Neonatology最新文献

Introduction: Intrauterine herpes simplex virus (HSV) infection is uncommon and challenging to diagnose, requiring detection of HSV in skin lesions within 48 h post-birth.

Case presentation: A preterm female infant presented with the typical triad of blisters, microcephaly, and chorioretinitis, but the initial diagnostic approach was elusive due to negative results for TORCH pathogens from vesicles/serum. Referred at 7 months for developmental delay and epilepsy, her brain imaging showed calcification and cortical dysplasia. Polymerase chain reaction (PCR) of her preserved dried umbilical cord detected HSV-2 DNA, diagnosing intrauterine HSV infection. HSV-2 was later found in relapsed blisters at 8 months but not in cerebrospinal fluid or brain tissue. A literature review identified 104 congenital/intrauterine HSV cases; 28.8% presented the typical triad, and 50% were diagnosed using specimens collected 48 h post-birth.

Conclusion: This case marks the first retrospective diagnosis of intrauterine HSV infection via PCR on preserved umbilical cord, underscoring its diagnostic value.

Introduction: Optimal oxygen saturation targets remain unknown for extremely preterm infants.

Methods: Cohort analysis of eligible preterm infants born <29 weeks' gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88-93%) or high (90-95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices.

Results: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72).

Conclusion: For neonates <29 weeks' gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target.

Introduction: Probiotics have shown potential in reducing the occurrence of atopic eczema in high-risk infants. We aimed here to assess whether the preventive effect of maternal probiotic administration stems from compositional changes in early gut microbiota.

Methods: This study included 46 mother-infant pairs from an original randomized controlled trial assessing the impact of maternal probiotic intervention with either the combinations of Lacticaseibacillus rhamnosus LPR and Bifidobacterium longum BL999, or Lacticaseibacillus paracasei ST11 and Bifidobacterium longum BL999, or placebo beginning 2 months before expected delivery and ending 2 months after birth. All children were vaginally delivered, full term and breastfed. During the 2-year follow-up period, the children were clinically evaluated by physicians for atopic eczema, and their gut microbiota was profiled at 1 and 6 months of age by 16S rRNA gene sequencing using an Illumina sequencing platform.

Results: Altogether, 19 of 46 children developed atopic eczema by the age of 2 years. At 1 and 6 months of age, gut microbial diversity was similar between children who developed atopic eczema and their healthy controls, but at the age of 6 months, children who developed atopic eczema manifested with significantly higher relative abundance of Clostridia. Probiotic intervention did not significantly influence microbial diversity, and the effects on microbial composition were not consistent with the changes associated with the development of atopic eczema.

Conclusion: The reduction of the risk of atopic eczema achieved by perinatal maternal probiotic intervention does not seem to require substantial gut microbiota modulation.

Introduction: Pulmonary hypertension often complicates bronchopulmonary dysplasia (BPD) and infants with BPD plus pulmonary hypertension experience higher mortality rates. Current methods to evaluate pulmonary hypertension fail to evaluate the primary cause of this disease. We hypothesize that preterm infants with BPD experience altered pulmonary vascular growth and that magnetic resonance imaging (MRI) can be used to assess vascularity in BPD.

Methods: In this observational cohort study, preterm infants with BPD (n = 33) and controls (n = 6) received a postnatal chest MRI that included a 2-dimensional time-of-flight acquisition. Semi-automatic segmentation was performed to measure vascularity parameters including vascular volume and density (vascular density = vascular volume/lung volume).

Results: Vascular volume on MRI increases with post-menstrual age (877.2 mm3/week); however, the vascular density does not significantly change. Vascular volume is higher in infants with more severe BPD (p < 0.002), but vascular density did not significantly change when comparing mild, moderate, and severe BPD. Vascular density in infants with severe BPD requiring tracheostomy trended lower when compared to infants not requiring tracheostomy (0.18 mm3/mm3 vs. 0.27 mm3/mm3, p = 0.06). Vascular density increases with increasing days of inhaled nitric oxide (iNO) therapy in infants with severe BPD (0.02 mm3/mm3/week of iNO, rho = +0.56, p = 0.03).

Conclusion: Neonatal MRI can be used to assess pulmonary vascularity in preterm infants with BPD. Infants with BPD experience altered vascular growth and while higher vascular volume is associated with more severe BPD, lower vascular density trends toward worse clinical outcomes. Vascular density increases with iNO therapy in severe BPD.

Introduction: Preterm newborns struggle with maintaining an adequate respiratory pattern; early caffeine administration is suggested to stimulate respiration and reduce bronchopulmonary dysplasia, however, its consequences on the immature cerebellum remains unknown. This study aimed to assess the impact of early caffeine administration, at standard and high doses, accompanied by supplemental oxygen on cerebellar development in an experimental model.

Methods: Five groups of Wistar pups were formed (n = 8 offspring/group): (a) negative control: no intervention; (b) placebo: pups remaining from birth until the 7th day of life (DOL) exposed to fractional inspired oxygen (FiO2) 45%, resembling preterm infant condition and as a placebo, 0.2 mL oral 5% dextrose, from the first DOL until the 14th DOL; (c) caffeine group: oral caffeine, 1st DOL 20 mg/kg, and from 2nd to 14th DOL, 5 mg/kg (standard dose); (d) caffeine at the standard dose, plus O2: during the first 7 DOLs (FiO2: 45%); (e) caffeine: 40 mg/kg in the first DOL, 10 mg/kg the next 14 DOLs, plus O2 in the first 7 DOLs (FiO2: 45%). Subjects were sacrificed on their 15th DOL; measurements were taken from the cerebellum, specifically the external granular layer (EGL) and molecular layer (ML), with quantification of cell migration.

