Search Results (414)

This review aimed to be comprehensive and to critically analyze the factors that may affect the macronutrient and energy content of breast milk. Systematic reviews were prioritized, even though other types of literature reviews on the subject, as well as studies not included in these reviews, were included. Reported factors that potentially affect the macronutrient and energy content of breast milk comprise: maternal factors, such as age, nutritional status, dietary intake, smoking habits, lactation stage, circadian rhythmicity, and the use of galactagogues; obstetrical factors, such as parity, preterm delivery, multiple pregnancies, labor and delivery, and pregnancy morbidities including intrauterine growth restriction, hypertensive disorders, and gestational diabetes mellitus; and newborn factors, including sexual dimorphism, and anthropometry at birth. Some factors underwent a less robust assessment, while others underwent a more in-depth analysis. For example, the milk from overweight and obese mothers has been reported to be richer in energy and fat. A progressive decrease in protein content and an increase in fat content was described over time during lactation. The milk from mothers with hypertensive disorders may have a higher protein content. Higher protein and energy content has been found in early milk from mothers who delivered prematurely. Full article

Background/Objectives: Overt hypothyroidism during pregnancy has been linked to adverse outcomes, including preterm birth, low birth weight, and impaired fetal neurocognitive development. This study aimed to evaluate pregnancy complications in women with overt hypothyroidism (TSH ≥ 10) through a cross-sectional study. Methods: Data from 259,897 live-birth pregnancies (2013–2022) from Clalit Health Services (CHS) were analyzed. The study included all CHS-insured women aged ≥ 18 years with available TSH results during pregnancy. Overt hypothyroidism was defined as a mean TSH ≥ 10 mIU/L, while the euthyroid reference group had TSH levels < 4 mIU/L and no history of hypothyroidism or levothyroxine use. Cases of overt hypothyroidism were matched with 15 controls using propensity score-based matching. Covariates included maternal age, ethnicity, socioeconomic status, IVF use, recurrent pregnancy loss, and smoking. Pregnancy complications were compared between groups using descriptive statistics and univariate analysis. A quasi-Poisson regression model was used to assess complication risk in overt hypothyroidism versus matched controls. Results: The final analysis included 9125 euthyroid and 611 overt hypothyroid pregnancies, with comparable baseline characteristics between groups. No significant differences were found in maternal age, ethnicity, socioeconomic scores, IVF rates, recurrent pregnancy loss, diabetes, smoking, gestational age at delivery, or rates of preterm birth, pre-eclampsia, gestational diabetes, cesarean section, and intrauterine growth restriction. Overall, overt hypothyroidism was not associated with increased complications. Sensitivity analyses using maximum TSH levels during pregnancy showed a slightly elevated risk for pregnancy complications (IRR 1.1, CI 1.04–1.18; p = 0.002). Conclusions: Overt hypothyroidism was not associated with an increased risk of adverse pregnancy outcomes when adjusted for confounding factors, suggesting that treatment decisions should be made on an individual basis. Full article

Intrauterine growth restriction (IUGR) is a critical challenge in perinatal medicine and is associated with significant morbidity and mortality. This review explores the intricate involvement of early developmental senescence in IUGR. We highlight the dual role of cellular senescence in both normal development and pathological conditions, emphasizing the need for further research to elucidate these mechanisms and develop targeted interventions. We discuss how oxidative stress and mitochondrial dysfunction affect senescence determinants. We present emerging therapeutic strategies aimed at targeting senescence and inflammation in the placenta. We also introduce Rytvela, an interleukin-1 (IL-1) receptor modulator developed in our laboratory, which selectively attenuates pro-inflammatory signaling while preserving essential immune responses, which in turn mitigate senescence. By addressing senescence-related dysfunctions, such interventions may improve placental performance and fetal outcomes, opening up new directions for the clinical management of IUGR. Full article

Antenatal corticosteroids are widely used to prevent newborn morbidity and mortality in special obstetric circumstances, especially in preterm birth, but there are ongoing concerns about possible neutral or even detrimental short- and long-term effects in pregnancies complicated by fetal growth restriction. Fetuses with growth restriction may be a subset of preterm infants with a particular vulnerability to steroid exposure. The current scientific evidence on exogenous antenatal corticosteroid effects in this population is not conclusive. Gestational age (early versus late) is a critical issue to assess regarding their use as standard care in this special obstetric circumstance. Full article

Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential for extravillous trophoblast cell viability, motility, and invasion. Genome-scale transcriptomics identified an SRC-2-dependent transcriptome in HTR-8/SVneo cells that encodes a diverse spectrum of proteins involved in placental tissue development and function. Underscoring the utility of this transcriptomic dataset, we demonstrate that WNT family member 9A (WNT 9A) is not only regulated by SRC-2 but is also crucial for maintaining many of the above SRC-2-dependent cellular functions of human extravillous trophoblasts. Full article

Background/Objectives: Intrauterine growth restriction (IUGR) is a pathological condition defined by a reduced fetal ability to achieve the genetically expected growth potential during gestation. It affects 5–10% of all pregnancies and it is a leading cause of perinatal morbidity and mortality. During the initial phases of placentation, complex interlinked processes including cell proliferation, differentiation, apoptosis and the invasion of trophoblasts occur. Alterations in the regulation of these processes lead to placental dysfunction. Survivin, a member of the inhibitor of apoptosis (IAP) family, plays an important role in cell proliferation balance and apoptosis, thus leading to proper placental development. This study aimed to evaluate survivin expression in placentas from IUGR and healthy pregnancies to explore its potential as a biomarker for the early diagnosis, prevention, and treatment of IUGR. Methods: Survivin presence was determined in 153 archival formalin-fixed and paraffin-embedded placental tissues from IUGR (N = 122) and uncomplicated (N = 31) term pregnancies. Tissue microarrays (TMAs) were constructed, and survivin expression was assessed using immunohistochemistry (IHC). Survivin levels were quantified using positive cell proportion (PCP) scores and immunoreactive scores (IRS), with statistical significance determined using mean values, standard deviation (SD), standard error, and Student’s t test in instances of normal distribution, and when this was not the case, the Mann–Whitney test. Chi-square tests, Fisher exact tests, and t-tests (p < 0.05) were used to compare categorical variables. Results: Our results suggested the significantly higher expression of survivin validated with PCP (p < 0.001) and IRS (p < 0.002) in placentas with IUGR compared to placentas from non-complicated term pregnancies. Conclusions: Increased survivin expression in IUGR placentas points to its potential role as a key indicator of placental dysfunction. By signaling early pathological changes, survivin may offer a valuable tool for the early detection of IUGR, potentially allowing for timely clinical interventions that could reduce the risk of serious outcomes, including stillbirth. To fully establish survivin’s clinical value, further research is needed to validate its diagnostic accuracy and to explore its involvement in molecular pathways that may be targeted for therapeutic benefit. Full article

Background: The Fibroblast Growth Factor (FGF) 19 subfamily plays a key role in the regulation of metabolic and growth processes, and their dysregulation can lead to fetal growth disorders, such as small for gestational age (SGA) and large for gestational age (LGA), as well as to pathogenesis and development of gestational diabetes and gestational hypertension. Methods: We conducted a narrative review using the PRISMA2020 statement. Two electronic databases were searched: PubMed and Web of Science until October 2024. The search terms were as follows: (FGF-21 OR fibroblast growth factor-21 OR FGF-23 OR fibroblast growth factor-23 OR FGF-19 OR fibroblast growth factor-19) AND (human fetus development OR fetal growth OR infancy). We only included original papers that analysed the effect of FGF-19,21,23 on pre- and postnatal development. Results: Only 6 out of 203 studies met the inclusion criteria. There were higher concentrations of FGF-21 among patients with gestational diabetes mellitus (GDM) compared to healthy females, but no differences were found in FGF-21 values in newborn’s umbilical cord blood. Interestingly, higher FGF-21 concentrations were observed in females than males born to patients with GDM. FGF-19 was linked to fetal development by its association with chronic insulin secretion levels during fetal life, particularly in female newborns, but no significant correlation with GDM was found. The evaluation of the role of FGF-23 has shown that its low level could be related to gestational hypertension and fetal growth restriction. Conclusions: In conclusion, all the studies discussed suggest that FGF-19 subfamily factors may play an important role in fetal and neonatal growth and development, particularly in pregnancies complicated by metabolic disorders, such as gestational diabetes or gestational hypertension. Differences in FGF-19 and FGF-21 concentrations based on gender and gestational disorders suggest the need for further research in order to fully understand the effects of these proteins and their potential clinical applications. Full article

