Search

This study aimed to analyze the determinants of neonatal mortality over the last decade (2013–2023), identifying key factors that have influenced neonatal outcomes both before and during the COVID-19 pandemic. Utilizing a systematic literature review approach guided by the PRISMA method, this study evaluates 91 papers collected from indexed databases such as Scopus, PubMed, and Web of Science. The review encompasses studies conducted globally, offering insights into the evolution of neonatal mortality research and the impact of the COVID-19 crisis on neonatal health. The analysis revealed a complex array of risk determinants, categorized into socioeconomic factors, clinical factors, and healthcare access and quality. Notable factors include rural versus urban healthcare disparities, prenatal and postnatal care quality, and the influence of healthcare infrastructure on neonatal outcomes. This study highlights the shifting focus of neonatal mortality research in response to global health challenges, including the pandemic. The findings underscore the need for multidisciplinary approaches to address neonatal mortality, emphasizing the importance of enhancing healthcare systems, improving maternal education, and ensuring equitable access to quality care. Future research should explore the long-term effects of the COVID-19 pandemic on neonatal health and investigate the efficacy of interventions in diverse healthcare settings.

In this case report, we described a rare complication—lung torsion after esophageal atresia repair in a newborn. Torsion of the lung is a critical condition in which either the entire lung or a lung lobe twists, leading to occlusion of blood vessels and airways. The patient’s clinical condition was poor after the primary operation. An emergency thoracotomy showed 180° torsion of the right upper lobe (RUL) and right middle lobe (RML). After detorsion, perioperatively, the lung was gradually reperfused and had a normal appearance. After surgery, the patient was unstable, which culminated in a fatal end (bradycardia, reperfusion injury). Immediate intervention can preserve the affected lung or lung lobe. However, pulmonary torsion typically has a poor prognosis due to misdiagnosis and delayed treatment. Additionally, diagnosis in the neonatal period is even more challenging because the clinical symptoms are nonspecific. In any case, the question is whether detorsion is the right solution or whether a segmentectomy is necessary.

Background/Objectives: Retinopathy of Prematurity (ROP) remains a leading cause of vision impairment in premature infants, especially those with Respiratory Distress Syndrome (RDS) necessitating respiratory support. This study aimed to identify correlations between plasma levels of Insulin-like Growth Factor 1 (IGF1) and Tumor Necrosis Factor-alpha (TNF-alpha), and the risk of developing ROP. Additionally, it explored the association of ROP severity grades with plasma levels of glucose, lactate dehydrogenase (LDH), creatin phosphokinase (CPK), and other biomarkers, aiming to uncover predictive markers for ROP risk and severity in this population. Methods: This prospective study included premature neonates admitted with RDS requiring respiratory support, conducted over 18 months at the Neonatal Intensive Care Unit of the Louis Turcanu Emergency Clinical Hospital for Children, Timisoara. Plasma levels of IGF1 and TNF-alpha were measured on days 1 and 14 post-birth, alongside the initial assessment of glucose, LDH, and CPK levels. Results: Significant correlations were observed between lower gestational age and elevated LDH levels on day 7–10 (rho = −0.341, p = 0.0123) and between TNF-alpha levels at 2 weeks and ROP severity (rho = 0.512, p = 0.0004). Elevated IGF1 levels were protective against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second, suggesting their potential as biomarkers for ROP risk assessment. Higher levels of TNF-alpha at 2 weeks were associated with an increased risk of ROP (Beta = −0.45, p = 0.0014), whereas higher IGF1 levels offered protective effects against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second. Elevated LDH levels on day 7–10 post-birth were linked to an increased risk of ROP (Beta = 0.29, p = 0.0214). Conclusions: These findings highlight the potential of IGF1 and TNF-alpha as predictive biomarkers for ROP, offering avenues for early intervention and improved management strategies in this high-risk group.

Background: Parents play a crucial role in the care of infants during their stay in the neonatal intensive care unit (NICU). Recent studies have reported a decrease in parental participation due to the coronavirus disease (COVID-19) pandemic, which has led to restricted access policies in hospitals. The aim of this study was to describe the barriers to good parental participation during their stay in the neonatal intensive care unit in the COVID-19 era. Methods: This was a quantitative, observational study. Results: A total of 270 parents participated in this study. Mothers’ participation in care was higher than that of fathers (p = 0.017). Parents who lived at the birth of their first child reported a better level of participation in care compared to those who lived at the birth of their second-born (p = 0.005). Parents of extremely preterm neonates reported a lower interaction with their infants than parents of term newborns (p < 0.001). Conclusions: Some disadvantaged categories reported lower scores for cultural and linguistic minorities, parents of multiple children, and fathers. The COVID-19 pandemic has made several family-centred care activities impossible, with a higher impact on those who benefited most of these facilities. This study was prospectively approved by the IRB-CRRM of the University “G. d’Annunzio” Chieti-Pescara on 23 January 2024 (approval number CRRM: 2023_12_07_01).

Leptin is secreted by adipose tissue and expressed in several organs, including the placenta. We investigated the influence of leptin in maternal blood on leptin expression and concentration in the placenta and umbilical cord and its influence on fetal weight and conditions at the time of birth. Twenty-five parturients were recruited, and after childbirth, placental tissue fragments, umbilical arteries, and vein blood were collected. According to leptin concentration in maternal peripheral blood, parturients were divided into low and high leptin groups. Mothers in the high-leptin group had higher age, pre-pregnancy weight, pre-pregnancy BMI, and weight in late pregnancy than mothers in the low-leptin group. Children of mothers in the high-leptin group presented an Apgar score modestly lower than those of the low-leptin group. No differences were observed in leptin concentrations in the umbilical artery and vein. However, the leptin retained in the fetus increased in the high-leptin group compared to the low-leptin group. We observed a negative correlation between fetal leptin retained and maternal age in the low-leptin group. In the high-leptin group, placental leptin concentration was positively correlated with maternal weight in late pregnancy. Nonetheless, the expression of the leptin receptor (Ob-Rb) was negatively correlated with newborn length. In conclusion, this study found a positive correlation between maternal leptin levels and maternal pre-pregnancy weight, BMI, and fetal birth weight. These findings suggest a potential role of leptin in maternal weight regulation during pregnancy and fetal growth.

Background: Umbilical venous catheters (UVCs) are the standard of care in neonatal intensive care units (NICUs) to administer fluids, parenteral nutrition and medications, although complications may occur, including central line-associated blood stream infections (CLABSIs). However, the dwell time to reduce CLABSI risk remains an open issue. Methods: We performed a single-center retrospective study of newborns hospitalized in the Modena NICU with at least one UVC inserted over a 6-year period (period 1: January 2011–December 2013; period 2: January 2019–December 2021). We selected a non-consecutive 6-year period to emphasize the differences in UVC management practices that have occurred over time in our NICU. The UVC dwell time and catheter-related complications during the first 4 weeks of life were examined. Results: The UVC dwell time was shorter in period 2 (median 4 days vs. 5 days, p < 0.00001). Between the two periods, the incidence of CLABSIs remained unchanged (p = 0.5425). However, in period 2, there was an increased need for peripherally inserted central catheters (PICCs) after UVC removal, with a rise in PICC infections after UVC removal (p = 0.0239). Conclusions: In our NICU, shortening UVC dwell time from 5 to 4 days did not decrease the UVC-related complications. Instead, the earlier removal of UVCs led to a higher number of PICCs inserted, possibly increasing the overall infectious risk.