Results: Caffeine administration in pups resulted in a delay in cerebellum development based on persistent transitional EGL cells; this finding was exacerbated in groups exposed to caffeine plus O2, as evident from the thicker EGL. The negative control group showed near-complete cell migration with a thicker ML and a significantly smaller EGL.

Conclusions: Early caffeine administration in newborn rats disrupts cerebellar cortex cell processes and connectivity pathways, with exacerbated effects in groups receiving caffeine plus O2.

Introduction: The European guideline for treatment of respiratory distress syndrome recommends less invasive surfactant administration (LISA) as the preferred method of surfactant administration in spontaneously breathing preterm infants. However, there is limited evidence on practical aspects such as sedation and catheter types, leading to considerable variability between centers.

Methods: An anonymous online survey (www.soscisurvey.de) was sent to 164 tertiary neonatal intensive care units (NICUs) in Germany including 43 questions on practical aspects of LISA.

Results: Of 122 (74%) participating NICUs, 117 (96%) reported experience with LISA with 82% of those reporting LISA as their preferred method of surfactant administration. Indications for surfactant administration differed widely between NICUs. Most (89%) used FiO2-thresholds only or in combination with other criteria, such as Silverman score/signs of dyspnea (41%) or lung ultrasound findings (3%). Prophylactic surfactant was administered by 42%. Differences in use of LISA in extremely immature infants were reported (e.g., 36% did not perform LISA in infants below 24-26 weeks). Preferred drugs for sedation were (Es-)Ketamine, followed by Propofol and Midazolam. Minimum time interval between subsequent LISA procedures was 4 (2-6) h. Catheters specifically designed for LISA were used by most NICUs (69%).

Conclusion: This survey shows that LISA is common practice in German NICUs, but with considerable variability in practical aspects. These data may serve as a guidance for NICUs that have not yet implemented LISA and might be helpful design clinical trials with the aim to standardize and/or optimize LISA.

Introduction: Providing adequate nutrition in the management of preterm infants has been challenging. The objective of this secondary analysis of data from the randomized trial comparing "less invasive surfactant therapy (LISA) with InSurE method of surfactant administration" is to demonstrate the feasibility of early total enteral feeding (ETEF) in hemodynamically stable preterm neonates on respiratory support and to examine the factors associated with failure of ETEF.

Methods: Secondary analysis of a randomized controlled trial comparing "LISA versus InSurE among preterm infants between 26 and 34 weeks of gestation" enrolled 150 infants with 117 being hemodynamically stable. ETEF without any parenteral supplementation was started on day 1 of life using the mother's own milk (MoM) or donor human milk (<32 weeks of GA) and MoM or preterm formula (33-34 weeks of GA). The data were analyzed to assess the proportion of babies developing feed intolerance and/or necrotizing enterocolitis (NEC) and factors associated with failure of ETEF. All Infants were assessed for the day of attainment of full enteral feeding defined as receiving and tolerating 150 mL/kg of enteral feeds per day.

Results: Out of these 117 babies, 102 tolerated ETEF, and 15 had one or more episodes of FI requiring total parenteral nutrition, but none developed NEC till discharge or death. On the assessment of possible factors associated with ETEF failure, there were no differences in baseline characteristics but statistically significantly increased incidence of culture-positive sepsis as well as the requirement of antibiotic therapy for possible sepsis (early as well as late-onset sepsis) in babies with failure of ETEF. The babies who tolerated ETEF achieved full enteral feeding (150 mL/kg/day) significantly earlier (5.48 ± 1.1 days) compared to those with ETEF failure (7 ± 3.4 days) (p 0.001). The time to regain birth weight was earlier in the ETEF group without significant differences in growth parameters. There was also a reduction in the duration of hospital stay in babies who tolerated ETEF, but both these results were not statistically significant.

Conclusion: ETEF is feasible in preterm neonates with respiratory distress syndrome who are on respiratory support. It resulted in earlier attainment of full enteral feeds and decreased the incidence of sepsis with reduced antibiotic usage.

Introduction: Birth-related obstruction of umbilical blood flow may induce hypoxic insults that affect postnatal organ adaptation. Using newborn cesarean-delivered pigs, we hypothesized that cord obstruction during delivery negatively affects physiological transition and gut maturation. Further, we investigated if delayed cord clamping (DCC) improves gut outcomes, including sensitivity to formula-induced necrotizing enterocolitis (NEC)-like lesions.

Methods: In experiment 1, preterm (n = 24) and near-term (n = 29) piglets were subjected to umbilical cord obstruction (UCO, 5-7 min in utero), with corresponding pigs delivered without obstruction (CON, n = 17-22). Experiment 2 assessed preterm pigs subjected to delayed cord clamping (n = 30, 60 s) or immediate cord transection with umbilical cord milking (UCM, n = 34). Postnatal vital parameters were recorded, together with a series of gut parameters after 3 days of formula feeding.

Results: UCO induced respiratory-metabolic acidosis in near-term pigs at birth (pH 7.16 vs. 7.32, pCO2 12.5 vs. 9.2 kPa, lactate 5.2 vs. 2.5 mmol/L, p < 0.05). In preterm pigs, UCO increased failure of resuscitation and mortality shortly after birth (88 vs. 47%, p < 0.05). UCO did not affect gut permeability, transit time, macromolecule absorption, six digestive enzymes, or sensitivity to NEC-like lesions. In experiment 2, DCC improved neonatal hemodynamics (pH 7.28 vs. 7.20, pCO2 8.9 vs. 9.9 at 2 h, p < 0.05), with no effects on gut parameters.

Conclusion: UCO and DCC affect neonatal transition and hemodynamics, but not neonatal gut adaptation or sensitivity to NEC-like lesions. Our findings suggest that the immature newborn gut is highly resilient to transient birth-related changes in cord blood flow.