Search Results (172)

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: Anemia and preeclampsia are common and independently associated with adverse neonatal outcomes. Their combined effect, however, remains insufficiently explored. This study aims to evaluate the impact of second-trimester maternal anemia on neonatal outcomes in pregnancies complicated by preeclampsia, and to assess its predictive value for preterm birth and NICU admission. Methods: We conducted a retrospective cohort study including 3517 singleton births from a Romanian tertiary maternity hospital between October 2023 and December 2024. A total of 295 preeclamptic pregnancies were stratified by anemia severity (none, mild, moderate-to-severe) and compared with 428 matched non-preeclamptic anemic pregnancies matched by closest-neighbor selection. Neonatal outcomes included birthweight, gestational age, anthropometric parameters, Apgar score, preterm birth, and NICU admission. Logistic regression and ROC curve analysis were performed using anemia severity as a predictor. Results: Moderate-to-severe anemia in preeclamptic pregnancies was associated with significantly lower birthweight (2618 ± 461 g), shorter gestational age (36.6 ± 2.0 weeks), and higher preterm birth (41.1%) and NICU admission rates (40.0%) were compared to non-anemic counterparts. Each increase in anemia severity conferred 84% higher odds of preterm delivery (OR = 1.84; AUC = 0.63) and a 49% increase in NICU admission (OR = 1.49; AUC = 0.58). Youden’s indices were 0.25 and 0.14, respectively. Conclusions: Maternal anemia is associated with increased neonatal morbidity in preeclamptic pregnancies, with moderate predictive value for preterm birth. These findings support the integration of early anemia screening and risk stratification into hypertensive pregnancy protocols to improve perinatal outcomes. Full article

Background/Objectives: Recent data on long-term consequences of prematurity on bone health are conflicting. The aim of this study was to assess the metabolic bone profile and bone mineral density (BMD) in prepubertal children born prematurely and to examine possible associations between bone health parameters and perinatal morbidity factors. Methods: This cross-sectional observational study included 144 children of mean (SD) age 10.9 (1.6) years: 49 children born very preterm (≤32 gestational weeks), 37 moderate-to-late preterm (32⁺¹ to 36⁺⁶ gestational weeks), and 58 born at term (controls). Serum levels of calcium/Ca, phosphorus/P, alkaline phosphatase/ALP, 25-hydroxyvitamin D/25(OH)D, bone formation markers (osteocalcin/OC, procollagen type I C-terminal propeptide/PICP, and insulin growth factor-1/IGF-1), and bone resorption markers (serum tartrate-resistant acid phosphatase 5b/bone TRAP5band urinary calcium-to-creatinine ratio) were measured. Total-body and lumbar-spine BMD and BMD Z-scores were calculated using dual-energy X-ray absorptiometry/DXA. Results: Children born very preterm showed significantly higher ALP, OC, PICP, and bone TRAP5b levels compared to controls, as well as compared to children born moderate-to-late preterm. Total-body and lumbar-spine BMD Z-scores were significantly lower in the very preterm-born group compared to controls. Gestational diabetes, preeclampsia, and bronchopulmonary dysplasia were associated with lower total-body BMD in the very preterm-born population. Conclusions: Preterm birth is associated with impaired metabolic bone profile and lower total-body and lumbar-spine BMD in childhood. Moderate-to-late preterm-born children exhibit altered metabolic bone parameters compared to very preterm-born children. Further research in children might allow better insight into the long-term impact of preterm birth on bone health. Full article