Candida spp. is rarely found in neonatal early-onset sepsis (EOS) etiology. However, candidemia is associated with increased mortality and morbidity, as in late-onset sepsis. Congenital candidiasis may present as a mucocutaneous infection or, more rarely, as a systemic infection in term and preterm infants. This paper presents case reports of two cases of congenital systemic candidiasis (CSC) caused by Candida albicans and a review of the data in the literature. An electronic search of PubMed, Scopus, and Google Scholar was performed to identify publications on congenital candidiasis. Both neonates were male, born vaginally, with risk factors for congenital candidiasis. One of the infants was born at term and presented with an almost generalized maculopapular rash at birth and congenital candidemia; parenteral fluconazole was used successfully. The other infant was born prematurely at 28 weeks of gestation; blood culture, gastric aspirate, and maternal vaginal cultures sampled at birth were positive for C. albicans. Liver and kidney involvement became apparent on the third day of life, while lung involvement was clinically evident on the fourth day. Prolonged parenteral fluconazole was administered due to multiple organ involvement and persistent candidemia. Our experience with the presented cases, similar to data in the literature, suggests that CSC may occur at any gestational age, with various clinical pictures, sometimes mimicking bacterial sepsis, and even in the absence of the rash. Careful anamnesis and a high index of suspicion are important for the prompt recognition and treatment of CSC, optimizing the short- and long-term outcomes. Further research should focus on CSC to improve its diagnosis.

Background: The prevalence of overweight (OW), obesity (OB), and gestational diabetes mellitus (GDM) has been increasing worldwide in recent years. Adipolin is a new adipokine with reduced circulating levels in obesity and type 2 diabetes mellitus (T2DM). Objectives: Our prospective case-control study aimed to evaluate the maternal serum levels of adipolin and adiponectin, metabolic parameters, and anthropometric characteristics at the time of oral glucose tolerance test (OGTT) in pregnant women with a pre-pregnancy body mass index (BMI) ≥ 25 Kg/m2 and correlate them with newborn adipolin, adiponectin levels, and anthropometric characteristics of the newborns, and secondly to evaluate pregnancy outcomes. Material and Methods: After the OGTT results, we had 44 OW/OB pregnant women with GDM, 30 OW/OB pregnant women without GDM, and 92 lean healthy (LH) pregnant women. Data were analyzed by ANOVA and correlation tests, with a p-value < 0.05 considered significant. Results: We found no differences between adipolin values of the OW/OB pregnant women with GDM and the LH group (p > 0.99), OW/OB without GDM and the LH group (p = 0.56), and between OW/OB groups (p = 0.57). OW/OB pregnant women with GDM had a higher rate of gestational hypertension compared with the LH group (p < 0.0001). Newborns from OW/OB pregnant women with GDM were more frequently diagnosed with jaundice (p = 0.02), and they required more frequent admission to the neonatal intensive care unit (NICU) for treatment of respiratory distress (p = 0.01) compared with newborns from LH mothers. Conclusions: Our study revealed that the serum levels of adipolin in the second trimester among the group of OW/OB pregnant women with GDM, matched for age and BMI with OW/OB pregnant women without GDM, were not significantly different. This suggests that adipolin may not play an essential role in the occurrence of GDM in these patients. Despite good glycemic control during pregnancy, OW/OB pregnant women with GDM and their newborns tend to have more complications (gestational hypertension, jaundice, NICU admission) than LH pregnant women and their newborns, highlighting the importance of weight control before pregnancy.

Isolated musculoskeletal infantile myofibroma is a rare tumor of pediatric age. The majority of cases are seen in children under two years old, but it can occur at any age as a painless enlarging mass that involves bone, skin, or soft tissue, typically accompanied by compression symptoms. Perineural involvement is extremely rare in myofibromas. Neurological impairment can occur during infancy but isolated nerve palsy, particularly in peripheral nerves within the upper extremity, is very uncommon. Neonatal radial nerve palsy is a rare entity caused by different conditions. Among these, we mention local tumors affecting peripheral nerves, such as myofibroma. There are few cases described in the literature, which mainly concern adult patients. The authors present a case of congenital isolated radial nerve palsy in a newborn with MF of the right elbow, which resulted in impairment of the wrist and finger extension. Following a six-month monitoring period, the patient underwent surgical treatment to restore function to his right wrist and hand. This involved excising the infiltrated radial nerve segment associated with palliative surgery. Despite the benignity of this lesion, severe nerve damage and perineural involvement may require surgical treatment with nerve resection and reconstruction.

Background: Children who are exposed to HIV in utero but are uninfected (HIV-exposed uninfected or HEU) are at higher risk of neurodevelopmental delays compared to children born to persons without HIV. Magnetic resonance imaging (MRI) studies have revealed differences in grey matter volumes, cerebral perfusion, and white matter changes in these children. However, MRI is costly and not widely available in areas with high HIV prevalence, like Botswana, where more than 15% of children are HEU. To address this, we explored the use of brain ultrasound, conducted by trained study nurses, as a safe, less costly, and accurate alternative method for assessing differences relating to HIV exposure status in the brain structures of neonates. Methods: Brain ultrasounds of newborns in the Following Longitudinal Outcomes to Understand, Report, Intervene and Sustain Health for Infants, Children, Adolescents who are HIV Exposed Uninfected (FLOURISH) observational study—comprising 35 HEU newborns and 24 HIV-unexposed (HU) newborns—were performed by study nurses and evaluated by a pediatric radiologist for quality and structural abnormalities, such as calcifications, cysts, and hemorrhages. Two radiologists measured extra-axial cerebrospinal fluid spaces, ventricles, and the corpus callosum. Results: Ultrasound studies of 59 newborns (59% boys; median gestational age 38.4 weeks) were completed. All studies were of diagnostic quality, with 90.2% rated as being of good or excellent quality. Structural abnormalities were rare (10.2% incidence) and did not differ by HIV exposure group. Corpus callosum length was shorter in HEU infants compared to HU infants (45.7 mm vs. 47.3 mm; p = 0.03). Other ventricular and corpus callosum measurements showed no significant variations. Conclusions: Brain ultrasounds conducted by study nurses are feasible and reveal differences in corpus callosum length between HEU and HU infants. The benefits of easier training, lower cost, and rapid deployment make ultrasound a promising screening tool in resource-limited settings.

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case–control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at −80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes’ degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP.

Sex chromosome aneuploidies (SCAs) collectively occur in 1 in 500 livebirths, and diagnoses in the neonatal period are increasing with advancements in prenatal and early genetic testing. Inevitably, SCA will be identified on either routine prenatal or newborn screening in the near future. Tetrasomy SCAs are rare, manifesting more significant phenotypes compared to trisomies. Prenatal cell-free DNA (cfDNA) screening has been demonstrated to have relatively poor positive predictive values (PPV) in SCAs, directing genetic counseling discussions towards false-positive likelihood rather than thoroughly addressing all possible outcomes and phenotypes, respectively. The eXtraordinarY Babies study is a natural history study of children prenatally identified with SCAs, and it developed a longitudinal data resource and common data elements with the Newborn Screening Translational Research Network (NBSTRN). A review of cfDNA and diagnostic reports from participants identified a higher than anticipated rate of discordance. The aims of this project are to (1) compare our findings to outcomes from a regional clinical cytogenetic laboratory and (2) describe discordant outcomes from both samples. Twenty-one (10%), and seven (8.3%) cases were found to be discordant between cfDNA (result or indication reported to lab) and diagnosis for the Babies Study and regional laboratory, respectively. Discordant results represented six distinct discordance categories when comparing cfDNA to diagnostic results, with the largest groups being Trisomy cfDNA vs. Tetrasomy diagnosis (66.7% of discordance in eXtraordinarY Babies study) and Mosaicism (57.1% in regional laboratory). Traditional genetic counseling for SCA-related cfDNA results is inadequate given a high degree of discordance that jeopardizes the accuracy of the information discussed and informed decision making following prenatal genetic counseling.