Glycine has the greatest rate of deposition in whole-body proteins among all amino acids in neonates, but its provision from sow’s milk meets only 20% of the requirement of suckling piglets. The results of our recent studies indicate that piglets with intrauterine growth restriction (IUGR) have a reduced ability to synthesize glycine. The present study determined the role of glycine in the growth of sow-reared IUGR piglets. In Experiment 1, 56 newborn piglets (postnatal day 0) with a low birth weight (<1.10 kg) were selected from 14 litters, providing 4 IUGR piglets/litter that were allotted randomly into one of four treatment groups (14 piglets/group). Piglets received oral administration of either 0, 0.1, 0.2 or 0.4 g glycine/kg body weight (BW) twice daily (i.e., 0, 0.2, 0.4 or 0.8 g glycine/kg BW/day) between 0 and 14 days of age. L-Alanine was used as the isonitrogenous control. The BWs of all piglets were recorded each week during the experiment. Two weeks after the initiation of glycine supplementation, blood and tissue samples were collected for biochemical analyses. In Experiment 2, rates of muscle protein synthesis in tissues were determined on day 14 using the ³H-phenylalanine flooding dose technique. Compared with piglets in the control group, oral administration of 0.2, 0.4 and 0.8 g glycine/kg BW/day did not affect their milk intake (p > 0.05) but increased (p < 0.05) concentrations of glycine in plasma by 1.52-, 1.94-, and 2.34-fold, respectively, and body weight by 20%, 37%, and 34%, respectively. The dose of 0.4 g glycine/kg BW/day was the most cost-effective. Consistent with its growth-promoting effect, glycine supplementation stimulated (p < 0.05) the phosphorylation of mechanistic target of rapamycin (MTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and ribosomal protein S6 kinase beta-1 (p70^S6K) as well as protein synthesis in skeletal muscle, compared with the control group. Collectively, oral administration of glycine activated the MTOR signaling pathway in skeletal muscle and enhanced the growth performance of IUGR piglets. These results indicate that endogenous synthesis of glycine is inadequate to meet the needs of IUGR piglets during the suckling period and that oral supplementation with glycine to these compromized neonates can improve their growth performance. Full article

Background/Objectives: Fetal thigh circumference (ThC) may be a valuable parameter for assessing fetal growth. Thus, this study aimed to establish reference ranges for ThC across gestational ages (GA). Methods: This retrospective study included singleton pregnancies between 12 and 38 weeks of gestation. ThC measurements were obtained during routine ultrasound examinations. GA was confirmed through the last menstrual period and first-trimester crown–rump length measurements. Percentile ranges for ThC were calculated for each gestational week, and statistical analyses evaluated the relationship between ThC and GA. Results: 48,841 singleton pregnancies were included. A positive correlation was observed between ThC and GA, with ThC values increasing progressively from 12 to 38 weeks. The study established the 10th, 50th, and 90th percentile ranges for ThC, providing reference values for clinical assessments. Conclusions: This study provides reference ranges for fetal ThC across a wide GA range, highlighting its potential as a tool in prenatal care. ThC may offer an additional parameter for monitoring fetal growth, especially when standard measurements are challenging. Further research should investigate the integration of ThC with other fetal growth parameters to enhance its clinical utility. Additionally, these nomograms can be used to assess their usefulness in certain conditions, such as intrauterine growth restriction (IUGR), macrosomia, and congenital skeletal dysplasias. Full article