Background/Objective: We sought to address ongoing gaps in understanding the relationship between first-week percent maximal weight loss (MWL) and average first-week total fluid intake (TFI), enteral intake, and parenteral intake among premature newborns with adverse in-hospital outcomes born in low- and middle-income countries (LMICs). Methods: We evaluated newborns born <34 weeks gestation or <1500 g who survived at least 7 days at the St. Paul’s Hospital Millennium Medical College (SPHMMC) neonatal intensive care unit in Ethiopia. We performed univariate and multivariate regression models analyzing the first-week MWL, average TFI, parenteral, and enteral intake and their relationships with adverse in-hospital outcomes. Results: Among N = 490 moderately and very preterm newborns, multivariate regression models demonstrated that >13% MWL was associated with significantly increased odds of suspected necrotizing enterocolitis (NEC), culture-positive sepsis, retinopathy of prematurity (ROP), and a longer length of stay (LOS). An average enteral intake of >60 mL/kg/day was significantly associated with reduced odds of all-cause mortality, suspected NEC, culture-positive sepsis, ROP, and a shorter LOS, whereas an average parenteral intake of >60 mL/kg/day was associated with increased odds of in-hospital mortality, culture-positive sepsis, ROP, and a longer LOS. Conclusions: In moderately and very preterm neonates in an LMIC setting, >13% MWL is associated with adverse health outcomes. Increasing the average parenteral intake over the first week after birth among moderately and very preterm neonates is significantly associated with adverse in-hospital outcomes whereas increasing the average enteral intake is associated with improved outcomes. 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/Objectives: Prenatal adverse events may influence the development of complications of prematurity, including patent ductus arteriosus (PDA). We conducted a systematic review and Bayesian model-averaged (BMA) meta-analysis of observational studies exploring the association between hypertensive disorders of pregnancy (HDP) and the risk of PDA in preterm infants. Methods: PubMed/Medline and Embase databases were searched. We used BMA analysis to calculate Bayes factors (BFs). The BF₁₀ is the ratio of the probability of the data under the alternative hypothesis (H₁, presence of association) over the probability of the data under the null hypothesis (H₀, absence of association). Results: We included 41 studies (58,004 infants). BMA analysis showed moderate evidence in favour of H₀ for the association between HDP and any PDA (BF₁₀ = 0.20) as well as for the association between HDP and hemodynamically significant PDA (BF₁₀ = 0.27). Subgroup analyses based on the subtype of HDP showed that the moderate evidence in favour of H₀ was only conclusive (i.e., BF₁₀ < 0.33) for the associations of any PDA with preeclampsia (BF₁₀ = 0.30) and hemodynamically significant PDA with preeclampsia (BF₁₀ = 0.17). Conclusions: The currently available evidence suggests a lack of association between HDP and the risk of developing PDA. Full article

Objectives: Ritodrine, a tocolytic agent used to delay preterm labor, can cause several cardiovascular-associated adverse events (AEs). This study aimed to examine the relationship between gene polymorphisms in peroxisome proliferator-activated receptor gamma (PPARG) and PPARG coactivator-1α (PPARGC1A) and the occurrence of ritodrine-induced AEs. Additionally, a risk-scoring system was developed to identify patients at high risk of AEs. Methods: Patients aged 18 years or older who were administered ritodrine to manage preterm labor with intact membranes and uterine contractions occurring at 20–36 weeks of gestation were enrolled in this study. A total of 70 common PPARG and PPARGC1A variants (minor allele frequency ≥ 0.2) with low linkage disequilibrium (r² < 0.8) were selected from an Axiom™ Precision Medicine Research Array (AMPRA). Results: A total of 149 patients were included in the analysis. After adjusting for confounders (age, gestational age, and the maximum infusion rate), weight and rs2946385, rs35523565, and rs2240748 of PPARGC1A were identified as significant predictors associated with ritodrine-induced AEs. Based on the risk-scoring system, the predicted probabilities of AEs for patients with scores of 0, 1, 2, 3, 4, and 5 points were 4%, 9%, 18%, 35%, 55%, and 74%, respectively. The AUROC for the risk score predicting ritodrine-induced AEs was 0.729 (95% CI: 0.672–0.831, p < 0.001). Conclusions: This study indicates that ritodrine-induced AEs are related to PPARGC1A polymorphisms. A risk-scoring system based on genetic variants showed moderate predictive ability for ritodrine-induced AEs, suggesting potential utility in females with preterm labor. Full article

Background/Objectives: Iron deficiency anemia in pregnancy poses risks to mothers and infants. This study aimed to correlate maternal iron indices in the second trimester with cord blood indices and pregnancy outcomes. Methods: This prospective cohort study was nested within the RAPIDIRON Trial (Reducing Anaemia in Pregnancy in India) at Jawaharlal Nehru Medical College, Karnataka, India. A total of 292 pregnant women with moderate anemia who received oral iron supplementation were enrolled from April 2021 to May 2023. Maternal iron indices were measured at multiple time points and correlated with cord blood indices and pregnancy outcomes. Results: Increased hemoglobin levels were observed in mothers of preterm and term neonates from 8.92 ± 0.81 vs. 9.02 ± 0.77 g/dL at 12–16 weeks to 11.14 ± 1.31 vs. 10.73 ± 1.24 g/dL at 26–30 weeks. A similar trend was observed in mothers across birth weight groups. Ferritin and TSAT levels significantly increased in all outcome groups (p < 0.001), peaking at 20–24 weeks and then slightly declining at 26–30 weeks. Additionally, maternal sTfR levels significantly improved from the early (7.72 ± 1.33 vs. 7.51 ± 1.61) to late second trimester (5.87 ± 0.81 vs. 5.76 ± 1.11) in mothers of both anemic and non-anemic neonates (p < 0.001). Maternal sTfR in other outcome groups also showed a similar pattern. A negligible correlation was found between maternal and cord blood iron indices. Conclusions: Maternal iron indices increased from the early to mid-second trimester, followed by a slight fall in the late second trimester. Notably, higher iron indices were observed in mothers of preterm and low-birth-weight neonates. Full article

