Search Results (243)

The insulin-like growth factor (IGF) system regulates implantation, placental development, and angiogenesis in eutherian mammals. However, little is known about the changes in this system in equine placenta (chorioallantois; CA) and the endometrium (EN) during pregnancy, or the relationship to vascular endothelial growth factor (VEGF) expression. The current study investigated the expression of the IGF system components, namely the ligands (IGF1 and IGF2), their receptors (IGF1R, IGF2R, and INSR), and their binding proteins (IGFBPs and IGF2BPs) in equine CA at 45 days, 4, 6, 10, and 11 months of gestational age (GA) and immediately postpartum (PP), and in equine EN at 4, 6, 10, and 11 months GA. IGF1 immunolocalization and serum concentrations were also evaluated across gestation. IGF1 mRNA expression in CA increased from day 45 to peak at 6 months and then gradually declined to reach a nadir in PP samples. This profile correlated positively with the VEGF expression profile (r = 0.62, p = 0.001). In contrast, IGF2 expression in CA was not correlated with VEGF (p = 0.14). Interestingly, IGF2 mRNA was more abundant in equine CA than IGF1 (p < 0.05) throughout gestation. Among the IGFBPs investigated in CA, the expression of IGFBP2 and IGF2BP2 was highly abundant (p < 0.05) at day 45 compared to other GAs. Conversely, mRNA expression for IGFBP3 and IGFBP5 was more abundant (p < 0.05) in PP than at all investigated GAs. Immunohistochemistry revealed that IGF1 is localized in the equine chorionic epithelium (cytoplasm and nucleus). IGF1 serum concentrations peaked at 9 months and declined to their lowest levels PP. In conclusion, this study demonstrates a positive correlation between IGF1 and VEGF expression in equine CA during gestation, suggesting that the IGF system plays a crucial role in placental angiogenesis by regulating VEGF. Full article

Purpose: Our understanding of the influence of preterm birth and related perinatal exposures on early brain development is limited, hampering personalized optimization of neuroprotective strategies. This study assesses the effect of gestational age (GA) at birth on brain volumes at term-equivalent age (TEA) in infants without overt brain injury born across the GA spectrum. Methods: A cohort of infants born across the GA spectrum (25–40 weeks’ gestation) underwent 3T brain MRI around TEA (40–46 weeks postmenstrual age). Eight brain regions, intracranial and total tissue volumes were segmented using MANTiS (morphologically adaptive neonatal tissue segmentation toolbox). Segmentations were visually quality-checked and excluded if segmentation failed. Absolute TEA volume in relation to GA was assessed using univariate and multivariate (correction for postmenstrual age) linear regression analysis. Statistical significance was set at p < 0.05. Post hoc scatter plots of brain volumes relative to intracranial volumes were created. Results: Fifty infants were included (mean GA = 35.0 [SD = 3.3, range = 25.7–40.1] weeks). A higher GA at birth was significantly related to lower cerebrospinal fluid (p = 0.004) and amygdala (p = 0.02) volumes; no significant relation was found between GA and other volumes. Post hoc analyses showed positive trends between GA and several brain structures, including total brain tissue, cortical gray matter, deep gray matter, hippocampus, cerebellum and brainstem volumes. Conclusions: Our results suggest that GA has an effect on TEA brain volumes that is independent of brain lesions, with lower GA being associated with smaller brain tissue volumes and significantly larger cerebrospinal fluid volume. Preterm birth and related exposures may thus affect early brain growth and contribute to neurodevelopmental challenges encountered by preterm-born children. Full article