Infective endocarditis (IE) during pregnancy, while uncommon, is associated with substantial maternal and fetal morbidity and mortality due to the complex physiological adaptations of pregnancy. Hemodynamic alterations, including increased cardiac output and changes in vascular resistance, combined with immunological modulation, predispose pregnant individuals to increased risk of infection and associated complications. Predominant pathogens implicated in pregnancy-associated IE are Staphylococcus aureus, Streptococcus viridans, and Enterococcus faecalis, with S. aureus infections frequently leading to poorer clinical outcomes. Diagnosis remains challenging due to commonly atypical presentation and relies on microbiological identification via blood cultures in conjunction with imaging modalities such as transthoracic echocardiography. IE in pregnancy is associated with increased maternal mortality rates (5–17%) and adverse fetal outcomes, including preterm birth, intrauterine growth restriction (IUGR), and fetal loss. Management necessitates careful selection of antimicrobial therapy to ensure efficacy while minimizing fetal toxicity, especially in settings of increased antimicrobial resistance. Anticoagulation and surgical interventions must be judiciously considered, with surgical timing individualized based on the severity of heart failure and coordinated multidisciplinary care. In conclusion, IE during pregnancy constitutes a significant clinical challenge, underscoring the need for enhanced diagnostic strategies, optimized therapeutic protocols, and the development of pregnancy-specific management guidelines to improve maternal and fetal outcomes. Full article

Background: Mitochondria are essential for placental function as they regulate energy metabolism, oxidative balance, and apoptotic signaling. Increasing evidence suggests that placental mitochondrial dysfunction may play a role in the development of many poor perinatal outcomes, including preeclampsia, intrauterine growth restriction (IUGR), premature birth, and stillbirth. Nonetheless, no systematic review has thoroughly investigated this connection across human research. This study aims to consolidate evidence from human research concerning the link between placental mitochondrial dysfunction and negative birth outcomes. Methods: A systematic search of PubMed, Scopus, and Web of Science identified human research examining placental mitochondrial features (e.g., mtDNA copy number, ATP production, oxidative stress indicators) in connection with adverse pregnancy outcomes. Methodological variety resulted in narrative data extraction and synthesis. Results: Twenty-nine studies met the inclusion criteria. Mitochondrial dysfunction was consistently associated with PE, IUGR, FGR, and PTB. The most often observed outcomes included diminished mtDNA copy number, decreased ATP production, elevated reactive oxygen species (ROS), and disrupted mitochondrial dynamics, characterized by increased DRP1 and decreased MFN2. Early-onset preeclampsia and symmetric fetal growth restriction exhibited particularly severe mitochondrial abnormalities, indicating a primary placental origin of the condition. Conclusions: A significant factor contributing to adverse pregnancy outcomes is the dysfunction of placental mitochondria. The analogous molecular signatures across many disorders suggest promising avenues for developing targeted therapies aimed at improving maternal–fetal health and predictive biomarkers. Full article

Congenital malformations constitute a major public health issue. Nonetheless, Greece does not participate in the European network of congenital anomalies. To examine the epidemiology of congenital abnormalities and investigate possible factors associated with their development, autopsies were performed on 649 fetuses referred from three healthcare facilities in Thessaloniki during 1992–2008. Adequate statistical analysis methods were implemented. Birth defects were found in 256 fetuses (39.5%)—primarily related to the musculoskeletal (17.3%), nervous (14.5%), cardiovascular (12.5%) and urinary (10.4%) systems. A statistically significant positive correlation (p-values < 0.05) emerged between the presence of a congenital defect and intrauterine growth restriction, inability to identify the fetus’ sex, iatrogenic abortion, nuchal oedema and a single umbilical artery. An inverse association (p-values < 0.05) was deduced with the gestational age, twin pregnancy, stillbirth, chorioamnionitis, infarction and intervillous thrombus of the placenta and nuchal cord. In multivariable analysis, the relationship remained significant (p-values < 0.05) between the development of birth defects and iatrogenic abortion, nuchal oedema, presence of a single umbilical artery, chorioamnionitis, infarction of the placenta and nuchal cord. ROC curve analysis indicated area under the curve = 0.800, 95% confidence interval = 0.76–0.84, p-value = 0.000. Our study revealed the epidemiology of congenital anomalies in Greece, confirming the relationship between various factors and birth defect occurrence. Full article

