Search Results (20)

Objectives: Pulmonary hypertension and hemodynamically significant PDA (hsPDA) involve seemingly opposite physiological features—decreased pulmonary blood flow and pulmonary overcirculation, respectively—but the literature demonstrates variable respiratory consequences in association with each of these morbidities. The aim of this study is to evaluate whether the two factors representing pulmonary circulation provide different contributions to respiratory outcomes in preterm infants with and without pulmonary hypoplasia. Methods: The medical records of preterm very low birth weight (VLBW) infants admitted to our unit during the study period from January 2013 to December 2020 were retrospectively reviewed. Preterm VLBW infants were divided into groups according to the presence of presumed pulmonary hypoplasia (PPH). Multivariable logistic regression analysis was performed to assess the association of PPH and pulmonary hypertension or delayed PDA closure with in-hospital outcomes. Results: Postnatal age at final treatment for PDA was significantly later [median 33 vs. 19 days, p = 0.025] in the PPH group. Multivariable analysis indicated that early pulmonary hypertension was significantly associated with neonatal death [aOR (95%CI) 11.575 (2.988–44.833) for no-PPH vs. 9.981 (1.334–74.647) for PPH]. Delayed PDA closure was associated with increased odds of adverse respiratory and composite outcomes [aOR (95%CI) 4.929 (1.613–15.055) and 3.320 (1.048–10.515), respectively] but decreased odds of neonatal death in the no-PPH group. However, Cox proportional hazards models did not demonstrate statistically significant associations for PPH, early pulmonary hypertension, or delayed PDA closure with mortality, likely due to time-varying effects and the absence of death events in the subgroup of infants with both PPH and delayed PDA closure. Conclusions: PPH is associated with a higher prevalence of air leak syndrome and pulmonary hypertension. Delayed PDA closure exerts different effects on respiratory outcomes in preterm VLBW infants with and without PPH. Although early pulmonary hypertension appears to be a key circulatory factor contributing to neonatal death, its effect may vary over time. These findings underscore the importance of accounting for time-dependent effects when interpreting pulmonary circulatory risk factors in clinical practice. Full article

Background: Very-low-birth-weight infants (VLBWIs; birth weight < 1500 g) are at an increased risk of complicated influenza infection, which frequently includes pneumonia, encephalitis or even death. Data on influenza immunization and its outcome in VLBWIs are scarce. This study aimed to provide epidemiological data on influenza immunization for German VLBWIs and hypothesized that immunization would protect VLBWIs from infection-mediated neurodevelopmental impairment and preserves lung function at early school age. Methods: In this observational population-based German Neonatal Network (GNN) study, infants born between 2009 and 2015 were invited to partake in a 6-year follow-up investigation including lung function and developmental testing. Uni- and multivariate analyses were performed to evaluate the clinical characteristics and outcomes of influenza-immunized VLBWIs compared to non-immunized VLBWIs. Results: Influenza immunization was performed in 871 out of the 3358 VLBWIs (26%) with six-year follow-up. Immunized infants were characterized by a low gestational age and higher rates of morbidity, particularly bronchopulmonary dysplasia. Although early immunization showed no safety signals and had protective effects on the long-term risk of bronchitis (OR: 0.2; CI: 0.1–0.6; p = 0.002), most VLBWIs (88.0%) were unimmunized in their first influenza season. Conclusions: Influenza immunization was not associated with improved lung function (forced expiratory volume in one second and forced vital capacity) or a better neurocognitive outcome (intelligence quotient and strengths and difficulties questionnaire) at early school age. In Germany, only one quarter of 6-year-old VLBWIs were immunized against influenza, particularly those born <28 gestational weeks and/or BPD. Specific influenza immunization guidelines that define evidence-based recommendations are needed for this vulnerable group. Full article