Bronchopulmonary dysplasia (BPD) is a severe chronic respiratory disease linked to preterm births. A scoping review was performed to identify risk factors for moderate and severe BPD to develop an evidence-based, early prognostic, globally recognized, and etiology/pathophysiology-based classification. The findings were then validated against a Japanese national database, the Neonatal Research Network Japan. After identifying histological chorioamnionitis, bubbly/cystic appearance on chest X-ray, and small-for-gestational-age infants as risk factors for severe BPD, BPD was divided into nine categories based on the presence or absence of these three risk factors. After consensus was reached using the Delphi method, public comments were requested, and the classification of BPD was finalized. This perspective introduces the new etiology/pathophysiology-based BPD classification, which should be used in research to better understand the respiratory prognosis and pathophysiology of BPD. Full article

Background: Moderate and late preterm infants (32–36 weeks of gestation) are at significant risk of developmental impairments. Incidence of white matter lesions, which are associated with developmental impairments in very preterm infants, remains underreported in this population. This study aimed to assess the incidence and clinical risk factors associated with brain lesions, particularly white matter lesions, in moderate and late preterm infants using term-equivalent MRI. Methods: This prospective observational study included 195 preterm infants born at 32+0–36+6 weeks of gestation and admitted to a tertiary NICU between 2019 and 2020. MRI findings at term-equivalent age were evaluated. Clinical risk factors were analysed using logistic regression. Results: Among the 195 infants, 23.6% had brain lesions on MRI, with white matter lesions (73.9%), specifically punctate white matter lesions, being the most common form of lesions. Vaginal delivery (odds ratio (OR) = 3.102, 95% confidence interval (CI) = 1.250–7.696, p = 0.015), larger birth weight z-scores (OR = 1.702, 95% CI = 1.118–2.591, p = 0.013), and intubation (OR = 2.948, 95% CI = 1.269–6.850, p = 0.012) were significant risk factors for white matter lesions. Conclusions: White matter lesions, particularly punctate white matter lesions, are common in moderate and late preterm infants. These lesions are associated with perinatal factors suggestive of delayed transition and inflammation. Future research should focus on detailed clinical care measures and neurodevelopmental assessments to identify modifiable risk factors for brain injury. Full article

Background/Objectives: Maternal milk feeding in the NICU (neonatal intensive care unit) for very low birth weight (VLBW) infants mitigates the effects of preterm birth. This single-center retrospective study analyzed data from VLBW infants born between 2005 and 2019 and investigated the impact on morbidity of exposure to Mother’s Own Milk (MOM), donor human milk (DHM), preterm formula (PF), during NICU hospitalization. The assessed outcomes included necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and late-onset sepsis (LOS). The study also examined the impact of a human milk-based feeding protocol on these outcomes, adjusting for confounding factors. Methods: Statistical analysis involved correlation tests and odds ratios to assess associations between feeding types and outcomes. Results: Surgical NEC occurred in 10% of infants fed exclusively with PF, 1.3% of those fed with DHM, and was completely absent in infants fed exclusively or partially with MOM. ROP across all stages was observed in 24.3% of cases, with severe ROP at 4.7%, and PF feeding was associated with a higher risk of severe ROP; the incidence of LOS was lower in infants fed human milk (−22%/−66%) compared to 10% in formula-fed infants. BPD affected 25.5% of infants, with moderate-to-severe BPD in 22.2%. The association between NEC, LOS, and feeding was statistically significant, even after adjusting for covariates. The type of milk had a significant impact on the incidence of severe forms of all outcomes (p < 0.001). The rate of exclusive MOM feeding increased over time, reaching 45% in 2018–2019. Conclusions: These findings highlight the role of human milk in preventing NEC and LOS, in reducing the risk of severe ROP and BPD, and in promoting MOM feeding, with rates increasing significantly when DHM is available. Full article