Background/Objectives: Intrauterine growth restriction (IUGR) is associated with enhanced inflammatory activity, poor skeletal muscle glucose metabolism, and pancreatic β cell dysfunction that persist in offspring. We hypothesized that targeting heightened inflammation in IUGR-born neonatal lambs by supplementing anti-inflammatory ω-3 polyunsaturated fatty acids (ω-3 PUFAs) would improve metabolic outcomes. Methods: Maternal heat stress was used to produce IUGR lambs, which received daily oral boluses of ω-3 PUFA Ca²⁺ salts or placebo for 30 days. Results: Greater circulating TNFα and semitendinosus IL6R in IUGR lambs were fully resolved by ω-3 PUFA, and impaired glucose-stimulated insulin secretion, muscle glucose oxidation, and hypertension were partially rescued. Impaired glucose oxidation by IUGR muscle coincided with a greater glycogen content that was completely reversed by ω-3 PUFA and greater lactate production that was partially reversed. Ex vivo O₂ consumption was increased in IUGR muscle, indicating compensatory lipid oxidation. This too was alleviated by ω-3 PUFA. Conversely, ω-3 PUFA had little effect on IUGR-induced changes in lipid flux and hematology parameters, did not resolve greater muscle TNFR1, and further reduced muscle β2-adrenoceptor content. Conclusions: These findings show that targeting elevated inflammatory activity in IUGR-born lambs in the early neonatal period improved metabolic outcomes, particularly muscle glucose metabolism and β cell function. Full article

Intrauterine growth restriction (IUGR) commonly occurs in pigs and poses a significant challenge to the swine industry. This study investigated the effect of fermented milk on growth performance and intestinal health in IUGR-affected piglets. A total of 24 28-day-old weaned piglets with IUGR were randomly assigned to a corn-soybean basal diet (control) or a basal diet mixed with fermented milk (3:1 w/v, treatment). The results showed that fermented milk increased the average daily gain and decreased the feed-to-gain ratio (p < 0.05). Fermented milk increased the villus height in the duodenum and decreased the jejunal crypt depth (p < 0.05). Pigs in the treatment showed higher activities of lipase, α-amylase, and sucrase in the duodenum, along with an elevation in jejunal sucrase activity (p < 0.05). The ileal glutathione concentration was increased by the treatment (p < 0.05). Moreover, fermented milk upregulated the protein expression of occludin and claudin-3 while decreasing the gene expression of interleukin 1 beta, interleukin 6, and tumor necrosis factor αlpha in the jejunum (p < 0.05). Collectively, these results indicate that dietary supplementation with fermented milk significantly improved growth performance through the enhancement of intestinal functions in IUGR piglets, highlighting the potential of fermented milk as a nutritional strategy to improve postnatal growth in IUGR piglets. Full article

Background: Monochorionic diamniotic (MCDA) twin pregnancies are at risk of complications, particularly selective intrauterine growth restriction. The objective of this study was to evaluate the two-year neurologic outcomes of the eutrophic newborns from monochorionic diamniotic twin pregnancies who were complicated by selective intrauterine growth restriction, compared to newborns from uncomplicated MCDA pregnancies. Our hypothesis was to determine whether selective IUGR in these pregnancies was specifically associated with a risk of delayed psychomotor development at two years old. Methods: We conducted a retrospective–prospective observational cohort study of children from pregnancies and deliveries which were monitored at Hospital Nord of Marseille between 2012 and 2021. The primary outcome measure was the comparison of the Ages and Stages Questionnaire (ASQ) scores at the age of two years between the two groups. The secondary outcome measure was a composite score including the following: neonatal death, grade III or IV intraventricular hemorrhage (IVH) at cerebral MRI or cranial ultrasound, periventricular leucomalacia (PVL) at brain MRI, bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) of stages II or III. Results: A total of 57 eutrophic children were included in the group from monochorionic twin pregnancies complicated by selective IUGR and 270 children in the group from MCDA twin pregnancies with no complications. The composite morbidity and mortality criterion, including neonatal death, grade III or IV IVH, the presence of PVL, BPD, and/or stage II or III NEC, was 11% in eutrophic newborns from the MCDA group with IUGR and 5% in the uncomplicated MCDA group, with no statistically significant difference (p = 0.18). The 2-year follow-up allowed for the comparison of a total of 38 eutrophic children from complicated pregnancies and 134 children from uncomplicated pregnancies. The median ASQ score at 24 months was 255 in the complicated pregnancy group and 240 in the uncomplicated pregnancy group, with no statistically significant difference (p = 0.27) after adjustment. Conclusions: Our study did not show a statistically significant difference in the neurodevelopmental follow-up of eutrophic children from monochorionic diamniotic twin pregnancies with selective intrauterine growth restriction compared to newborns from the same pregnancies without complications. Full article