Introduction: Children born small or sick are at risk of death and poor development, but many lack access to preventative follow-up services. We assessed the impact of Pediatric Development Clinics (PDC), which provide structured follow-up after discharge from hospital neonatal care units, on children’s survival, nutrition and development in rural Rwanda. Methods: This quasi-experimental study compared a historic control group to children receiving PDC in Kayonza and Kirehe districts. Study populations in both districts included children born preterm or with birthweight < 2000 g and discharged alive. Kirehe additionally included children with hypoxic ischemic encephalopathy (HIE). Home-based cross-sectional surveys were conducted in Kayonza among children with expected chronological age 11–36 months in 2014 (controls) and 2018 (PDC group) and in Kirehe among children with expected chronological age 17–39 months in 2018 (controls) and 2019 (PDC group). Outcomes were measured using anthropometrics and the Ages and Stages Questionnaires. We used weighted logistic regression to control for confounding and differential non-participation. Results: PDC children (n = 464/812, 57.1%) were significantly more likely to participate in surveys (83.0% vs. 65.5%), have very low birthweight (27.6% vs. 19.0%), and be younger at the survey (26.2 vs. 31.1 months). 6.9% (n = 56) died before the survey. PDC was associated with reduced odds of death (aOR = 0.49, 95% CI: 0.26–0.92) and reduced odds of developmental delay (aOR = 0.48, 95% CI: 0.30–0.77). In Kayonza, PDC was associated with reduced stunting (aOR = 0.52, 95% CI: 0.28–0.98). PDC was not associated with reduced underweight or wasting. Conclusions: PDC was associated with improved survival and development among children born preterm, with low birthweight, or with HIE. Increased access to PDC, scale-up across Rwanda, and implementation of similar services and early intervention in other low-resource settings could support children born small or sick. Full article

Background/Objectives: Pneumothorax can be a major complication of neonatal lung diseases. We aim to delineate trends and describe the main outcomes related to pneumothorax in very preterm infants (VPI). Methods: Preterm infants < 32 weeks of gestation admitted in two-level III neonatal intensive care units (1995–2019) were included. Risk factors and outcomes were assessed by logistic regression and adjusted for gestational age (GA). Results: In total, 4271 VPI with a mean GA of 28.7 ± 2.3 weeks were evaluated. Pneumothorax was diagnosed in 174 patients (4.1%, 95% Confidence Interval (CI) 3.5–4.7) with its incidence inversely proportional to GA: 9.9% in 23–25 w and 2.1% in 30–31 w (p < 0.001), but stable over the years 1995–1999 (5.2%) and 2015–2019 (4.2%) (p = 0.309). Patients with pneumothorax exhibited higher rates of severe intraventricular hemorrhage (IVH) (Odds Ratio (OR) = 2.0 (95%CI 1.3–3.1), p = 0.003), bronchopulmonary dysplasia (OR = 2.7 (95%CI 1.7–4.4), p < 0.001), and death (OR = 8.5 (95%CI 6.2–11.6), p < 0.001). Independent risk factors for pneumothorax were GA, prolonged premature rupture of membranes, and intubation in the delivery room. The composite outcome of death or severe IVH was higher in patients with pneumothorax with an adjusted OR = 6.7 (95%CI 4.7–9.6), p < 0.001. Although VPI mortality has significantly decreased over the years (20.3% 1995–1999 and 11.7% 2015–2019, p < 0.001), we found no significant difference in pneumothorax-related deaths. Conclusion: Pneumothorax remains a serious threat to VPI, leading to a higher incidence of morbidity, and mortality attributable to this complication has not decreased. Preventive strategies and early recognition are essential for improving disability-free survival in VPI. Full article

Pregnancy loss (PL) in dairy cattle results in animal health and welfare disruption and has a great economic impact on farms, with decreases in fertility and increased culling. It can occur at any stage of embryonic or fetal development. Abortion occurring from the second half of pregnancy has a more negative impact on dairy farms. There are several infectious and non-infectious factors that can lead to PL and vary according embryonic or fetal stages. As this is a multifactorial or multi-etiological occurrence, it is important to identify the risk factors and the best diagnostic tools to approach these reproductive losses that can occur sporadically or by outbreaks. Reaching a final diagnosis can be challenging, especially when it occurs at a very early stage of pregnancy, where losses may not be detected and neonatal deaths may be related to alterations in the fetus in utero. Also, laboratorial results from animal samples should be interpreted according to the full clinical approach. This review aimed to highlight all these essential aspects, identifying the main infectious and non-infectious causes leading to PL, as well as the best veterinary practices for diagnosing it, mainly through transrectal palpation, ultrasound, and laboratory methods, in bovine dairy farms. Full article