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: Hypoxic–ischemic encephalopathy (HIE) is a leading cause of severe neurological impairments in childhood. Therapeutic hypothermia (TH) is both safe and effective in neonates born at ≥36 weeks gestation with moderate to severe HIE. We aimed to evaluate short-term outcomes—including brain injury detected on magnetic resonance imaging (MRI)—in infants born at 34–35 weeks of gestation drawing on our clinical experience with neonates under 36 weeks of gestational age (GA). Methods: In this retrospective cohort study, 20 preterm infants with a GA of 34 to 35 weeks and a matched cohort of 80 infants with a GA of ≥36 weeks who were diagnosed with moderate to severe HIE and underwent TH were included. Infants were matched in a 1:4 ratio based on the worst base deficit in blood gas and sex. Maternal and neonatal characteristics, brain MRI findings and short term outcomes were compared. Results: Infants with a GA of 34–35 weeks had a lower birth weight and a higher rate of caesarean delivery (both p < 0.001). Apgar scores, sex, intubation rate in delivery room, blood gas pH, base deficit and lactate were comparable between the groups. Compared to infants born at ≥36 weeks of GA, preterm neonates were more likely to receive inotropes, had a longer time to achieve full enteral feeding, and experienced a longer hospital stay. The mortality rate was 10% in the 34–35 weeks GA group. Neuroimaging revealed injury in 66.7% of infants born at 34–35 weeks of gestation and in 58.8% of those born at ≥36 weeks (p = 0.56). Injury was observed across multiple brain regions, with white matter being the most frequently affected in the 34–35 weeks GA group. Thalamic and cerebellar abnormal signal intensity or diffusion restriction, punctate white matter lesions, and diffusion restriction in the corpus callosum and optic radiations were more frequently detected in infants born at 34–35 weeks of gestation. Conclusions: Our study contributes to the growing body of literature suggesting that TH may be feasible and tolerated in late preterm infants. Larger randomized controlled trials focused on this vulnerable population are necessary to establish clear guidelines regarding the safety and efficacy of TH in late preterm infants. Full article

Background/Objectives. Previous research with extremely and very preterm children indicates that these children obtain significantly lower results in executive functions (EFs) and in reading skills than full-term (FT) children. The comparison results do not seem to be so clear when other PT children in lower-risk conditions are studied. Many studies with typically developing and preterm (PT) children indicate that reading ability is determined, in part, by EFs. Therefore, the study of EFs and reading and their relationships in low-risk PT children is pertinent. Methods. In the present study, 111 PT children, classified into three groups with different ranges of gestational age (GA), and one group of 34 FT children participated in a longitudinal study, carried out from 4 to 9 years of age. The results obtained from the four groups in different EFs measured at 4, 5, and 8 years of age, and in reading skills at 9 years of age were compared. The possible effects of EFs on reading skills were studied through multiple linear regression analyses. Results. The results obtained indicate that no significant difference was found between FT children and any of the GA groups of PT children, either in EFs or reading skills. The effect of EFs on reading skills was low to moderate. Verbal and non-verbal working memory had a positive significant effect on decoding skills (letter names, same–different, and word reading), but not on reading comprehension processes. Higher-order EFs (cognitive flexibility and planning), as well as inhibitory control, showed positive effects on reading comprehension skills. The effects of the different EFs varied depending on the reading process. Conclusions. In conclusion, low-risk PT children do not differ from FT children in their competence in EFs or reading skills. There are long-lasting effects of EFs, measured several years before, on reading skills measured at 9 years of age. Full article

Background/Objectives: The development of normal fetal cardiac function, a dynamic process that has not yet been precisely documented throughout the literature, is difficult to quantify by classic echocardiography. Our aim was to analyze the function of the fetal myocardium through speckle tracking and establish reference values for global and segmental longitudinal strain for both ventricles in fetuses with a gestational age (GA) between 22 and 39 weeks. Methods: We conducted a prospective study in which 170 fetuses underwent echocardiographic evaluation and those 150 that were eligible for the study underwent offline speckle tracking analysis. Results: A mixed-design ANOVA model with Greenhouse–Geisser correction showed no significant differences in regional strain measurements among GA groups (F [2, 147] = 1.25, p = 0.289) but showed significant differences in regional strain measurements among the right ventricle (RV), left ventricle (LV), and interventricular free wall (Greenhouse–Geisser F [1.3, 195.2] = 45.70, p < 0.001, GG ε = 0.66, original df = 2, 294). The wall-by-segment interaction term of the model was statistically significant for regional strain (Greenhouse–Geisser F [2.7, 394.2] = 27.00, p < 0.001, GG ε = 0.67, original df = 4, 588), while the segment-by-gestational age group term had a tendency toward statistical significance (Greenhouse–Geisser F [3.0, 221.4] = 2.21, p = 0.088, GG ε = 0.75, original df = 4, 294). The results of Welch’s ANOVA model showed no significant difference in right-ventricle peak global longitudinal strain (pGLS) between GA groups (F [2.0, 92.2] = 0.52, p = 0.5972) and global longitudinal strain measurements (F [2.0, 89.6] = 27.00, p = 0.3733). Conclusions: The reference values for longitudinal strain, represented by the pGLS for LV, ranged from −20.79 to −8.05 for fetuses with a GA between 22 and 27 weeks, from −20.14 to −8.99 for fetuses with a GA between 28 and 33 weeks, and from −20.19 to −8.88 for fetuses with a GA between 34 and 39 weeks. For RV pGLS, the reference values were between −18.99 and −6.35, also depending on GA. Reference ranges for the large gestational groups studied can help us to recognize subtle changes in fetal cardiac function. Full article

