Archives of Disease in Childhood - Fetal and Neonatal Edition最新文献

Objective: To characterise white matter microstructural differences within very preterm (VPT; <33 weeks' gestational age) infants that develop motor impairment in the first 2 years of life.

Design: Cohort study, VPT infants (Cincinnati Infant Neurodevelopment Early Prediction Study) recruited from five level III/IV neonatal intensive care units in the greater Cincinnati area between September 2016 and November 2019.

Setting: Multicentre study; participants received MRI at term-equivalent age at Cincinnati Children's Hospital Medical Center and were followed-up at 2 years corrected age to assess their motor performance.

Patients: Infants born before 33 weeks were eligible.

Main outcomes and measures: Composite motor scores at 2 years corrected age (CA) on the Bayley Scales of Infant and Toddler Development, III. Fractional anisotropy (FA) along the white matter tracts was used to measure white matter microstructure. Motor impairment was defined as Bayley-III motor score <85.

Results: 247 controls and 84 impaired infants were included in the study. Compared with the controls, infants with motor impairment were characterised by location-dependent credible group differences and significantly lower FA in both sensorimotor and non-sensorimotor tracts. A location-specific significant positive association between FA and Bayley scores in the impaired group was observed in multiple sensorimotor tracts and non-sensorimotor tracts. No significant associations were found between FA and Bayley scores in the controls.

Conclusion: VPT infants developing motor impairments show altered inter and intrahemispheric connectivity, with early indications of impaired visual-motor, sensorimotor and thalamo-cortical connectivity, extending beyond sensorimotor tracts.

Objective: To examine neonatal physicians' perceptions of optimistic versus pessimistic prognostic framing when delivering serious news to parents.

Design: Multicentre, double-blind, randomised crossover study.

Setting: Conducted online between February and April 2022 at the University Medical Centre Mainz, Germany.

Participants: Neonatal physicians from tertiary perinatal centres in Germany, Austria, Switzerland and Italy.

Intervention: Participants viewed two scripted videos of a physician-parent conversation about a very preterm infant with severe intraventricular haemorrhage. Both conveyed identical numerical prognostic estimates but differed in framing: emphasising survival without disability (optimistic) or risk of death and impairment (pessimistic).

Main outcome measures: Primary outcome was framing preference. Secondary outcomes included Likert scale ratings of parental preparedness, physician professionalism and compassion, prognostic severity and optimism regarding survival and non-impairment, as well as free-text comments on challenges in prognostic communication.

Results: Of 115 participants, 99 (86%) preferred the optimistic video (period-corrected preference odds (95% CI): 8.6 (7.4 to 9.7)). Optimistic framing was associated with higher ratings of parental preparedness and more favourable evaluations of the consulting physician, including professionalism and compassion, but had no effect on perceived prognostic severity, or optimism about survival or non-impairment. Communication was frequently described as an interpersonal challenge, involving the difficulty of maintaining trust, empathy and hope while communicating under prognostic uncertainty.

Conclusions: Neonatal physicians strongly preferred optimistic framing. Framing effects were primarily affective rather than cognitive and highlight implicit and complex framing biases in neonatal communication.

Trial registration number: German Clinical Trials Register (DRKS), www.drks.de/DRKS00024466.

Background: Adequate lung aeration at birth is essential for a successful transition to extrauterine life. Premature infants are especially vulnerable to injury caused by mechanical ventilation, particularly when exposed to excessive tidal volumes during initial respiratory support.

Objective: To evaluate whether high-frequency oscillatory ventilation (HFOV) initiated at birth facilitates lung aeration and reduces lung inflammation and injury, compared with conventional mechanical ventilation (CMV) in preterm lambs.

Design: Preterm lambs (126±1 days' gestation, term ~148 days) were instrumented to assess blood flow, pressure, oxygenation and blood gases. Lambs were allocated to HFOV (n=6), CMV (n=7) or unventilated control (UVC, n=8) groups. In ventilated groups, respiratory support was initiated during physiological-based cord clamping (PBCC). Lung aeration was assessed by lung ultrasound (LUS) in HFOV lambs. Postmortem lung tissues underwent histological and molecular analyses of inflammation and injury.

Results: HFOV achieved effective respiratory stabilisation using significantly lower tidal volumes compared with CMV (1.7±0.4 vs 6.2±1.5 mL/kg, p<0.0001). LUS confirmed rapid lung aeration following HFOV. Histological analyses revealed significantly fewer CD45-positive and CD163-positive inflammatory cells in HFOV lungs compared with CMV (p<0.001 and p<0.05, respectively). Gene expression profiling demonstrated lower expression of key inflammatory and injury markers in HFOV versus CMV lambs, with some levels approaching those observed in UVC (p<0.05).

Conclusions: HFOV initiated during PBCC supports efficient lung aeration while minimising lung inflammation and injury in preterm lambs. These findings suggest that HFOV may reduce lung inflammation during initial respiratory stabilisation in preterm neonates.