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). Targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, the inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference < 10th centile, failed hearing screen, and prematurity. During the first three years of use of this program (2021–2023), 940 (12.3%) of 7651 live-born infants were tested. The most common indication was birthweight < 10th centile (n = 633, 67.3%). Eleven neonates were diagnosed as congenitally infected, for a prevalence of 1.17% (95%CI 0.48–1.86) on tested neonates and of 0.14% (95%CI 0.06–0.23) on live-born infants. None of the cCMV-infected newborns had a failed hearing screen as a testing indication. Implementation of an expanded cCMV screening program appears feasible and of clinical value.

Background: Nasal high-frequency oscillatory ventilation (nHFOV) has emerged as an effective initial and rescue noninvasive respiratory support mode for preterm infants with respiratory distress syndrome (RDS); however, little is known about nHFOV use in Romanian neonatal intensive care units (NICUs). Objectives: We aimed to identify the usage extent and clinical application of nHFOV in Romania. Methods: A structured web-based questionnaire was designed to find the rate of nHFOV use and knowledge of this new method of noninvasive respiratory support in Romanian level III NICUs. Using multiple-choice, open-ended, and yes/no questions, we collected information on the NICU’s size, noninvasive respiratory support modes used, nHFOV use, indications, settings, nasal interfaces, secondary effects, and equipment used. Descriptive statistics and comparisons were performed using IBM SPSS Statistics 26.0. Results: A total of 21/23 (91.3%) leaders from level III NICUs (median [IQR] number of beds of 10 [10–17.5]) responded to the survey. The most frequently used noninvasive ventilation modes were CPAP mode on mechanical ventilators (76.2%), followed by NIPPV (76.2%); heated, humidified high-flow nasal cannula (HHHFNC) (61.9%); and nHFOV (11/21 units; 52.4%). A total of 5/11 units reported frequent nHFOV use (in two or more newborns/month) in both term and preterm infants. The main indications reported for nHFOV use were CPAP failure (90.9%), hypercapnia (81.8%), and bronchopulmonary dysplasia (72.7%). Face/nasal masks and short binasal prongs are the most commonly used nasal interfaces (90.9% and 72.7%, respectively). Air leaks at the interface level (90.9%), thick secretions (81.8%), and airway obstruction (63.6%) were the most frequently mentioned adverse effects of nHFOV. Only three of the NICUs had a written protocol for nHFOV use. Most units not yet using nHFOV cited lack of equipment, experience, training, or insufficient information and evidence for the clinical use and outcome of nHFOV use in neonates as the main reasons for not implementing this noninvasive respiratory mode. Conclusions: Our survey showed that nHFOV is already used in more than half of the Romanian level III NICUs to support term and preterm infants with respiratory distress despite a lack of consensus regarding indications and settings during nHFOV.

Background: Healthcare providers (HCPs) working in labour and delivery rooms need to undergo regular refresher courses to maintain their neonatal resuscitation skills, which are shown to decline over time. However, due to their irregular schedules and limited time, HCPs encounter difficulties in readily accessing refresher programs. RETAIN is a digital game that simulates a delivery room to facilitate neonatal resuscitation training for HCPs. Objective: This study aims to ascertain whether participants enjoyed the RETAIN digital game simulator and whether it was at least as good as a video lecture at refreshing and maintaining participants’ neonatal resuscitation knowledge. Methods: In this randomized controlled simulation trial, n = 42 labour and delivery room HCPs were administered a pre-test of neonatal resuscitation knowledge using a manikin. Then, they were randomly assigned to a control or a treatment group. For 20–30 min, participants in the control group watched a neonatal resuscitation lecture video, while those in the treatment group played the RETAIN digital game simulator of neonatal resuscitation scenarios. Then, all participants were administered a post-test identical to the pre-test. Additionally, participants in the treatment group completed a survey of attitudes toward the RETAIN simulator that provided a measure of enjoyment of the RETAIN game simulator. After two months, participants were administered another post-test identical to the pre-test. Results: For the primary outcome (neonatal resuscitation performance), an analysis of variance revealed that participants significantly improved their neonatal resuscitation performance over the first two time points, with a significant decline to the third time point, the same pattern of results across conditions, and no differences between conditions. For the secondary outcome (attitudes toward RETAIN), participants in the treatment condition also reported favourable attitudes toward RETAIN. Conclusions: Labour and delivery room healthcare providers in both groups (RETAIN simulator or video lecture) significantly improved their neonatal resuscitation performance immediately following the intervention, with no group differences. The findings suggest that participants enjoyed interacting with the RETAIN digital game simulator, which provided a similar boost in performance right after use to the more traditional intervention.

Background: Therapeutic hypothermia is the standard treatment for neonates with hypoxic–ischemic encephalopathy. Preclinical evidence indicates that the time to initiate therapeutic hypothermia correlates with its therapeutic success. This study aims to explore whether there is a correlation between the early initiation of therapeutic hypothermia and improved short-term neurological outcomes in cooled asphyxiated newborns. Methods: A retrospective analysis was conducted, involving 68 neonates from two different neonatal intensive care units. The impact of time to initiate treatment, time to reach the target temperature, and time between initiation and target temperature was correlated with short-term outcomes on MRI. Results: We did not find a significant difference between outcomes regarding the time to start treatment and the time to achieve the target temperature. Interestingly, neonates with a poor outcome were treated on average earlier than neonates with a favorable outcome but required more time to reach the target temperature. Additionally, the study results did not support the hypothesis that a shorter time to initiate treatment would lead to shorter times to achieve the target temperature. Conclusion: Based on our findings, it is recommended to prioritize a thorough evaluation of neonatal encephalopathy before initiating therapeutic hypothermia. Early initiation of treatment should be balanced with the time required for precise assessment to ensure better outcomes.

Background: We analyzed the impact of social distancing (SD) on vitamin D status and associated morbidity in neonates during the coronavirus disease (COVID-19) pandemic. Methods: Serum levels of 25-hydroxy vitamin D (25OHD) and clinical characteristics of newborn infants before (2019) and during SD (2021) were compared. Results: A total of 526 neonates (263 in 2019 and 263 in 2021) were included. The rate of vitamin D deficiency in neonates (47.1% vs. 35.4 %, p = 0.008) decreased and the rate of maternal vitamin D intake increased (6.8% vs. 37.6%, p < 0.001), respectively, during SD compared to those in 2019. The rates of hypocalcemia (12.5% vs. 3.8%, p < 0.001) and respiratory illness (57.0% vs. 43.0%, p = 0.002) decreased during SD. Neonatal vitamin D deficiency during SD was associated with maternal vitamin D supplementation (odds ratio [OR] = 0.463, p = 0.003) but was not associated with SD (OR = 0.772, p = 0.189). The mediation effect of SD on neonatal morbidity by neonatal vitamin D status was statistically insignificant. Conclusions: SD might affect the increased maternal vitamin D intake and decreased neonatal vitamin D deficiency. However, neonatal morbidity was not affected by SD, even with neonatal vitamin D status changes.