Background/Objectives: Optimal feeding position may contribute to improving the quality and safety of bottle-feeding in premature infants. The aim of this study was to compare the advantages of right side-lying (R-SLP) and left side-lying (L-SLP) positioning during the bottle-feeding of preterm infants. Methods: The randomized study included eight neonates (n = 8) born at ≤34 weeks of gestational age (GA). Four bottle-feeding sessions were conducted for each newborn: two in the R-SLP and two in the L-SLP position. Levels of oxygen saturation (SpO₂) and heart rate (HR) were measured as indicators of physiological stability. The qualitative aspects of feeding included total time of SpO₂ declines to ≤85%, the newborn’s alertness level based on the Neonatal Behavioral Assessment Scale (NBAS), and the number of possetings, regurgitations, and choking episodes. The volume of milk consumed and the duration of each feeding session were also recorded. Results: The L-SLP position was characterized with higher SpO₂ (p = 0.042) at the 10th minute after feeding and lower HR (p = 0.022) at the end of feeding. Greater milk intake (p = 0.042), shorter feeding duration (p = 0.021), and shorter duration of SpO₂ declines to ≤85% (p = 0.025) were also observed in L-SLP. No differences were found in alertness level, or in the number of choking episodes, possetings, or regurgitations compared to R-SLP. Conclusions: This pilot study suggests the potential efficacy of the L-SLP position during bottle-feeding of premature infants. The results require the need for larger studies to confirm the potential benefits of using L-SLP. Full article

Background/Objectives: To identify the risk factors and clinical outcomes of persistent pulmonary hypertension of the newborn (PPHN) in very low birth weight (VLBW) infants in a resource-limited setting. Methods: We conducted a 1:4 matched case–control study in a Thai neonatal unit between 2014 and 2023. Neonates born at a gestational age (GA) < 32 weeks and with a birth weight (BW) < 1500 g were included. Neonates who died in the delivery room or had major congenital anomalies were excluded. Matching was based on GA, BW, year of birth, and endotracheal intubation at birth. Conditional logistic regression analysis was performed. Results: Over the 10-year study period, the incidence of PPHN among VLBW neonates was 4.6% (31/667). After matching, there were 31 cases and 124 controls. In univariable analysis, PPHN was significantly associated with lower 1 min and 5 min Apgar scores; however, no significant association remained in multivariable analysis. PPHN was significantly associated with composite adverse outcomes—including mortality and major morbidities (adjusted odds ratio [aOR] = 7.51, 95% confidence interval [CI]: 2.41–23.40), mortality alone (aOR = 2.88, 95% CI: 1.06–7.63), major morbidities (aOR = 2.99; 95% CI: 1.29–6.95), and severe neurological injury (aOR = 4.44, 95% CI: 1.56–12.59). Daily hospital costs were also higher in PPHN cases, with an average increase of 97.1 USD. Conclusions: In VLBW infants, PPHN was associated with a lower Apgar score and surfactant administration. PPHN was significantly linked to adverse outcomes, particularly mortality, major morbidities, and severe neurological injury. Full article

