Search Results (215)

Background: Nutrition is of paramount importance during early development, since suboptimal growth in this period of life is linked to adverse long- and mid-term outcomes. This is particularly relevant for preterm infants, who fail to thrive during the first weeks of life and develop extrauterine growth restriction (EUGR). This group of premature babies represents an interesting population to investigate using a metabolomic approach to optimize nutritional intake. Aims: To analyse and compare the urinary metabolomic pattern at birth of preterm infants with and without growth restriction at 36 weeks of postmenstrual age or at discharge, searching for putative markers of growth failure. Methods: We enrolled preterm infants between 23 and 32 weeks of gestational age (GA) and/or with a birth weight <1500 g, admitted to the Neonatal Intensive Care Unit (NICU) at the Department of Women’s and Children’s Health of Padova University Hospital. We collected urinary samples within 48 h of life and performed untargeted metabolomic analysis using mass spectrometry. Results: Sixteen EUGR infants were matched with sixteen non-EUGR controls. The EUGR group showed lower levels of L-cystathionine, kynurenic acid, L-carnosine, N-acetylglutamine, xanthurenic acid, aspartylglucosamine, DL5-hydroxylysine-hydrocloride, homocitrulline, and L-aminoadipic acid, suggesting a lower anti-inflammatory and antioxidant status with respect to the non-EUGR group. Conclusions: Metabolomic analysis suggests a basal predisposition to growth restriction, the identification of which could be useful for tailoring nutritional approaches. Full article

Background/Objectives: Infants with high-output enterostomies often require prolonged parenteral nutrition (PN), increasing risks of infections, liver dysfunction, and impaired growth. Mucous fistula refeeding (MFR) is proposed to enhance intestinal adaptation, weight gain, and distal bowel maturation. This systematic review and meta-analysis assessed its effectiveness, safety, and technical aspects. Methods: Following PRISMA guidelines, studies reporting MFR-related outcomes were included without data or language restrictions. Data sources included PubMed, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Library, and UpToDate. Bias risk was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Meta-analysis employed random- and fixed-effects models, with outcomes reported as odds ratios (ORs) and 95% confidence interval (CI). Primary outcomes assessed were weight gain, PN duration, and complications and statistical comparisons were made between MFR and non-MFR groups. Results: Seventeen studies involving 631 infants were included; 482 received MFR and 149 did not. MFR started at 31 postoperative days and lasted for 50 days on average, using varied reinfusion methods, catheter types, and fixation strategies. MFR significantly improved weight gain (4.7 vs. 24.2 g/day, p < 0.05) and reduced PN duration (60.3 vs. 95 days, p < 0.05). Hospital and NICU stays were also shorter (160 vs. 263 days, p < 0.05; 122 vs. 200 days, p < 0.05). Cholestasis risk was lower (OR 0.151, 95% CI 0.071–0.319, p < 0.0001), while effects on bilirubin levels were inconsistent. Complications included sepsis (3.5%), intestinal perforation (0.83%), hemorrhage (0.62%), with one MFR-related death (0.22%). Conclusions: Despite MFR benefits neonatal care, its practices remain heterogeneous. Standardized protocols are required to ensure MFR safety and efficacy. Full article

Background: The worldwide prevalence of FGR is about 13% and can lead to various adverse perinatal outcomes, including preterm birth, stillbirth, and neonatal mortality. Hypoxia-Inducible Factor-1 (HIF-1) is an important regulator of oxygen homeostasis in humans and is crucial for placental development. The aim of this study is to determine the pattern of HIF-1A expression in placenta, and to correlate its association with preeclampsia, fetal growth restriction and adverse perinatal outcomes. Methods: This study comprised a total of 158 cases with 42 cases of mother having babies with fetal growth restriction (FGR), 39 cases of mother with preeclampsia (PE), 35 cases of mother with preeclampsia and fetal growth restriction and 42 controls. The expression of HIF-1A was evaluated in various placental cell types, including cytotrophoblasts, syncytiotrophoblasts, fetal endothelial cells, maternal endothelial cells, and decidual cells. Results: The expression of HIF-1A in placental decidual cells of mother with FGR (21/42, 50%, p < 0.0001), PE (25/39, 64.1%, p < 0.0001) and PE with FGR (12/35, 34.3%, p < 0.0001) were significantly increased compared to controls (1/42). Intriguingly, HIF-1A expression was significantly reduced in the placental cytotrophoblasts and syncytiotrophoblasts of mother with PE and FGR (2/35, 5.7%) compared to PE alone (11/39, 28.2%) (p = 0.0142). Conclusions: We found that increased HIF-1A expression in the nuclei of decidual cells was observed in the mothers of babies with FGR, both with and without PE. While HIF-1A expression in the cytotrophoblasts and syncytiotrophoblasts was significantly reduced between mothers with PE and mothers with PE and FGR. This suggests HIF-1A expression might play a role in the pathogenesis of FGR. Full article