During the last decades, endocrine-disrupting chemicals (EDCs) have attracted the attention of the scientific community, as a result of a deepened understanding of their effects on human health. These compounds, which can reach populations through the food chain and a number of daily life products, are known to modify the activity of the endocrine system. Regarding vulnerable groups like pregnant mothers, the potential damage they can cause increases their importance, since it is the health of two lives that is at risk. EDCs can affect the gestation process, altering fetal development, and eventually inducing the appearance of many disorders in their childhood and/or adulthood. Because of this, several of these substances have been studied to clarify the influence of their prenatal exposure on the cognitive and psychomotor development of the newborn, together with the appearance of non-communicable diseases and other disorders. The most novel research on the subject has been gathered in this narrative review, with the aim of clarifying the current knowledge on the subject. EDCs have shown, through different studies involving both animal and human investigation, a detrimental effect on the development of children exposed to the during pregnancy, sometimes with sex-specific outcomes. However, some other studies have failed to find these associations, which highlights the need for deeper and more rigorous research, that will provide an even more solid foundation for the establishment of policies against the extended use of these chemicals.

The nutrition of preterm infants remains contaminated by wrong beliefs that reflect inexactitudes and perpetuate old practices. In this narrative review, we report current evidence in preterm neonates and in preterm neonates undergoing surgery. Convictions that necrotizing enterocolitis is reduced by the delay in introducing enteral feeding, a slow advancement in enteral feeds, and the systematic control of residual gastric volumes, should be abandoned. On the contrary, these practices prolong the time to reach full enteral feeding. The length of parenteral nutrition should be as short as possible to reduce the infectious risk. Intrauterine growth restriction, hemodynamic and respiratory instability, and patent ductus arteriosus should be considered in advancing enteral feeds, but they must not translate into prolonged fasting, which can be equally dangerous. Clinicians should also keep in mind the risk of refeeding syndrome in case of high amino acid intake and inadequate electrolyte supply, closely monitoring them. Conversely, when preterm infants undergo surgery, nutritional strategies are still based on retrospective studies and opinions rather than on randomized controlled trials. Finally, this review also highlights how the use of adequately fortified human milk is strongly recommended, as it offers unique benefits for immune and gastrointestinal health and neurodevelopmental outcomes.

Preterm infants have increased body adiposity at term-equivalent age and risk of adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low-birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with p < 0.001); lean mass did not differ. None of the nutrients had any impact on BC of EP infants. Protein intake did not result in a higher lean mass in either group; fat intake was a significant predictor of increased fat mass percentage in VP infants at discharge (p = 0.007) and body adiposity at 12 months of CA (p = 0.021). Nutritional needs may depend on gestational age and routine fortification should be used with caution in more mature infants.

Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70–75% of women at least once in their lives. During pregnancy, the prevalence of VVC is estimated to be around 20%, peaking at about 30% in the third trimester, with a number of specific risk factors predisposing to yeast infection being identified and needing elucidation. This review aims to provide updated knowledge on candidiasis during pregnancy, addressing risk factors and maternal and neonatal outcomes, as well as discussing optimal therapeutic strategies to safeguard mothers and newborns. The bibliographic search involved two biomedical databases, PubMed and Embase, without imposing time limits. Among all Candida spp., Candida albicans remains the most frequent causative species. The hyperestrogenic environment of the vaginal mucosa and reduced immune defenses, physiological effects of pregnancy, create conditions favorable for Candida spp. vaginal colonization and hence VVC. Recent evidence shows an association between VVC and adverse obstetric outcomes, including premature membrane rupture (PROM), chorioamnionitis, preterm birth, and puerperal infections. Prompt and effective management of this condition is therefore crucial to prevent adverse obstetric outcomes, maternal–fetal transmission, and neonatal disease. Additional studies are required to confirm the benefits of systemic treatment for maternal candida infection or colonization in preventing premature birth or neonatal systemic candidiasis.

(1) Background: This study aimed to determine whether standard-dose vitamin D supplementation could provide adequate levels in exclusively breastfed infants born with different cord 25(OH)D levels and to evaluate related neonatal morbidities. (2) Methods: A prospective cross-sectional study was designed in term infants. Three groups were formed based on cord 25(OH)D levels; Group1 Deficiency:25(OH)D < 12 ng/mL, Group2 Insufficiency:25(OH)D = 12–19 ng/mL, and Group3 Optimum:25(OH)D = 20–100 ng/mL. Cord and 1st month 25(OH)D levels, after receiving standard-dose vitamin D prophylaxis, neonatal outcomes and anthropometric measurements were compared. (3) Results: The study involved 86 infants. Group1 Deficiency had also significantly lower 25(OH)D levels at 1st month compared to the others (p < 0.001). There was a significant positive correlation between cord and 1st month 25(OH)D levels (r = 0.78, p < 0.001). Despite the fact that the mother’s age and clothing style were similar, Group1 Deficiency mothers had higher parity numbers and used less vitamin D during pregnancy (p = 0.03, p = 0.04). Neonatal outcomes analysis revealed that newborns in Group1 Deficiency experienced more respiratory distress, transient tachypnea, and early-onset sepsis, as well as more and longer hospital stays in the first-month of life (p < 0.05). (4) Conclusions: Infants with low cord 25(OH)D levels had also lower 25(OH)D values in the 1st month of life and experienced higher rates of neonatal morbidities. Given its numerous biological activities and impact on neonatal morbidities, determining an individualized dose of vitamin D supplementation may be more accurate than using the standard approach.

The aim of this study was to develop and validate a predictive model for the establishment of skin-to-skin contact immediately after birth. A descriptive cross-sectional study was conducted during the last trimester of 2022 and the first trimester of 2023 with women who had given birth in Spain. A questionnaire containing sociodemographic, psychosocial, and health variables referring to the mother and the newborn, as well as the Bond and Attachment questionnaire (VAMF, for its name in Spanish) for the analysis of the mother–child bond and attachment, were administered. A multivariate analysis was performed, and areas under the ROC curve (AUC) with their 95% confidence intervals (CI) and the predictive characteristics of these models were estimated. In total, 1077 women participated. The prevalence of early skin-to-skin contact after delivery was 50.2% (468) in the derivation cohort and 49.8% (464) in the validation cohort. Multivariate analysis showed that prematurity, type of delivery, and birth experience were statistically significant, so they were included in the model (p ≤ 0.05). The predictive ability (AUC ROC) was good in both the derivation cohort, yielding 0.92 (95% CI: 0.89–0.95), and in the validation cohort, yielding 0.89 (95% CI: 0.85–0.93). This study developed a predictive model identifying factors facilitating early skin-to-skin contact between a mother and her newborn immediately after birth.

Early-onset sepsis (EOS) is a rare but profoundly serious bacterial infection. Neonates at risk of EOS are often treated with antibiotics. The start of empiric antibiotic therapy can successfully be reduced by the implementation of the EOS calculator. However, once started, antibiotic therapy is often continued despite a negative blood culture. To decrease the burden of antibiotic therapy, it is necessary to know whether the clinician’s reasons are based on objective factors. Therefore, we performed a retrospective single-centre cohort study to identify the factors associated with prolongation of antibiotic therapy in neonates with suspected EOS but a negative blood culture. Maternal, clinical, and laboratory data of neonates with a gestational age of ≥32 weeks, admitted between January 2019 and June 2021, were collected. Among neonates with a negative blood culture, we compared neonates with prolonged (≥3 days) to neonates with discontinued (

Enteroviruses (EVs) are the most common causes of viral myocarditis in neonates. Neonatal enterovirus myocarditis manifestations range from nonspecific febrile illness to congestive heart failure and cardiogenic shock with high risk of in-hospital mortality and long-term cardiac sequelae. Early recognition is essential to undertake appropriate therapy and predict outcomes. Echocardiography and echo-derived left ventricular strain measures seem promising for these purposes. We herein report two cases of neonatal enterovirus-associated myocarditis in dichorionic diamniotic twins, with different presentation, clinical course, and intensity of treatments.