The objective of this study was to assess the relationship of ACS with neonatal outcomes among very preterm infants born to mothers with clinical chorioamnionitis in China. This was a multicenter retrospective cohort study. Study participants included infants born at <32 weeks’ gestation with clinical chorioamnionitis and registered in the Chinese Neonatal Network from 1 January 2019 to 31 December 2020. Infants were divided into two groups: any amount of ACS or no administration of ACS. Multivariable generalized linear models using generalized estimating equations were used to assess the association between ACS and neonatal outcomes among the study population. We identified 2193 infants eligible for this study; 1966 (89.6%) infants had received ACS therapy, and 227 (10.4%) had not received any ACS therapy. Among very preterm infants born to mothers with clinical chorioamnionitis, any ACS usage was significantly associated with decreased risks of early death (aRR 0.56, 95% CI 0.32, 0.99) and severe ROP (aRR 0.51, 95% CI 0.28, 0.93) after adjustment for maternal hypertension, gestational age at birth, Caesarean section, being inborn, and administration of systemic antibiotics to the mother within 24 h before birth. In addition, out of the 2193 infants, the placentas of 1931 infants underwent pathological examination with recorded results. Subsequently, 1490 of these cases (77.2%) were diagnosed with histological chorioamnionitis. In 1490 cases of histologic chorioamnionitis, any ACS usage was significantly related to decreased risks of overall mortality (aRR 0.52, 95% CI 0.31, 0.87), severe ROP (aRR 0.47, 95% CI 0.25, 0.97), and respiratory distress syndrome (aRR 0.52, 95% CI 0.31, 0.87). We concluded that any ACS was associated with reduced risks for neonatal early death and severe ROP among very preterm infants born to mothers with clinical chorioamnionitis. Full article

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. Full article

The second most prevalent healthcare-associated infection in neonatal intensive care units (NICUs) is ventilator-associated pneumonia (VAP). This review aims to update the knowledge regarding the incidence of neonatal VAP and to summarize possible strategies for prevention. The VAP incidence ranges from 1.4 to 7 episodes per 1000 ventilator days in developed countries and from 16.1 to 89 episodes per 1000 ventilator days in developing countries. This nosocomial infection is linked to higher rates of illness, death, and longer hospital stays, which imposes a substantial financial burden on both the healthcare system and families. Due to the complex nature of the pathophysiology of VAP, various approaches for its prevention in the neonatal intensive care unit have been suggested. There are two main categories of preventative measures: those that attempt to reduce infections in general (such as decontamination and hand hygiene) and those that target VAP in particular (such as VAP care bundles, head of bed elevation, and early extubation). Some of the interventions, including practicing good hand hygiene and feeding regimens, are easy to implement and have a significant impact. One of the measures that seems very promising and encompasses a lot of the preventive measures for VAP are the bundles. Some preventive measures still need to be studied. Full article

Doppler findings of persistent reverse end-diastolic flow (PREDF) in a fetal middle cerebral artery (MCA) are a very rare sonographic finding and are a marker of poor fetal condition. This finding often leads to intrauterine fetal death or early neonatal death. Reverse end-diastolic flow in the middle cerebral artery is an advanced hemodynamic event. Fetal cerebral circulation normally has a high impedance; in the event of fetal hypoxemia, impedance decreases, resulting in the central redistribution of blood flow to vital organs, which maintains the oxygen delivery to the brain. Reverse flow in the middle cerebral arteries describes the loss of this autoregulatory process. PREDF is a sequence that occurs due to increased extracranial or intracranial pressure. Previous case reports mentioned intracranial hemorrhage, fetal growth restriction, fetal anemia, and fetal hepatic abnormalities as problems leading to PREDF. This condition presumably arises due to cerebral edema associated with severe hypoxemia. We reported Doppler findings of PREDF MCA in a 33-year-old female patient at 30 weeks gestation who was referred to the hospital with severe preeclampsia accompanied by fetal growth restriction and oligohydramnios. A cesarean section was performed due to severe preeclampsia and a low bishop score. Hypotheses on various etiologies and their association with intrauterine/neonatal death as well as the best management still require further investigation. Full article