This study evaluated the differential expression of four placental markers—vitamin D receptor (VDR), Cluster of Differentiation 44 (CD44), osteopontin (OPN), and cyclooxygenase-2 (COX-2)—in response to pathogens, which may contribute to our understanding of pathogen-specific impacts on pregnancy outcomes. We immunohistochemically (IHC) analyzed placental tissues obtained from 70 healthy-term pregnant women in the control group and compared them to tissues obtained from 78 women with pregnancy above 24 weeks of gestation, single-pathogen vaginal infection, and premature rupture of membranes/preterm premature rupture of membranes (PROM/PPROM). We detected high expression of these four molecules in cases of Group B Streptococcus (GBS) and Ureaplasma urealyticum vaginal infections, and moderate expression in cases of Enterobacteriaceae infections, except for Klebsiella; the cases with Klebsiella and Candida species (spp.) vaginitis exhibited a lower expression compared to the healthy control group. VDR, CD44, and OPN had increased placental expression in GBS and Ureaplasma urealyticum vaginal infections; the opportunistic pathogenicity of both Escherichia coli and Candida spp. explains their low IHC positivity, and the tremendous ability of Gram-negative bacteria to elude the host immunity is revealed by the negative IHC staining in cases of Klebsiella vaginitis. These findings suggest that pathogen-specific alterations in the expression of these markers may contribute to the differential risk stratification of pregnancy complications and may mitigate the risks of adverse maternal and fetal outcomes. Interventions aiming to modulate these pathways might improve pregnancy outcomes. Full article

Background: Bronchopulmonary dysplasia (BPD) is a major complication among preterm infants, and nutrition plays a crucial role in its prevention and management. While the nutritional superiority of human milk over preterm formula is well documented, comparisons of the protective benefits of mother’s own milk (MOM) versus donor human milk (DHM) in preterm infants are lacking. We aim to investigate if and how the use of MOM or DHM at the initiation of enteral feeding influences the development of BPD and other respiratory outcomes. Methods: This study evaluated the incidence of BPD and other prematurity outcomes in a cohort of 159 very preterm infants (≤32 weeks GA) who commenced enteral feeding with either MOM or DHM. Results: Enteral feeding was initiated with MOM in 75.5% of the infants and DHM in 24.5%. The incidence of BPD was 24.8% (39 infants), and 10.4% (16 infants) developed moderate-to-severe BPD. Univariate and multivariate analyses revealed no significant differences between the MOM and DHM groups in the rates of BPD, other respiratory outcomes, or key prematurity-related morbidities. Conclusions: Despite the unique bioactive properties of MOM, these findings suggest that DHM is a valid alternative that does not significantly increase the incidence of BPD or other clinical outcomes. Further studies are required to determine the relative contributions of milk volumes and feeding practices to the observed findings. Full article

Introduction: This study aims to examine the relationship between hypoglycemia and general movement patterns during the early post-term-aged in moderate-to-late preterm infants and to assess the interobserver reliability of movement evaluation during this period. Compared with full-term infants, moderate-to-late preterm infants constitute the largest group of premature births globally and are at greater risk of developing neurodevelopmental disorders. Hypoglycemia is one of the most prevalent risk factors in this group. Methods: This prospective single-center explorative cohort study included moderate-to-late preterm infants during their admission in the neonatal intensive care unit. General movements were assessed via Prechtl’s General Movements Assessment, and blood glucose levels were monitored via the FreeStyle Optium™ Neo glucometer. Associations were analyzed via Fisher’s exact test, whereas interobserver reliability was evaluated via the intraclass correlation coefficient (ICC) and the kappa coefficient. Results: A total of 17 moderate-to-late preterm infants with hypoglycemia (<45 mg/dL) presented a relatively high percentage (58.8%) of poor repertoire and normal (35.2%) general movement patterns during the early post-term-aged. Interobserver reliability was good (ICC = 0.7), and the kappa coefficient indicated moderate reliability (0.4). Conclusions: Moderate-to-late preterm infants with transient hypoglycemia may frequently display poor repertoire movement patterns, highlighting the need for careful monitoring. Furthermore, the evaluation of general movements proves to be a reliable tool during the early post-term-aged. Full article