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 h of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population. Full article

Background and Objectives: Electronic fetal heart rate monitoring is mandatory for preterm labor. Moderate to late preterm neonates have an increased risk of overall morbidity, neonatal intensive care (NICU) admission, and consequently, medication use. The outcome of preterm neonates > 32 weeks of gestation in relation to three-tiered fetal heart rate (FHR) categorization was analyzed. Materials and Methods: This was a single-center, retrospective case-control study conducted from January 2021 to December 2023. The study included 25 FGR and 131 control cases born from 33 to 36 6/7 gestational weeks. Outcome was defined as the need for assistance after birth in first 15 min of life, respiratory outcome, and first day dopamine use and fresh frozen plasma transfusion. Maternal characteristics as risk factors for non-normal categories within three-tiered FHR categorization were also analyzed. Results: There was no significant difference in neonatal outcome among groups, except significantly lower 1 min APGAR and longer LOS in the FGR group. An increasing category within the three-tiered FHR categorization positively correlated with the need for assistance after birth, respiratory outcome, dopamine use, fresh frozen plasma transfusion, and length of hospital stay. Negative correlations were revealed between the increasing category within the three-tiered FHR categorization and first and fifth minute APGAR scores. Oligohydramnios and male sex were risk factors for non-normal categories within three-tiered FHR categorization. The correlation was tested using the Spearman correlation coefficient. A logistic regression model was employed to identify maternal risk factors for the non-normal category within three-tiered FHR categorization. All differences were statistically significant (p < 0.05). Conclusions: The increasing category within three-tiered FHR categorization may alert neonatologists to be highly suspicious of RDS, respiratory support, dopamine use, and fresh frozen plasma transfusion in neonates born from 33 to 36 6/7 gestational weeks. Oligohydramnios and male sex increase the probability for non-normal categories in the three-tiered FHR categorization. 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

Maturity-onset diabetes of the young (MODY)—a monogenic form of diabetes—accounts for approximately 1–2% of all diabetes cases, with GCK-MODY being the second most commonly diagnosed type. Although the inherited nature of the disease implies that the interplay between maternal glycemia and fetal genotype directly influences neonatal outcomes, clinical guidelines for MODY-complicated pregnancies remain underdeveloped. A systematic literature search in the PubMed, Scopus, Web of Science, and Cochrane databases was conducted following the PRISMA guidelines. The study protocol has been logged in the PROSPERO registry with the identification number CRD42024609390. Data, such as MODY type, the gestational age at delivery, mode of delivery, insulin administration, mutational status of the fetus, fetal birthweight (FBW), occurrence of small-/large-for-gestational age fetus, shoulder dystocia, and neonatal hypoglycemia, were extracted and evaluated. Among 19 studies selected for the final analysis, 15 investigated perinatal outcomes in the GCK-MODY variant. Women diagnosed with GCK-MODY treated with insulin delivered approximately 1–2 weeks earlier than those managed with diet alone. FBW was significantly higher in GCK-negative as compared to GCK-positive offspring. Accordingly, fetal macrosomia was notably more common among unaffected neonates. In GCK-affected fetuses, insulin therapy was associated with a significantly lower FBW. Fetal genotype critically modifies perinatal outcomes in GCK-MODY pregnancies. In the absence of fetal genotyping, conservative management should be prioritized to mitigate the risks of fetal growth restriction and iatrogenic prematurity. As data regarding other types of MODY in pregnancy remain sparse, there is an urgent need for more research in this area. Full article