In newborns, white matter shows a high T2-weighted (T2w) signal in MRI with poor grey–white matter contrast. To increase this contrast, an extremely long echo time (TE) is used in the examination of children. It is not known up to what age this long TE should be used. The purpose of this study was to find up to what age a long TE should be used in infants. In the prospective study, 101 infants (0–18 months) underwent cranial MRI at 3 Tesla. T2-weighted Fast Spin Echo sequences with long TE (200 ms) and medium TE (100 ms) were used. The signal intensities of the cortex and white matter were measured and the grey–white matter contrast (MC) was calculated. A cut-off age was determined. The T2w sequences with long TE had a statistically significantly higher MC until the age of six months (medium TE: 0.1 ± 0.05, Long TE: 0.19 ± 0.07; p < 0.001). After the tenth month, the T2w sequence with medium TE provided significantly better MC (Medium TE: 0.1 ± 0.05; long TE: 0.05 ± 0.4; p < 0.001). The use of a long TE is only helpful in the first six months of life. After the tenth month of life, a medium TE should be favored as is used in adult brain MRI.

Supraglottic airway devices such as laryngeal masks and i-gels are useful for airway management. The i-gel is a relatively new device that replaces the air-inflated cuff of the laryngeal mask with a gel-filled cuff. It remains unclear which device is more effective for neonatal resuscitation. We aimed to evaluate the dependence of successful airway management in neonatal simulators on the device type and providers’ backgrounds. Ninety-one healthcare providers performed four attempts at airway management using a laryngeal mask and i-gel in two types of neonatal manikins. The dependence of successful insertions within 16.7 s (75th percentile of all successful insertions) on the device type and providers’ specialty, years of healthcare service, and completion of the neonatal resuscitation training course was assessed. Successful insertion (p = 0.001) and insertion time (p = 0.003) were associated with using the i-gel vs. laryngeal mask. The providers’ backgrounds were not associated with the outcome. Using the i-gel was associated with more successful airway management than laryngeal masks using neonatal manikins. Considering the limited effect of the provider’s specialty and experience, using the i-gel as the first-choice device in neonatal resuscitation may be advantageous. Prospective studies are warranted to compare these devices in the clinical setting.

A number of studies have demonstrated the role of sex in regulating immune responses to vaccination. However, these findings have been limited to adults for both human and animal models. As a result, our understanding of the impact of sex on vaccine responses in the newborn is highly limited. Here, we probe this important question using a newborn non-human primate model. We leveraged our prior analysis of two cohorts of newborns, with one being mother-reared and one nursery-reared. This provided adequate numbers of males and females to interrogate the impact of sex on the response to inactivated influenza vaccines alone or adjuvanted with R848, flagellin, or both. We found that, in contrast to what has been reported in adults, the non-adjuvanted inactivated influenza virus vaccine induced similar levels of virus-specific IgG in male and female newborns. However, the inclusion of R848, either alone or in combination with flagellin, resulted in higher antibody titers in females compared to males. Sex-specific increases in the neutralizing antibody were only observed when both R848 and flagellin were present. These data, generated in the highly translational NHP newborn model, provide novel insights into the role of sex in the immune response of newborns.

We developed a new neonatal neuromotor test battery, the Neonatal Infant Motor Assessment Scale (NIMAS), to perform a detailed neuromotor and holistic assessment of at-risk infants in the neonatal period. Methods: A total of 68 infants (28–41 Gestational weeks) hospitalised in the Neonatal Intensive Care Unit were included in the study. The NIMAS is a scale consisting of Automatic Motor Area, Functional Motor Area and sociodemographic form. The Dubowitz Neurological Examination and the Amiel-Tison Neurological Assessment Tests were also applied to evaluate the construct validity of the test. Results: The mean gestational age at birth was 34.62 ± 3.07 weeks and birth weight was 2305.66 ± 738.95. Fifty-one (75%) of the babies were premature and 17 (25%) were term babies. The KMO value to test the adequacy of the distribution for factor analysis was found to be at a very good level. Barlett’s test result was 2198.389 (p < 0.05). The amount of variance obtained as 44.76% in the study was at a sufficient level. The factor loads of the questions in the automatic motor domain dimension varied between 0.523 and 0.694 and the factor loads of the questions in the functional motor domain dimension varied between 0.619 and 0.772. Since Cronbach’s alpha was above 0.70, the reliability was adequate. Inter-rater scale agreement in the automatic motor domain was 81.1%; scale agreement in the functional motor domFain was 92.9%; and the NIMAS total score agreement was 93.4%. These agreements were statistically significant (p < 0.05). Total correlation above 0.20 indicates that the item is important for the question. According to the results obtained, total correlation values were between 0.258 and 0.720. Conclusions: The NIMAS is the first test battery to assess the “Functional Motor Area” and this questionnaire, based on the results of the analyses, is a valid, reliable and clinically usable measurement tool for the infant at-risk at the neonatal period.

The ductus arteriosus represents an essential vascular structure connecting the pulmonary artery and the aorta. Over the past decades, there has been substantial advancement in our understanding of both the fundamental and clinical aspects of the ductus arteriosus. In particular, the clarification of the regulatory mechanisms governing ductal patency in critical stages such as the fetal and the perinatal period has enabled optimal management of both physiological and pathological conditions in which the ductus arteriosus plays a crucial role. Furthermore, a more in-depth understanding of the regulatory mechanisms controlling this fundamental structure has facilitated the development of advanced therapeutic strategies and personalized interventions. In the present review, we provide a comprehensive overview of the ductus arteriosus during fetal and perinatal life, encompassing its physiological functions, pathological conditions, and clinical implications. Through this examination, we aim to contribute to a broader understanding of the ductus arteriosus’ role in these critical developmental stages and its significance in clinical practice.

Mitochondrial DNA (mtDNA) released from dead or injured cells can activate inflammation, and mesenchymal stem cell (MSC) transplantation can reduce inflammation and injury. However, it has not been tested whether the release of mtDNA can be reduced by MSC transplantation. We hypothesized that the level of extracellular mtDNA would be increased after hyperoxia-induced lung injury but reduced after lung injury attenuation by MSC therapy in our newborn rat model. In an in vitro study using a rat lung epithelial L2 cell line, we found that the level of extracellular mtDNA was significantly increased with H2O2-induced cell death but reduced after MSC co-incubation. In an in vivo study, we confirmed that the levels of cell death, extracellular mtDNA, and inflammatory cytokines were significantly increased in hyperoxic newborn rat lungs but reduced after MSC transplantation. The levels of extracellular mtDNA were significantly and positively correlated with the levels of the inflammatory cytokines. The TLR9/MyD88/NF-κB pathway, which is activated by binding to mtDNA, was also significantly upregulated but downregulated after MSC transplantation. We found a significant positive correlation between inflammatory cytokines and extracellular mtDNA in intubated neonates. The levels of inflammatory cytokines and extracellular mtDNA changed over time in a similar pattern in transtracheal aspirate samples from intubated neonates. In conclusion, increased levels of extracellular mtDNA are associated with increased inflammation in hyperoxia-induced lung injury, and attenuation of lung inflammation by MSC therapy is associated with reduced levels of extracellular mtDNA.

