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

Background: Milk curd obstruction (MCO), in which milk becomes inspissated, is a rare, serious, complication of preterm birth. Case reports implicate male sex and bovine-derived human milk fortifier (HMF) use as predisposing factors. We investigated this through a case-control study.

Methods: MCO cases in the Starship Child Health neonatal database between 2008 and 2020 were matched with controls in a 1:2 ratio based on gestational age (±1 week), birth weight (±200 g) and date of birth (±1 month). Data were analysed using the Student's t-test, Mann-Whitney U-test or χ² test as appropriate. Data are median (IQR) or n (%).

Results: Of 20 MCO cases, gestation was 26.1 (24.5-28.1) weeks, birth weight was 822 (713-961) g, 15 (75%) were male. 40 controls were well-matched for gestation (26.1 (24.8-27.9) weeks) and birth weight (849 (690-1066) g) but only 18 (45%) were male (p=0.05). MCO occurred at 21 (15-33) days; 6 (30%) cases died compared with 3 (7.5%) controls (p=0.06). HMF was commenced at 243 (150-309) hours in cases and 224 (172-321) hours in controls (p=0.95); full-fortification (manufacturer's recommended dose) was achieved in 8 (40%) cases and 27 (68%) controls (p=0.08). In cases, MCO occurred 10 (7-17) days after commencing HMF. Medically/surgically-managed gut pathology occurred in 7 (35%) cases prior to MCO but in no controls (p<0.001).

Conclusions: Our data support male sex but not HMF use as a predisposition to MCO. Evidence of prior medical/surgical gut pathology may be a premonition for MCO; however, further research is required to confirm this.

Less invasive surfactant administration (LISA) is an increasingly popular technique to deliver surfactant to spontaneously breathing preterm infants with respiratory distress syndrome. The optimal method of alleviating the pain and discomfort associated with LISA, either pharmacological or non-pharmacological, while maintaining spontaneous respiration remains unclear. There is limited evidence to guide clinicians, resulting in wide variations in practice. The aim of this article is to summarise the current knowledge and evidence gaps regarding the use of premedication prior to LISA.

Background: Prematurity is a significant risk for bronchopulmonary dysplasia related pulmonary artery pressure.

Objective: To determine the association between pulmonary artery pressure in the early days of life and the development of bronchopulmonary dysplasia or mortality.

Methods: This prospective observational cohort study included infants born at <32 weeks and weighing <1500 g. Pulmonary artery pressure was measured between postnatal days 3 and 7. Pulmonary hypertension was defined as systolic pulmonary artery pressure ≥40 mm Hg or systolic pulmonary artery pressure/systolic blood pressure >0.5 (pulmonary hypertension criterion-1). Infants were categorised into pulmonary hypertension and non-pulmonary hypertension groups. The primary endpoint was bronchopulmonary dysplasia or mortality. Receiver operating characteristic analysis established a new threshold value for predicting bronchopulmonary dysplasia or mortality (pulmonary hypertension criterion-2). Infants were reanalysed according to new criteria.

Results: A total of 329 infants were included in this study. Moderate-to-severe pulmonary hypertension was identified in 24% (n=79) of the infants. The pulmonary hypertension group exhibited a significantly lower gestational age, lower birth weight and a higher incidence of small for gestational age. Systolic pulmonary artery pressure >25 mm Hg or systolic pulmonary artery pressure/systolic blood pressure >0.35 was defined as the pulmonary hypertension criterion-2. Logistic regression analysis identified pulmonary hypertension criterion-2 as an independent risk factor for moderate-to-severe bronchopulmonary dysplasia or mortality (OR 2.67, 95% CI 1.3 to 5.51, p<0.01).

Conclusion: Pulmonary artery pressure exceeding 25 mm Hg in the early days of life may be considered a potential risk factor for bronchopulmonary dysplasia or mortality.

Objective: This study investigates whether and to what extent cerebral injury is associated with bilateral blindness in extremely preterm infants, which has been attributed mainly to retinopathy of prematurity (ROP).

Design: Multicentre analysis of children born from 1994 to 2021 at gestational age 22 0/7 to 28 6/7 weeks with follow-up at 18-26 months. Logistic regression examined the adjusted association of bilateral blindness with severe ROP and/or cerebral injury among extremely preterm infants.

Exposures: Severe ROP and cerebral injury, the latter defined as any of the following on cranial imaging: ventriculomegaly; blood/increased echogenicity in the parenchyma; cystic periventricular leukomalacia.

Main outcome measures: Bilateral blindness, defined as a follow-up examination meeting criteria of 'blind-some functional vision' or 'blind-no useful vision' in both eyes.

Results: The 19 863 children included had a mean gestational age of 25.6±1.7 weeks, mean birth weight of 782±158 g and 213 (1%) had bilateral blindness. Multiplicative interaction between ROP and cerebral injury was statistically significant. For infants with only severe ROP (n=3130), odds of blindness were 8.14 times higher (95% CI 4.52 to 14.65), and for those with only cerebral injury (n=2836), odds were 8.38 times higher (95% CI 5.28 to 13.28), compared with the reference group without either condition. Risks were not synergistic for infants with both severe ROP and cerebral injury (n=1438, adjusted OR=28.7, 95% CI 16.0 to 51.7, p<0.0001).