Background and Objectives: Inherited thrombophilia (IT) increases the risk of adverse pregnancy outcomes, but the benefit of low-molecular-weight heparin (LMWH) prophylaxis remains debated. This study aimed evaluate the effect of LMWH by analyzing outcomes in women with IT who received LMWH versus those who did not and also compare pregnancy complication rates before and after inherited thrombophilia diagnosis. Materials and Methods: We conducted a retrospective case–control study including 276 pregnant women with inherited thrombophilia and prior pregnancy complications and 276 healthy pregnant controls on delivery. The main outcome was the incidence of complications: preterm rupture of membranes, oligohydramnios, fetal growth restriction, preterm delivery, stillbirth, HELLP syndrome, gestational hypertension, deep vein thrombosis, and recurrent pregnancy loss. The effect of LMWH was assessed by comparing complication rates among inherited thrombophilia patients who received therapy versus those who did not. Results: Women with IT were older, had higher BMI, delivered earlier, and had neonates with lower birth weight compared to controls. In current pregnancies, LMWH was associated with reduced rates of preterm delivery, fetal growth restriction, gestational hypertension, and recurrent pregnancy loss, especially in factor V Leiden carriers. LMWH had little effect on low-risk genotypes and was not independently associated with outcome reduction. Conclusions: LMWH prophylaxis should be reserved for high-risk women with IT. Routine use in all IT pregnancies is not justified and may cause unnecessary risks and costs. Early screening, risk stratification, and individualized care are essential to optimize outcomes. 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

Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus’s failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these data cannot necessarily be extrapolated to prenatal hypoxia. In this regard, this study aims to describe the effect of gestational hypoxia on redox balance and apoptosis cell death mechanisms in the prefrontal cortex of guinea pigs. Ten Guinea pig (Cavia porcellus) pregnant dams were utilized in this study; five gestated in normoxia (Nx; three newborn males, and two females) and five gestated under chronic hypobaric hypoxia (Hx; two newborn males, and three females). We monitored the pregnancies by ultrasound examinations from gestational days 20 to 65 (term ~ 70). At birth, pups were euthanized, and the fetal brain was collected for cellular redox measurement, mitochondrial enzyme expression, and apoptosis assay. Gestation under hypoxia induced an imbalance in the expression of anti- and pro-oxidant enzymes, resulting in increased oxidative stress. Additionally, a decrease in cytochrome I and III expression and neuronal density in the neonatal prefrontal cortex was observed. Finally, DNA fragmentation was increased by the TUNEL assay in the brain tissue of newborns gestated under chronic hypoxia. Our findings demonstrate the association of gestational hypoxia with oxidative stress and neuronal death in newborns, which may predispose to neuronal dysfunction in adulthood. Full article

High-risk pregnancies (HRPs) constitute a significant global health issue due to their strong association with increased maternal and neonatal morbidity and mortality. Although pregnancy is generally characterized by positive expectations, the presence of maternal comorbidities, gestational complications, or adverse socioeconomic and environmental conditions can markedly elevate the probability of unfavorable outcomes. HRPs contribute disproportionately to complications such as preterm birth, fetal growth restriction, low birth weight, and congenital anomalies, which are key determinants of neonatal mortality and long-term developmental and health challenges. A broad spectrum of risk factors as well as insufficient prenatal care, underscores the complex nature of HRPs. These conditions necessitate a multidisciplinary management approach encompassing early risk identification, continuous monitoring, and individualized interventions. The neonatal prognosis in such contexts is strongly influenced by gestational age at delivery, birth weight, the standard of neonatal care, and the underlying etiological factors driving preterm or complicated deliveries. Preventive strategies including comprehensive prenatal screening, systematic antenatal follow-up, and timely referral to specialized perinatal care centers are essential for reducing the burden of HRPs. Furthermore, addressing social determinants of health—such as low socioeconomic status and limited access to healthcare—is critical for optimizing maternal and neonatal outcomes. This review consolidates current evidence on the epidemiology, etiological factors, and clinical implications of high-risk pregnancies, emphasizing the necessity of an integrative, preventive, and multidisciplinary framework to mitigate adverse neonatal outcomes and improve long-term health trajectories. Full article