Background: Neonates have an increased risk of vitamin D insufficiency due to the inadequate supplementation of mothers and infants after birth. Insufficiency of vitamin D is frequently detected in critically ill patients and is associated with disease severity and mortality. There is yet to be a consensus on the appropriate regimen of vitamin D3 supplementation in high-risk infants. Aim: The main objectives of this study were to determine the prevalence of vitamin D insufficiency in neonates with severe comorbidities and to evaluate whether high-dose vitamin D3 oral administration leads to normal plasmatic concentrations without side effects. Methods: The current study was a randomized, prospective trial of 150 patients admitted to the Neonatal Intensive Care Unit (NICU) at Maria Sklodowska Curie Emergency Children’s Hospital in Bucharest. Patients were divided into three subgroups based on the chronological order of their admission date. Each subgroup received a different pharmaceutical product of vitamin D3. We administered a dosage of 10,000 IU/kg of vitamin D3 orally in three steps, as follows: at admission, one week after admission, and one month from the first administration, targeting a serum 25-hydroxyvitamin D concentration of at least 40 ng/mL. Results: Most neonates (68%) achieved an optimum vitamin D level after one month, even though only 15% of patients had an optimum concentration at admission. After the first high dose of vitamin D3, there was a 27% increase in the mean vitamin D plasmatic level compared to admission levels. However, after one month, the concentrations decreased in all subgroups due to the gap of three weeks between the last two administrations. Conclusions: An intermittent, weekly high-dose vitamin D3 oral administration leads to a steadier increase and normalization of vitamin D concentration in most critically ill neonates. However, high-dose vitamin D3 administered orally after three weeks decreases vitamin D levels in this high-risk population.

Background: Brief Resolved Unexplained Events (BRUEs), formerly known as Apparent Life-Threatening Events (ALTEs), are concerning episodes of short duration (typically p = 0.009). Respiratory symptoms during BRUEs were more frequent during the pandemic (coefficient B = 0.654; p = 0.052). Fever during BRUEs was less likely during the pandemic (coefficient B = −0.465, p = 0.046). Conclusions: These findings could have significant clinical implications for managing children with BRUEs during the COVID-19 pandemic.

Inflammation, oxidative injury, and gut dysbiosis play an important role in the pathogenesis of necrotising enterocolitis (NEC). Plant-derived substances have historically been used as therapeutic agents due to their anti-inflammatory, antioxidant, and antimicrobial properties. We aimed to review pre-clinical evidence for plant-derived substances in the prevention and treatment of NEC. A systematic review was conducted using the following databases: PubMed, EMBASE, EMCARE, MEDLINE and Cochrane Library (PROSPERO CRD42022365477). Randomized controlled trials (RCTs) and quasi-RCTs that evaluated a plant-derived substance as an intervention for NEC in an animal model of the illness and compared pre-stated outcomes (e.g., clinical severity, severity of intestinal injury, mortality, laboratory markers of inflammation and oxidative injury) were included. Sixteen studies (n = 610) were included in the systematic review. Ten of the sixteen included RCTs (Preterm rat pups: 15, Mice: 1) reported mortality and all reported NEC-related histology. Meta-analysis showed decreased mortality [12/134 vs. 27/135; RR: 0.48 (95% CI: 0.26 to 0.87); p = 0.02, 10 RCTs] and decreased NEC in the experimental group [24/126 vs. 55/79; RR: 0.34 (95% CI: 0.22 to 0.52); p < 0.001, 6 RCTs]. Markers of inflammation (n = 11) and oxidative stress (n = 13) improved in all the studies that have reported this outcome. There was no significant publication bias for the outcome of mortality. Plant-derived substances have the potential to reduce the incidence and severity of histologically diagnosed NEC and mortality in rodent models. These findings are helpful in guiding further pre-clinical studies towards developing a food supplement for the prevention of NEC in preterm infants.

Background: There are wide variations in antibiotic use in neonatal intensive care units (NICUs). Limited data are available on antimicrobial stewardship (AS) programs and long-term maintenance of AS interventions in preterm very-low-birth-weight (VLBW) infants. Methods: We extended a single-centre observational study carried out in an Italian NICU. Three periods were compared: I. “baseline” (2011–2012), II. “intervention” (2016–2017), and III. “maintenance” (2020–2021). Intensive training of medical and nursing staff on AS occurred between periods I and II. AS protocols and algorithms were maintained and implemented between periods II and III. Results: There were 111, 119, and 100 VLBW infants in periods I, II, and III, respectively. In the “intervention period”, there was a reduction in antibiotic use, reported as days of antibiotic therapy per 1000 patient days (215 vs. 302, p < 0.01). In the “maintenance period”, the number of culture-proven sepsis increased. Nevertheless, antibiotic exposure of uninfected VLBW infants was lower, while no sepsis-related deaths occurred. Our restriction was mostly directed at shortening antibiotic regimens with a policy of 48 h rule-out sepsis (median days of early empiric antibiotics: 6 vs. 3 vs. 2 in periods I, II, and III, respectively, p < 0.001). Moreover, antibiotics administered for so-called culture-negative sepsis were reduced (22% vs. 11% vs. 6%, p = 0.002), especially in infants with a birth weight between 1000 and 1499 g. Conclusions: AS is feasible in preterm VLBW infants, and antibiotic use can be safely reduced. AS interventions, namely, the shortening of antibiotic courses in uninfected infants, can be sustained over time with periodic clinical audits and daily discussion of antimicrobial therapies among staff members.

Pertussis is an important cause of mortality and morbidity in infancy. It is recommended that close contacts of the baby be vaccinated with Tdap, and this practice is called the cocoon strategy. This study aimed to investigate the applicability of the cocoon strategy and to determine the factors affecting the process. Mothers of babies who were hospitalized in the neonatal intensive care unit were included in the study. In the first stage, a face-to-face questionnaire was given to the mothers to measure their level of knowledge about whooping cough and its vaccine. In the second stage, written and verbal information about the cocoon strategy was given, and then vaccination intentions for Tdap were learned. In the third stage, all mothers were contacted 3 weeks after and asked whether they had received a Tdap vaccination and why. Of these mothers, 68% could not answer any questions about pertussis disease and vaccines correctly. After the information, 35% (n = 78) of the mothers stated that they were considering getting vaccinated, while only 2% (n = 5) of the mothers were able to get the Tdap vaccine. The most important reasons for not getting vaccinated were a lack of time (24%) and the cost of vaccination (23%). It is predicted that Tdap vaccination rates may increase if the cost of vaccine, availability of vaccine, and the access of mothers to the vaccine application are facilitated.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 600 million people worldwide, including millions of pregnant women. While newborns exposed to other viruses in utero are sometimes at high risk for vertical transmission, a substantial body of literature since early 2020 has demonstrated that vertical transmission of SARS-CoV-2 from infected mother to neonate is rare, and that newborns who do become infected with SARS-CoV-2 generally have favorable outcomes. In this review, the authors evaluate the existing literature on vertical transmission of SARS-CoV-2 and its potential mechanisms and discuss short- and long-term health outcomes in newborns who were exposed to SARS-CoV-2 in utero. The authors conclude that vertical transmission and adverse neonatal and infant/child outcomes are unlikely, but that neonates exposed to prenatal maternal SARS-CoV-2 infection may be at slightly higher risk for preterm birth, possibly related to increased risk of severe COVID-19 disease in pregnant women, placental changes, or infection timing. Ultimately, the need for additional and longer-term follow-up data in this population is highlighted.