Perinatal asphyxia is a complex disease involving massive death of brain cells in full-term newborns. The most impressive consequence of perinatal asphyxia is a neurodegenerative brain injury called hypoxic–ischemic encephalopathy. Management of newborns after perinatal asphyxia is very difficult due to the lack of measurable biomarkers that would be able to assess the severity of the brain injury in the future, help in the selection of therapy, assess the results of treatment and determine the prognosis for the future. Thus, these limitations make long-term neurodevelopmental outcomes unpredictable during life. Quantifying biomarkers that can detect subclinical changes at a stage where routine brain monitoring or imaging is still mute would be a major advance in the care of neonates with brain neurodegeneration after asphyxia. Understanding the effect of perinatal asphyxia on changes in blood neurodegenerative biomarkers over time, which would be commonly used to assess the severity of postpartum encephalopathy, would be an important step in developing precision in predicting the consequences of brain injuries. We urgently need more accurate early predictive markers to guide clinicians when to use neuroprotective therapy. The needed neurodegenerative biomarkers may represent neuronal pathological changes that can be recognized by new technologies such as genomic and proteomic. Nevertheless, the simultaneous blood tau protein and various amyloid changes with the addition of an autophagy marker beclin 1 after perinatal asphyxia have not been studied. We decided to evaluate serum biomarkers of neuronal injury characteristic for Alzheimer’s disease such as amyloid peptides (1-38, 1-40 and 1-42), tau protein and beclin 1, which can predict the progression of brain neurodegeneration in future. In this paper, we report for the first time the significant changes in the above molecules in the blood after asphyxia compared to healthy controls during the 1–7, 8–14 and 15+ days ELISA test. Full article

Myocardial injury causes death to cardiomyocytes and leads to heart failure. The adult mammalian heart has very limited regenerative capacity. However, the heart from early postnatal mammals and from adult lower vertebrates can fully regenerate after apical resection or myocardial infarction. Thus, it is of particular interest to decipher the mechanism underlying cardiac regeneration that preserves heart structure and function. RNA-binding proteins, as key regulators of post-transcriptional gene expression to coordinate cell differentiation and maintain tissue homeostasis, display dynamic expression in fetal and adult hearts. Accumulating evidence has demonstrated their importance for the survival and proliferation of cardiomyocytes following neonatal and postnatal cardiac injury. Functional studies suggest that RNA-binding proteins relay damage-stimulated cell extrinsic or intrinsic signals to regulate heart regenerative capacity by reprogramming multiple molecular and cellular processes, such as global protein synthesis, metabolic changes, hypertrophic growth, and cellular plasticity. Since manipulating the activity of RNA-binding proteins can improve the formation of new cardiomyocytes and extend the window of the cardiac regenerative capacity in mammals, they are potential targets of therapeutic interventions for cardiovascular disease. This review discusses our evolving understanding of RNA-binding proteins in regulating cardiac repair and regeneration, with the aim to identify important open questions that merit further investigations. Full article

Background: COVID-19 is an emerging global pandemic with potential adverse effects during pregnancy. This study aimed to determine the adverse maternal and foetal outcomes due to COVID-19 infection. We also compared maternal and neonatal outcomes with regard to the timing of diagnosis (first and second trimester vs. third and fourth trimester); early COVID-19 (stage I and II) vs. severe-stage COVID-19 (III, IV, and V); and lastly, women who were partially vaccinated vs. unvaccinated. Methods: This was a retrospective study conducted in HCTM from January 2021 to January 2022. All pregnant women admitted for COVID-19 infections were recruited. The patients’ records were traced. Adverse maternal and neonatal outcomes were documented and analysed. Results: There were 172 pregnant women recruited into this study. We excluded twenty-four patients with incomplete data and nine women who delivered elsewhere. The final 139 patients were available for data analysis. The majority of women were in their third trimester of pregnancy (87.8%); however, only 5.0% and 7.2% were in the first and second trimesters, respectively. The study population had a median BMI of 29.1 kg/m² and almost half of them had never received a COVID-19 vaccination. A sub-analysis of data concerning adverse maternal and foetal outcomes comparing early vs. severe stages of COVID-19 infection showed that severe-stage disease increased the risk of preterm birth (54.5% vs. 15.4%, p < 0.001) and preterm birth before 34 weeks (31.9% vs. 2.6%, p < 0.001) significantly. The severe-stage disease also increased NICU admission (40.9% vs. 15.4%, p = 0.017) with lower birth weight (2995 g vs. 2770 g, p = 0.017). The unvaccinated mothers had an increased risk of preterm birth before 34 weeks and this was statistically significant (11.6% vs. 2.9%, p = 0.048). Conclusions: Adverse pregnancy outcomes such as ICU admission or patient death could occur; however, the clinical course of COVID-19 in most women was not severe and the infection did not significantly influence the pregnancy. The risk of preterm birth before 34 weeks was higher in a more severe-stage disease and unvaccinated mother. The findings from this study can guide and enhance antenatal counselling of women with COVID-19 infection, although they should be interpreted with caution in view of the very small number of included cases of patients in the first and second trimesters. Full article

