite excessive growth, suggesting endothelial dysfunction. Targeted proteomics revealed characteristic signatures: iIUGR featured low complement (C4A|C4B) and IGF proteins (IGFALS, IGFBP3) versus GDM and iLGA (p < 0.001); GDM + IUGR showed elevated PZP and CD5L versus iIUGR (p < 0.05); GDM + LGA was marked by high C4BPA and low RBP4, SERPINA7 versus iLGA (p < 0.05). Complement and IGF pathways were consistently implicated. Machine learning achieved 77% sensitivity for IUGR prediction using clinical parameters and 88% sensitivity for LGA prediction using proteomic data. These findings demonstrate that fetal growth disorders represent pathophysiologically unique entities detectable in the first trimester, enabling early risk stratification and personalized management. Full article

Objective: This study aimed to describe gestational age-specific biometric and estimated fetal weight (EFW) patterns derived from a multicenter cohort of fetuses with gastroschisis and to evaluate the agreement between prenatal EFW and birth weight. Methods: This retrospective study included singleton pregnancies with a prenatal diagnosis of gastroschisis and at least two ultrasound evaluations between 20 and 37 weeks. Data were collected from four Brazilian tertiary centers between 2010 and 2024. Biometric parameters (biparietal diameter, head circumference [HC], abdominal circumference, and femur length) and EFW were recorded. EFW was calculated using Hadlock IV and Siemer formulas. Polynomial regression models were applied to generate gestational age-specific curves for HC, femur length (FL), and EFW. Agreement between prenatal EFW and birth weight (in cases assessed within 14 days of delivery) was analyzed using Bland–Altman plots and the concordance correlation coefficient (CCC). Results: A total of 116 pregnancies and 355 ultrasound tests were included. Polynomial models showed a strong association between gestational age and EFW (R² = 0.837 for Siemer; R² = 0.728 for Hadlock), HC (R² = 0.849), and FL (R² = 0.877). The 50th percentile curves for gastroschisis were consistently lower than those from standard growth charts. In the birthweight concordance analysis (n = 46), the Siemer formula showed low agreement (CCC = 0.55), while the Hadlock formula showed even lower concordance (CCC = 0.44), with both formulas underestimating actual birth weight. Conclusions: Fetuses with gastroschisis have distinct growth patterns not captured by standard references. Tailored growth curves and careful interpretation of EFW are essential to improve prenatal assessment in this population. Full article

The Barker hypothesis links intrauterine conditions, mainly low birth weight, subject to poor nutrition with paradoxically improved standards of living and nutrition after World War II in Western countries, to adult disease, mainly coronary heart disease. The limitations of his hypothesis include the fact that it is based only on human epidemiological data and animal studies, and also that it is difficult to isolate the effect of the intrauterine environment from postnatal conditions, familial and genetic background. In the last 20 years, the introduction of ultrasound and Doppler techniques in the assessment of fetal and maternal vascularity added a major contribution to the evaluation of the intrauterine environment. Studies based on ultrasound and Doppler assist in differentiating between prematurity and fetal growth restriction (FGR), mainly in those with placental insufficiency, and postnatal morbidity and even mortality. In addition, the Pedersen hypothesis regarding fetuses with overgrowth, mainly with diabetic mothers, states that they are also prone to postnatal morbidity. However, most of the studies on the issue do not emphasize the effects of the intrauterine environment on fetal organs, such as the brain, heart, liver, kidneys and pancreas in FGR and fetal overgrowth, that may impose a different prognosis in later life. This narrative review aims to summarize current evidence from animal and human studies regarding the impact of intrauterine undernutrition and overnutrition on fetal organ development, and to evaluate how ultrasound and Doppler findings may contribute to understanding the link between the intrauterine environment and postnatal morbidity. Full article

Background: Experimental studies indicated that maternal choline and betaine status have the potential to alter fetal growth, but epidemiological data remain sparse. Objective: We aimed to investigate the association of maternal and cord blood choline and betaine concentrations with birthweight outcomes. Methods: This prospective cohort study involved 988 mother–infant dyads from Hebei and Shandong provinces. Plasma concentrations of choline and betaine in maternal late pregnancy and cord blood were quantified using ultra-performance liquid chromatography–mass spectrometry. Multivariable linear or logistic regression was performed to examine their association with continuous or binary birthweight outcomes. Results: Maternal plasma choline and betaine concentrations in late pregnancy (median [interquartile range]; 12.34 [10.13, 14.78] and 14.99 [12.01, 18.36] μmol/L) were significantly lower than those in cord blood (29.98 [24.74, 35.93] and 31.14 [25.56, 37.28] μmol/L). Each 1 μmol/L increase of late-pregnancy and cord blood betaine concentrations were associated with 9.87 g (95% confidence interval [CI]: −16.08, −3.66 g) and 5.29 g (95% CI: −8.52, −2.06 g) lower birthweight, respectively. Compared with the lowest quintile, the highest quintiles of late-pregnancy and cord blood betaine concentrations were associated with lower risks of large-for-gestational-age (adjusted odds ratios [ORs] = 0.47 [95% CI: 0.24, 0.90] and 0.31 [95% CI: 0.17, 0.56]) and macrosomia (adjusted ORs = 0.12 [95% CI: 0.03, 0.43] and 0.15 [95% CI: 0.05, 0.40]). These associations, particularly for cord blood, persisted and appeared more pronounced in pregnancies with maternal overweight/obesity or gestational diabetes mellitus (GDM), but the interaction effect did not reach statistical significance. No significant associations were observed for choline in any periods. Conclusions: Higher plasma concentrations of betaine in maternal late-pregnancy and cord blood were associated with lower birthweight. These findings emphasize the importance of sufficient betaine status during pregnancy, especially among mothers with obesity or GDM. Full article