Adrenal function is essential for survival and well-being of preterm babies. In addition to glucocorticoids, it has been hypothesized that C19-steroids (DHEA-metabolites) from the fetal zone of the adrenal gland may play a role as endogenous neuroprotective steroids. In 39 term-born (≥37 weeks gestational age), 42 preterm (30–36 weeks) and 51 early preterm (k-means clustering). Individual steroidal fingerprints and clinical phenotype were analyzed at the 3rd day of life. Overall, the excretion rates of C21-steroids (glucocorticoid precursors, cortisol, and cortisone metabolites) were low (19-steroids were up to 10 times higher. There was a shift to higher excretion rates of C19-steroids in both preterm groups compared to term infants but only minor differences in the distribution of C21-steroids. Comparable metabolic patterns were found between gestational age groups: Cluster 1 showed mild elevation of C21- and C19-steroids with the highest incidence of neonatal morbidities in term and severe intraventricular hemorrhage in early preterm infants. In cluster 2 lowest excretion in general was noted but no clinically unique phenotype. Cluster 3 showed highest elevation of C21-steroids and C19-steroids but no clinically unique phenotype. Significant differences in steroid metabolism between clusters are only partly reflected by gestational age and disease severity. In early preterm infants, higher excretion rates of glucocorticoids and their precursors were associated with severe cerebral hemorrhage. High excretion rates of C19-steroids in preterm infants may indicate a biological significance.

Pre-eclampsia (PE) is a placenta-mediated disease and remains a major cause of maternal and neonatal mortality and morbidity. As PE develops, normal pregnancy’s hypercoagulable balance is disrupted, leading to platelet hyperactivation, excessive pathological hypercoagulability, and perturbed fibrinolysis. This narrative review aims to summarize the current knowledge regarding hemostasis in PE compared with healthy gestation and the potential effects of maternal PE on neonatal hemostasis. Finally, it aims to discuss hemostasis assessments for normal pregnancies and PE, emphasizing the role of viscoelastic tests, namely, thromboelastography (TEG) and thromboelastometry (ROTEM), for monitoring PE-associated hemostatic alterations. The use of TEG/ROTEM for assessing the hemostatic profile of PE women has been little considered, even though conventional coagulation tests (CCTs) have not helped to monitor hemostasis in this population. Compared with normal pregnancy, TEG/ROTEM in PE reveals an excessive hypercoagulability analogous with the severity of the disease, characterized by higher-stability fibrin clots. The TEG/ROTEM parameters can reflect PE severity and may be used for monitoring and as predictive markers for the disease.

Human milk is the gold standard for infant nutrition, but when it is not available or insufficient to satisfy the needs of the infant, formula milk is proposed as an effective substitute. A prospective observational cohort study was conducted on late preterm infants fed with breast and two different formula milks. On this basis, they were divided into three groups: group FMPB (fed with formula + postbiotic), group FM (fed with standard formula), and group BM (breastfed). Stool samples for a metabolomic study were collected at T0 (5–7 days after birth), T1 (30 days of life), and T2 (90 days of life), giving rise to 74 samples analyzed via liquid chromatography coupled with high-resolution mass spectrometry. The T0, T1, and T2 LC-MS raw data were processed for Partial Least Square Discriminant Analysis (PLS-DA), followed by a statistical analysis. This preliminary study highlighted a good overlapping between the fecal metabolome of breast and substitute feeding systems, confirming the efficacy of the formula preparations as breast milk substitutes. Moreover, several similarities were also detected between the FMPB and BM metabolome, highlighting that the addition of a postbiotic to standard formula milk could be more effective and considered a better alternative to breast milk.

What role does visual experience play in the development of object recognition? Prior controlled-rearing studies suggest that newborn animals require slow and smooth visual experiences to develop object recognition. Here, we examined whether the development of object recognition also requires experience with the surface features of objects. We raised newborn chicks in automated controlled-rearing chambers that contained a single virtual object, then tested their ability to recognize that object from familiar and novel viewpoints. When chicks were reared with an object that had surface features, the chicks developed view-invariant object recognition. In contrast, when chicks were reared with a line drawing of an object, the chicks failed to develop object recognition. The chicks reared with line drawings performed at chance level, despite acquiring over 100 h of visual experience with the object. These results indicate that the development of object recognition requires experience with the surface features of objects.

Background: Developmental dysplasia of the hip (DDH) is a prevalent orthopaedic disorder in children, and screening methods vary across regions due to local health policies. The purpose of this review is to systematise the different ultrasound screening strategies for detecting DDH in newborns in Europe. Methods: Eligible studies from the PubMed, Embase, and Scopus databases, published between 1 January 2018 and 18 March 2023, were included. The inclusion criteria specified a European origin, a focus on newborn human patients, and information on ultrasound for DDH detection. Results: In total, 45 studies were included, covering 18 countries. Among them, six nations (Austria, Bosnia and Herzegovina, Poland, Slovenia, the Czech Republic, and Germany) perform universal ultrasound screening. The timing of the first ultrasound varies, with Austria and the Czech Republic within the 1st week, Bosnia and Herzegovina on the day of birth, Poland between 1 and 12 weeks, and Germany before the 6th week. The Graf method is the most popular ultrasound technique used. Conclusions: There is no consensus on the optimal DDH detection approach in Europe. Varied screening methods stem from epidemiological, cultural, and economic differences among countries.

The effectiveness of probiotics in reducing the incidence of necrotizing enterocolitis has been supported by a very large number of studies. However, the utilization of probiotics in preterm infants remains a topic of debate. This study aims to assess the rate of probiotic use in European neonatal intensive care units (NICUs), compare administration protocols, and identify barriers and concerns associated with probiotic use. An online questionnaire was distributed via email to European NICUs between October 2020 and June 2021. Different questions related to the frequency of probiotic use were proposed. Data on probiotic administration protocols and reasons for non-utilization were collected. The majority of responses were from France and Switzerland, with response rates of 85% and 89%, respectively. A total of 21% of French NICUs and 100% of Swiss NICUs reported routine probiotic use. There was significant heterogeneity in probiotic administration protocols, including variations in probiotic strains, administration, and treatment duration. The main obstacles to routine probiotic use were the absence of recommendations, lack of consensus on strain selection, insufficient scientific evidence, and concerns regarding potential adverse effects. The rate of routine probiotic administration remains low in European NICUs, with heterogeneity among protocols. Further trials are necessary to elucidate optimal treatment modalities and ensure safety of administration.