Objective: To study the effect of early-onset neonatal infection on long-term cognitive impairment including intellectual disability and special educational needs.

Methods: A nationwide register-based cohort study was conducted including near-term to term children born between 1997 and 2013 with follow-up until 2021. Early-onset infection was defined as an invasive bacterial infection within the first week after birth defined by either physician-assigned diagnoses or bacterial pathogens cultured from blood or cerebrospinal fluid. Outcomes included diagnoses of intellectual disability and special educational needs. Associations were estimated by adjusted HRs (aHR) or unadjusted incidence rate ratios (IRR), when exposures and outcomes were rare. Additional analyses were conducted, including sibling-matched analyses and subgroup analyses considering only children with culture-positive infection.

Results: Among 993 363 children, 8267 (0.8%) had sepsis and 152 (<0.1%) had meningitis. Of these, 260 had culture-positive sepsis and 31 had culture-positive meningitis. Early-onset sepsis was associated with an increased risk of intellectual disability (aHR: 2.24, 95% CI 1.93 to 2.59) and special educational needs (aHR: 1.49, 95% CI 1.40 to 1.59). Early-onset meningitis was associated with higher risks of both intellectual disability (IRR: 7.75, 95% CI 3.34 to 15.27) and special educational needs (aHR: 2.95, 95% CI 2.06 to 4.22). The associations remained consistent across multiple additional analyses, including sibling-matched analyses and subgroup analyses limited to culture-positive infections.

Conclusions: Early-onset neonatal infection in near-term to term children was associated with an increased risk of long-term cognitive impairment including both intellectual disability and special educational needs.

Objective: To evaluate diffuse white matter abnormality (DWMA) volume at term-equivalent age as an independent predictor of neurodevelopmental outcomes in preterm infants.

Study design: In this multicentre prospective cohort study, 392 preterm infants (≤32 weeks' gestation) underwent term-equivalent MRI with automated DWMA quantification. The primary outcome was cognitive function at 3 years corrected age using the Differential Ability Scales-II General Conceptual Ability (GCA) score. Secondary outcomes included motor function (Bayley-III) and cerebral palsy (CP) at 2 years. Multivariable regression analysed DWMA's prognostic value.

Results: Follow-up was available for 89% (GCA) and 87% (Bayley-III/CP) of participants (mean gestational age 29 (SD: 2.5 weeks). Mean GCA was 94 (20.2); Bayley motor composite was 93 (14.5). CP was diagnosed in 12% of children (28 Gross Motor Function Classification System level I, six level II and III and five level IV and V). Higher DWMA volume independently predicted lower cognitive (β=-1.9; 95% CI -3.7 to -0.1), though only marginally over existing predictors (p=0.04), and motor scores (β=-2.0; 95% CI -3.3 to -0.7; p=0.003) and increased CP risk (adjusted OR=1.7; 95% CI 1.2 to 2.4; p=0.003) after controlling for clinical and socioeconomic factors. Socioeconomic disadvantages have amplified DWMA's adverse effects.

Conclusions: This first external validation study demonstrates that objective DWMA quantification independently predicts multiple developmental outcomes through age 3 in preterm infants. The findings validate DWMA's pathological significance and support its utility as an early biomarker for risk stratification and targeted intervention.

Objective: To quantify regional and unit variations in antibiotic use during the first week of life, incidence of early-onset sepsis (EOS) and mortality in late-preterm and term newborns in Sweden.

Design: A nationwide cohort study.

Setting: The Swedish Neonatal Quality Register, a register of all newborns admitted for neonatal care in Sweden.

Patients: All late-preterm and term newborns (≥34 weeks' gestation) admitted to a neonatal unit from 1 January 2012 to 31 December 2020.

Main outcome measures: The proportion of antibiotic use, incidence of EOS and mortality in late-preterm and term newborns.

Results: Out of 1 025 515 newborns, 19 286 neonates (1.9%) received antibiotics with a 2-fold to 5-fold variation across regions (1.3%-3.0%) and units (0.9%-4.3%). Duration of antibiotic therapy (median) varied across regions from 7-10 days for infants with EOS, and 4-7 days for infants with no sepsis. Incidence of EOS ranged from 0.33 to 0.93 per 1000 live births between regions. The number of infants treated per EOS case varied 2-fold to 15-fold across regions (22-39) and units (7-113). All-cause mortality and EOS-associated mortality ranged across regions from 0.21 to 0.54 per 1000 live births and 0.0 to 34.9 (3 of 86 newborns) per 1000 infants with EOS.

Conclusions: This nationwide study revealed wide variations in antibiotic use and in the number of infants treated per EOS case. The results indicate a disproportionate antibiotic use in relation to the incidence of EOS. This emphasises the need for future efforts to minimise unwarranted antibiotic use.