Background/Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by increased pulmonary vascular resistance, resulting in severe hypoxemia. This study determined the factors associated with increased risk of mortality and survival rate in infants with PPHN. Methods: This retrospective study was conducted between 2010 and 2023. The risk factors for mortality were assessed by Cox’s proportional hazard models, and the Kaplan–Meier survival curve was used to analyze the survival rates. Results: This study included 233 neonates with PPHN. Gestational age (GA) less than 28 weeks (adjusted hazard ratio [AHR] = 5.46, 95% confidence interval [CI]: 2.25–13.24, p < 0.001), Small for gestational age (SGA) (AHR = 2.93, 95% confidence interval [CI]: 1.24–6.92, p = 0.026), acute kidney injury (AKI) (AHR = 2.48, 95% CI: 1.27–4.84, p = 0.01), pneumothorax (AHR = 3.03, 95% confidence interval [CI]: 1.48–6.21, p = 0.003), vasoactive-inotropic score (VIS) at 24 h of age (AHR = 1.0026, 95% confidence interval [CI]: 1.0004–1.005, p = 0.026), and score for neonatal acute physiology II (SNAP-II) ≥ 43 (AHR = 4.03, 95% CI: 1.66–9.77, p = 0.005) were associated with an increased risk of mortality. The overall survival rate was 82.4%; it rose from 63.8% to 87.1% after inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) were introduced (p < 0.001). The cumulative survival rates at the end of the 30 days were 62.1% (95% CI: 49.0–78.7) in the Pre-iNO era and 87.5% (95% CI: 82.7–92.6) in the Post-iNO/ECMO era, respectively (p < 0.001). Conclusions: GA less than 28 weeks, SGA, AKI, pneumothorax, high VIS and SNAP-II scores were associated with mortality in infants with PPHN. The improvement in the survival rate was related to the provision of advanced care, including iNO and ECMO therapy. 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

Aim: To assess the inter-rater agreement and accuracy of human experts’ estimate of EEG maturational age (EMA) and a computer algorithm’s estimate of EMA over the first days after birth in a cohort of normally developing preterm infants. In addition, we explore the influence of post-natal age (PNA) on EMA estimates. Methods: Analysis was performed on EEG records from newborns determined appropriate for gestational age (GA) with favorable neurodevelopment at 2 years of age and without significant neurological compromise at time of EEG monitoring. Three 1h epochs of EEG were selected from 29 newborns with GA ranging from 23 to <32 weeks, within 72 h of birth. EEG epochs were visually assessed by two pediatric neurologists and a computer algorithm. In addition, the full, long-duration EEG recording of each newborn was assessed by one pediatric neurologist. EMA estimates were compared to GA using Pearson’s correlation coefficient (r) and bias and standard deviation of error (SDE). Intra-newborn agreements for the EMA estimates were assessed using standard deviation. Linear mixed-effects models were used to quantify the effect of PNA on EMA estimates. Results: The algorithm provides a more accurate estimate of GA using 1 h EEG epochs for correlation and bias: algorithm r = 0.83 vs. experts r = 0.60 and 0.66, p < 0.05 for n = 29; algorithm bias = −0.8 days vs. experts’ bias = 3.6 and 7.0 days, p < 0.01 for n = 29. SDE of 8.7 days for the algorithm was not significantly lower compared to the experts’ SDE = 12.4 and 13.2 days, p > 0.05. The algorithm has higher intra-newborn agreement compared to the experts: algorithm SDE = 4.9 days vs. experts SDE = 7.4 and 7.4 days, p = 0.027. For the two experts, increasing PNA is associated with an increase in EMA estimates of 6.6 days/days and 3.7 days/days. The assessment of full, long-duration EEG recordings improved the experts’ estimate of EMA (r = 0.82; SDE = 9.2 days). Conclusions: Automated analysis outperforms visual interpretation of the EEG at estimating EMA for short-duration EEG recordings. PNA is an important factor in EMA estimates. Full article

Background: We recently reported that the transcutaneous bilirubinometer (TCB) tends to underestimate the severity of neonatal jaundice (NJ). We hypothesize that the cumulative ambient light exposure contributes to the discrepancy. Objectives: This study aimed to identify factors that affect the TCB underestimation. Methods: We analyzed prospectively collected data over a twenty-month period at a level III medical facility. Neonates at risk for NJ who couldn’t secure an appointment with the primary practitioner were followed by the nursery team. Neonates who had phototherapy or forehead bruises were excluded. Concurrently collected total serum bilirubin (TSB) was determined by the diazo method. The primary endpoint was the discrepancy between TCB and the corresponding TSB (TCB-TSB). A mixed-effects model was used to assess the correlation between (TCB-TSB) and potential contributors, including visit age (in hours), gestational age (GA), sex, TSB, season, birth weight, and race. Results: There were 795 visits for 559 neonates, including 341 males, 179 white, 235 black, 103 Hispanic, 41 Asian, and one unrecorded race. The TSB ranged between 1.8 and 33.9 mg/dL. The (TCB-TSB) ranged between −20.0 and 6.4 mg/dL. The median GA and birth weight were 38.7 weeks and 3214.5 g. The visits occurred between 48 and 381 h of age. 133, 148, 132, and 146 visits were in Spring, Summer, Autumn, and Winter, respectively. Fifty-four neonates (9.7%) were admitted for management. 500 sternum TCB readings were also collected from 350 neonates together with the corresponding forehead TCBs. We found that the forehead (TCB-TSB) was significantly less in winter than in spring and summer (p = 0.0014 and 0.0003, respectively). There was a negative correlation between forehead (TCB-TSB) and visit age in hours (p = 0.0006). After adjusting for visit age and season, the (TCB-TSB) is significantly correlated with TSB (p < 0.0001). Similar findings were also seen in the sternum (TCB-TSB) except for the season (p = 0.0808). Conclusions: Cumulative ambient light exposure and the severity of NJ may contribute to (TCB-TSB). Full article