Background: Transportation of sick newborns is a major predictor of outcome. Prompt identification of the sickest newborns allows adequate intervention and outcome optimization. An optimal scoring system has not yet been identified. Aim: To identify a rapid, accurate, and easy-to-perform score predictive for neonatal mortality in outborn neonates. Material and methods: All neonates admitted by transfer in a level III regional neonatal unit between 1 January 2015 and 31 December 2021 were included. Infants with congenital critical abnormalities were excluded (N = 15). Gestational age (GA), birth weight (BW), Apgar score, place of birth, time between delivery and admission (AT), early onset sepsis, and sick neonatal score (SNS) were collected from medical records and tested for their association with mortality, including in subgroups (preterm vs. term infants); GA, BW, and AT were used to develop MSNS-AT score, to improve mortality prediction. The main outcome was all-cause mortality prediction. Univariable and multivariable analysis, including Cox regression, were performed, and odds ratio and hazard ratios were calculated were appropriate. Results: 418 infants were included; 217/403 infants were born prematurely (53.8%), and 20 died (4.96%). Compared with the survivors, the non-survivors had lower GA, BW, and SNS scores (p < 0.05); only the SNS scores remained lower in the subgroup analysis. Time to admission was associated with an increased mortality rate in the whole group and preterm infants (p < 0.05). In multiple Cox regression models, a cut-off value of MSNS-AT score ≤ 10 was more precise in predicting mortality as compared with SNS (AUC 0.735 vs. 0.775) in the entire group and in the preterm infants group (AUC 0.885 vs. 0.810). Conclusions: The new MSNS-AT score significantly improved mortality prediction at admission in the whole study group and in preterm infants as compared with the SNS score, suggesting that, besides GA and BW, AT may be decisive for the outcome of outborn preterm infants.

During Integrated Multiparametric Neurophysiological Monitoring (IMNA), a newborn with suspected hypoxia at birth and microhaemorrhagic and ischaemic lesions presented some clonic-tonic episodes with specific EEG patterns characterized by rolandic and temporal spikes and the appearance of a unilateral enhanced Somatosensory Evoked Potential (SEP) (10.45 µv). Since the literature does not seem to describe cases of giant SEP in newborns, in this case report, we will discuss the hypotheses underlying this potential. It could be assumed that the ischaemic and haemorrhagic lesions presented by the newborn may have developed as a result of neurotransmitter balance failure. This may be the origin of the EEG picture, which, consequently, could have triggered a potential with high amplitude.

Objective: To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the lower-middle São Francisco region. Methods: This is an analytical cohort and exploratory. Thirty children, were formed two groups, one of low birth weight children (LBW, n = 15) and another of normal weight (NBW = 15) were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves were measured at birth and the third and sixth months of life. Results: Weight gain during the 6 months of follow-up in newborns with a low birth weight was greater compared to newborns with a normal birth weight. All children who were born with a low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with a low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with a low birth weight. Conclusions: Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with a low birth weight with greater adiposity in this group which may increase the risk of metabolic diseases in later life.

Pregnancy and lactation are critical periods for human well-being and are sensitive windows for pollutant exposure. Bisphenol A (BPA) is well demonstrated as a toxicant and has been replaced in the plastic industry with other bisphenol analogs that share similarities in structure and characteristics, most commonly Bisphenol S (BPS) and Bisphenol F (BPF). Maternal exposure to BPS or BPF can result in their accumulation in the fetal compartment, leading to chronic exposure and potentially limiting normal fetal growth and development. This review summarizes considerable findings of epidemiological or experimental studies reporting associations between BPS or BPF and impaired fetal growth and development. Briefly, the available findings indicate that exposure to the two bisphenol analogs during pregnancy and lactation can result in multiple disturbances in the offspring, including fetal growth restrictions, neurological dysfunctions, and metabolic disorders with the potential to persist throughout childhood. The occurrence of premature births may also be attributed to exposure to the two bisphenols. The possible mechanisms of actions by which the two bisphenols can induce such effects can be attributed to a complex of interactions between the physiological mechanisms, including impaired placental functioning and development, dysregulation of gene expression, altered hormonal balance, and disturbances in immune responses as well as induced inflammations and oxidative stress. In conclusion, the available evidence suggests that BPS and BPF have a toxic potential in a compartment level to BPA. Future research is needed to provide more intensive information; long-term studies and epidemiological research, including a wide scale of populations with different settings, are recommended. Public awareness regarding the safety of BPA-free products should also be enhanced, with particular emphasis on educating individuals responsible for the well-being of children.

Objective: Lactate is a marker of hypoperfusion in critically ill patients. Whether lactate is useful for identifying and stratifying neonates with a higher risk of adverse outcomes remains unknown. This study aimed to investigate the association between lactate and morbidity and mortality in neonates. Methods: A meta-analysis was performed to determine the association between blood lactate levels and outcomes in neonates. Ovid MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched from inception to 1 May 2021. A total of 49 observational studies and 14 data accuracy test studies were included. The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the QUADAS-2 tool for data accuracy test studies. The primary outcome was mortality, while the secondary outcomes included acute kidney injury, necessity for renal replacement therapy, neurological outcomes, respiratory morbidities, hemodynamic instability, and retinopathy of prematurity. Results: Of the 3184 articles screened, 63 studies fulfilled all eligibility criteria, comprising 46,069 neonates. Higher lactate levels are associated with mortality (standard mean difference, −1.09 [95% CI, −1.46 to −0.73]). Using the estimated sensitivity (0.769) and specificity (0.791) and assuming a prevalence of 15% for adverse outcomes (median of prevalence among studies) in a hypothetical cohort of 10,000 neonates, assessing the lactate level alone would miss 346 (3.46%) cases (false negative) and wrongly diagnose 1776 (17.76%) cases (false positive). Conclusions: Higher lactate levels are associated with a greater risk of mortality and morbidities in neonates. However, our results do not support the use of lactate as a screening test to identify adverse outcomes in newborns. Research efforts should focus on analyzing serial lactate measurements, rather than a single measurement.

Oxidative stress (OS) constitutes a pivotal factor within the mechanisms underlying brain damage, for which the immature brain is particularly vulnerable. This vulnerability is caused by the abundance of immature oligodendrocytes in the immature brain, which are highly susceptible to OS-induced harm. Consequently, any injurious process involving OS within the immature brain can lead to long-term myelination impairment. Among the detrimental repercussions of OS, protein carbonylation stands out as a prominently deleterious consequence. Noteworthy elevation of protein carbonylation is observable across diverse models of neonatal brain injury, following both diffuse and focal hypoxic–ischemic insults, as well as intraventricular hemorrhage, in diverse animal species encompassing rodents and larger mammals, and at varying stages of brain development. In the immature brain, protein carbonylation manifests as a byproduct of reactive nitrogen species, bearing profound implications for cell injury, particularly in terms of inflammation amplification. Moreover, protein carbonylation appears as a therapeutic target for mitigating neonatal brain damage. The administration of a potent antioxidant, such as cannabidiol, yields substantial neuroprotective effects. These encompass the reduction in cerebral damage, restoration of neurobehavioral performance, and preservation of physiological myelination. Such effects are linked to the modulation of protein carbonylation. The assessment of protein carbonylation emerges as a reliable method for comprehending the intricate mechanisms underpinning damage and neuroprotection within neonatal brain injury.

Germline manipulation at the zygote stage using the CRISPR/Cas9 system has been extensively employed for creating genetically modified animals and maintaining established lines. However, this approach requires a long and laborious task. Recently, many researchers have attempted to overcome these limitations by generating somatic mutations in the adult stage through tail vein injection or local administration of CRISPR reagents, as a new strategy called “in vivo somatic cell genome editing”. This approach does not require manipulation of early embryos or strain maintenance, and it can test the results of genome editing in a short period. The newborn is an ideal stage to perform in vivo somatic cell genome editing because it is immune-privileged, easily accessible, and only a small amount of CRISPR reagents is required to achieve somatic cell genome editing throughout the entire body, owing to its small size. In this review, we summarize in vivo genome engineering strategies that have been successfully demonstrated in newborns. We also report successful in vivo genome editing through the neonatal introduction of genome editing reagents into various sites in newborns (as exemplified by intravenous injection via the facial vein), which will be helpful for creating models for genetic diseases or treating many genetic diseases.