Conclusions: In a group of extremely preterm infants, severe ROP and cerebral injury were equally important risk factors for blindness. Besides ROP, clinicians should consider cerebral injury as a cause of blindness in children born extremely preterm.

Trial registration number: NCT00063063.

ObjectiveGlobally, demand for donor human milk (DHM) is increasing with WHO guidelines recommending DHM as the first line nutrition for premature infants in the absence or shortfall of maternal milk. Policymakers and clinicians currently have limited knowledge regarding costs incurred by human milk banks (HMBs) making the planning and resourcing of these services challenging. This study aimed to evaluate costs in a national network of HMBs in the UK.

Design and setting: All 14 UK HMBS were invited to complete a bottom-up microcosting survey from 1 April 2021 to 31 March 2022 covering four key areas: Staffing, equipment, donor screening and incidental costs. Total annual salary costs included on-costs (ie, national insurance, pensions), qualifications, overheads (ie, non-staff costs) and capital overheads. The annual equivalent costs for each equipment item were based on the total cost over its useful life and discounted at 3.5%.

Results: 10 out of 14 milk banks provided responses with more complete datasets returned by larger milk banks. Staffing costs ranged from £24 983 to £476 194 (n=9, mean: £159 798) and considerable expertise was provided voluntarily or from non-costed staffing. Other costs included equipment (n=7, range: £2600-£51 453, mean: £19 279), donor screening (n=6, range: £925-£38 057, mean: £18 570), incidentals (n=6, range: £650-£109 996, mean: £23 774). The total annual cost of operating a milk bank annually was £202 719 (range, £27 583-£675 699) to provide between 205 and 3495 litres of DHM. The cost per litre averaged £173.49 (range, £95.94-£274.88).

Conclusions: The average cost of DHM is currently higher than current cost recovery tariffs and this study likely under-represents total costs. This study provides useful benchmarking data for future economic analyses, trial development and service planning.

Objective: To investigate the relationship between the fraction of fetal haemoglobin (HbF(%)) and oxygen requirement as determined by the fraction of inspired oxygen (FiO₂) and alveolar-arterial gradient (A-a gradient). Increased alveolar exposure to oxygen may explain the association between decreased HbF(%) and the development of bronchopulmonary dysplasia (BPD).

Design: Longitudinal, retrospective, observational study.

Setting: Tertiary-level neonatal intensive care unit, referral centre for southern Sweden.

Patients: Four hundred forty very preterm infants born before gestational week 30, 2009-2015.

Intervention: Regular clinical practice.

Main outcome measures: The FiO₂ and A-a gradient were determined at the time-point of 10 015 arterial blood gas analyses obtained during postnatal days 1-7. The relationship between HbF(%) and FiO₂ and A-a gradient and the modifying influence of other factors affecting haemoglobin oxygen affinity were evaluated.

Results: We found a significant relationship between a low fraction of HbF and an increase in FiO₂ and A-a gradient, respectively. These relationships remained significant after adjusting for pH, pCO₂, postnatal age, gestational age and sex.

Conclusion: These high-resolution data show that decreased HbF(%) during the first postnatal week is associated with increased FiO₂ and A-a gradient in very preterm infants. Increased alveolar exposure to oxygen and resulting oxidative stress may, at least partly, explain the previously reported associations between decreased HbF, blood transfusions and the development of BPD in preterm infants.

Objective: Reports of hyperinsulinism typically focus on infants managed by highly specialised services. However, neonates with hyperinsulinism are initially managed by neonatologists and often not referred to specialists. This study aimed to characterise the diversity in presentation and management of these infants.

Setting: Level 3 neonatal intensive care.

Patients: Neonates with hyperinsulinism, defined as blood glucose <2.8 mmol/mL and insulin level >6 pmol/L.

Design: 7-year retrospective study (January 2015-December 2021).

Results: 99 cases were identified: severe-treated with diazoxide (20%), moderate-clinically concerning hyperinsulinism not treated with diazoxide (30%), mild-biochemical hyperinsulinism (50%). Birth weight z-score was -1.02±2.30 (mean±SD), 42% were preterm, but neither variable correlated with clinical severity. The severe group received a higher concentration of intravenous glucose (27±12%) compared with the moderate (15±7%) and mild (16±10%) groups (p<0.001). At diagnosis, the intravenous glucose intake was similar in the severe (7.43±5.95 mg/kg/min) and moderate (5.09±3.86 mg/kg/min) groups, but higher compared with the mild group (3.05+/2.21 mg/kg/min) (p<0.001). In the severe group, term infants started diazoxide earlier (9.9±4.3 days) compared with preterm (37±26 days) (p=0.002). The national congenital hyperinsulinism service was consulted for 23% of infants, and 3% were transferred.

Conclusions: This study highlights the diversity in clinical presentation, severity and prognosis of neonatal hyperinsulinism, irrespective of birth weight and gestational age. More infants were small rather than large for gestational age, and the majority had transient hyperinsulinism and were not referred to the national centre, or treated with diazoxide. Further research is required to understand the breadth of neonatal hyperinsulinism and optimal management.