Background: Midwives working in settings with limited clinical resources experience high rates of very early neonatal deaths. Midwives manage the impact of this grief and trauma almost daily, which may affect patient care and their own well-being. Research Aims: To explore how midwives are impacted by and cope with high rates of very early neonatal deaths. To document midwives’ insights and local solutions that may reduce very early neonatal deaths in limited resource settings. To document the stories of midwives in order to create awareness and garner support for midwives and their critical work in low resource settings. Methods: Narrative inquiry utilizing semi structured interviews. Twenty-one midwives with at least six months experience who had experienced or witnessed very early neonatal death were interviewed. Data were audio recorded and transcribed, and reflexive thematic analysis of transcripts was conducted. Results and Discussion: Three themes were identified: (1) deep sadness resulting from very early neonatal deaths leading to internal struggles; (2) use of spirituality, including prayer and occasional beliefs that unexplainable deaths were ‘God’s plan’; and (3) development of resilience by seeking solutions, educating themselves, taking accountability and guiding mothers. Participating midwives noted that inadequate staff and high caseloads with limited basic supplies hindered their clinical practice. Participants articulated that they concentrated on active solutions to save babies during labour, such as vigilant foetal rate heart monitoring and partogram. Further, reduction and prevention of very early neonatal death is a complex problem requiring multidisciplinary teams and woman-centred care approaches to address issues contributing to the health of mothers and their new-borns. Conclusions: Midwives’ narratives highlighted ways of coping with grief and deep sadness, through prayer, and further education of both mothers and fellow colleagues to achieve better antenatal and intrapartum care and outcomes. This study gave midwives an opportunity for their voices to be heard and to generate solutions or insights that can be shared with colleagues in similar low-resource settings. Full article

Background and Objectives: In this study, we aimed to describe the clinical and ultrasound (US) features and the outcome in a group of patients suspected of or diagnosed with early onset intrauterine growth restriction (IUGR) requiring iatrogenic delivery before 32 weeks, having no structural or genetic fetal anomalies, managed in our unit. A secondary aim was to report the incidence of the condition in the population cared for in our hospital, data on immediate postnatal follow-up in these cases and to highlight the differences required in prenatal and postnatal care. Materials and Methods: We used as single criteria for defining the suspicion of early IUGR the sonographic estimation of fetal weight < p10 using the Hadlock 4 technique at any scan performed before 32 weeks’ gestation (WG). We used a cohort of patients having a normal evolution in pregnancy and uneventful vaginal births as controls. Data on pregnancy ultrasound, characteristics and neonatal outcomes were collected and analyzed. We hypothesized that the gestational age (GA) at delivery is related to the severity of the condition. Therefore, we performed a subanalysis in two subgroups, which were divided based on the GA at iatrogenic delivery (between 27+0 WG and 29+6 WG and 30+0–32+0 WG, respectively). Results: The prospective cohort study included 36 pregnancies. We had three cases of intrauterine fetal death (8.3%). The incidence was 1.98% in our population. We confirmed that severe cases (very early diagnosed and delivered) were associated with a higher number of prenatal visits and higher uterine arteries (UtA) pulsatility index (PI) centile in the third trimester—TT (compared with the early diagnosed and delivered). In the very early suspected IUGR subgroup, the newborns required significantly more NICU days and total hospitalization days. Conclusions: Patients with isolated very early and early IUGR—defined as ultrasound (US) estimation of fetal weight < p10 using the Hadlock 4 technique requiring iatrogenic delivery before 32 weeks’ gestation—require closer care prenatally and postnatally. These patients represent an economical burden for the health system, needing significantly longer hospitalization intervals, GA at birth and UtA PI centiles being related to it. Full article

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00–0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00–0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02–0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics. Full article