Background/Objectives: It is challenging to obtain all the required views for a fetal anatomy ultrasound examination, so exams are often incomplete. Our objective was to develop and demonstrate quantitative methods to assess the overall rate of incomplete exams for an ultrasound practice and for individual examiners. Methods: We performed a retrospective quality review of all detailed fetal anatomy exams at seven maternal–fetal medicine practices in 2024 with singleton pregnancies and cardiac activity present. The exams were considered incomplete if any of the 36 required anatomy views were reported as inadequate. The analysis focused on exams at a gestational age (GA) of 18.0 to 23.9 weeks. The rates of incomplete exams were tabulated across practices and for individual sonographers and physicians. Multivariable logistic regression was used to adjust for known covariates. Results: In total, 15,723 detailed fetal anatomy exams were performed at 18.0–23.9 weeks of gestation. Incomplete exams were significantly more common with maternal obesity, prior cesarean, maternal age < 35 years and GA < 19 weeks. There were significant between-practice differences in the rate of incomplete exams, varying from 1% to 53%. Incomplete exams had a median of four inadequate views (interquartile range 2–7). Practices also varied significantly in the rate of missing measurements for nuchal fold (0 to 9%) and nose bone length (11–100%). There were significant between-individual differences in the rate of incomplete exams. The tabulation of specific views showed some individuals with very high rates of inadequate views of certain elements. Conclusions: For some practices, there is a need for practice-wide quality improvement to increase the rate of measurement of the nuchal fold and nose bone. For selected individuals, the tabulation of which anatomy elements were inadequate can identify areas for targeted education or mentorship. We suggest strategies and software enhancements that may reduce the rate of incomplete exams. Sample data and statistical analysis scripts are provided for those who wish to adopt these methods to review their own data. Full article

Objective: To evaluate and compare whether the presence of a nuchal cord (NC) and its characteristics had a negative impact on perinatal outcomes during delivery. Methods: This was a retrospective cohort study that analyzed the medical records of pregnant women from March 2020 to June 2023. Pregnant women were divided into groups with and without an NC. Singleton pregnancies ≥ 37 weeks were included, excluding fetal malformations, chromosomal anomalies, and cases with missing data and cord blood gas. Results: Of the 3364 medical records analyzed, 466 were included—366 without and 100 with an NC. Among the cases with an NC, 91% had one loop and 9% had ≥ two loops; 82% were loose and 18% were tight. Pregnant women with an NC had a higher gestational age (39.7 vs. 39.1 weeks, p = 0.006), fewer deliveries (1.0 vs. 2.0, p = 0.035), and a higher prevalence of cesarean sections (99% vs. 60.4%, p < 0.001). An NC was associated with a lower Apgar score at the 1st minute (8 vs. 9, p = 0.014) and higher arterial cord blood pH (7.27 vs. 7.24, p = 0.020). The presence of a tight cord was significantly associated with a 7.52-fold increased risk of an Apgar score < 7 at the 1st minute [x²(1) = 5.92, OR: 7.52, 95% CI: 1.51–37.31, R² Nagelkerke: 0.14, p = 0.014]. Conclusions: There was no effect of the presence of an NC on adverse perinatal outcomes. However, the presence of a tight NC was associated with an increased risk of an Apgar score < 7 at the 1st minute, but no other effect on neonatal outcomes. Full article