The complications observed in preterm infants are largely attributable to underdeveloped organ systems and inadequate nutritional stores at birth. Insufficient nutritional support can further exacerbate persistent sequelae, such as bronchopulmonary dysplasia (BPD), metabolic bone disease of prematurity (MBDP), and retinopathy of prematurity (ROP). As a result, clinicians have collaborated to develop optimal nutrition strategies for preterm neonates. However, these clinical nutrition plans may be hindered by several factors, including fluid restrictions due to patent ductus arteriosus (PDA) and delayed enteral nutrition following necrotizing enterocolitis (NEC). Modified strategies for specific conditions can help prevent further deterioration, but inadequate nutritional support may limit organ growth and contribute to additional complications. Achieving an optimal balance between nutritional support and managing specific medical conditions varies across institutions. In addition to fluid balance and energy intake, supplementary nutrition—such as vitamins and probiotics—plays a crucial role in disease prevention. Drawing on recent evidence and our clinical experiences with neonatal nutritional strategies, this review article summarizes the specialized nutritional management required for preterm neonates with conditions such as BPD, NEC, MBDP, PDA, and ROP. Full article

Background/Objective: Preeclampsia is a hypertensive disorder associated with pregnancy that has a significant impact on maternal and neonatal health and has the potential to result in significant perinatal adverse outcomes. Maternal education has been proposed as a protective factor during pregnancy; however, its role in preeclamptic pregnancies remains unclear. This study aimed to explore the relationship between maternal education level, as defined by ISCED classification, and neonatal outcomes (birth weight, gestational age, and APGAR score) in pregnancies complicated by preeclampsia. Methods: A retrospective case-control analysis was conducted on 674 deliveries at a single tertiary center in Western Romania between January 2022 and August 2024. Neonatal outcomes, specifically birth weight, gestational age, and APGAR scores were studied and stratified into three ISCED-based maternal education subgroups. Statistical analyses, including ANOVA, chi-square tests, and logistic regression, were used to analyze the effect of maternal education, with confounders such as maternal age and chronic hypertension being controlled for. Results: Preeclampsia was associated with lower birth weight (p < 0.001), gestational age at birth (p < 0.001), and APGAR scores (p < 0.001) than the control group. Maternal level of education was associated with better neonatal outcomes in the preeclamptic group, with lower odds of fetal growth restriction (OR = 0.68, p = 0.03) and preterm birth; however, the effect was less pronounced in the control group. Conclusions: Maternal education partially mitigates the adverse effects of preeclampsia on neonatal well-being, birth weight, and gestational age at birth. These findings underscore the importance of incorporating maternal education into prenatal care programs to improve perinatal outcomes, with a special focus on high-risk pregnancies. Full article

Background: Thrombophilia is a prothrombotic disorder that can affect pregnancy outcomes, potentially leading to maternal complications, fetal growth restriction, and adverse perinatal events. However, the precise relationship between thrombophilia and these outcomes remains under investigation, and the impact of hematological, renal, hepatic, and coagulation alterations in thrombophilic pregnancies is not yet fully understood. This study aims to examine the maternal and neonatal consequences of thrombophilia by analyzing key laboratory parameters and perinatal outcomes in affected pregnancies. Methods: A retrospective observational study was conducted on 251 pregnant women, divided into thrombophilic (n = 226) and non-thrombophilic (n = 25) groups. Data on maternal demographics, laboratory parameters (hematological, metabolic, renal, hepatic, and coagulation markers), obstetric outcomes, and neonatal characteristics were extracted from medical records. Statistical analysis included t-tests, chi-square tests, and Pearson correlation analysis to assess the association between thrombophilia and clinical outcomes. Results: Thrombophilic pregnancies were associated with significantly lower fibrinogen levels (p = 0.036) and decreased INR (p = 0.006), suggesting a hypercoagulable state. Renal function was affected, as evidenced by elevated urea (p = 0.012) and creatinine (p = 0.009), indicating a predisposition to kidney dysfunction. Neonates from thrombophilic pregnancies exhibited slightly lower Apgar scores at 1 and 5 min, though the differences were not statistically significant (p = 0.101, p = 0.131). NICU admission rates were comparable between groups (p = 0.317), suggesting that thrombophilia may not be a major determinant of neonatal intensive care needs. However, gestational age and birth weight remained the strongest predictors of neonatal vitality (p < 0.001), while coagulation abnormalities and renal dysfunction correlated with poorer perinatal outcomes. Conclusions: Thrombophilia is associated with altered coagulation profiles, renal dysfunction, and potential risks for maternal complications. While neonatal outcomes were not significantly different, the observed trends suggest the need for enhanced monitoring in thrombophilic pregnancies. Early intervention, thromboprophylaxis, and individualized management strategies may improve maternal and neonatal prognosis. Further research is needed to refine preventive strategies and optimize therapeutic approaches in high-risk pregnancies. 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