Fetal pulmonary artery Doppler blood flow velocity measures and early infant lung function. A prospective cohort study.

BACKGROUND: Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function. OBJECTIVE: Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures. METHODS: In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (tPTEF/tE), tPTEF/tE <25th percentile, and tidal volume per kg body weight (VT/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions. RESULTS: The infants were born at median (min - max) 40.3 (35.6 - 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) tPTEF/tE was 0.39 (0.1) and the 25th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and tPTEF/tE, tPTEF/tE <25th percentile, or VT/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures. CONCLUSION: In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.

Predicting Skin Barrier Dysfunction and Atopic Dermatitis in Early Infancy.

BACKGROUND: Dry skin is associated with increased transepidermal water loss (TEWL), which has been found to precede atopic dermatitis (AD) in childhood. OBJECTIVE: We aimed to identify parental, prenatal, and perinatal predictive factors of dry skin, high TEWL, and AD at 3 months of age, and to determine if dry skin or high TEWL at 3 months can predict AD at 6 months. METHODS: From the Preventing Atopic Dermatitis and Allergies in children prospective birth cohort study, we included 1150 mother-child pairs. Dry skin, TEWL, and eczema were assessed at 3- and 6-month investigations. Eczema, used as a proxy for AD, was defined as the presence of eczematous lesions, excluding differential diagnoses to AD. High TEWL was defined as TEWL >90th percentile, equaling 11.3 g/m2/h. Potential predictive factors were recorded from electronic questionnaires at 18- and 34-week pregnancy and obstetric charts. RESULTS: Significant predictive factors (P < .05) for dry skin at 3 months were delivery >38 gestational weeks and paternal age >37 years; for high TEWL, male sex, birth during winter season, and maternal allergic disease; and for eczema, elective caesarean section, multiparity, and maternal allergic diseases. Dry skin without eczema at 3 months was predictive for eczema at 6 months (adjusted odds ratio: 1.92, 95% confidence interval: 1.21-3.05; P = .005), whereas high TEWL at 3 months was not. CONCLUSION: In early infancy, distinct parental- and pregnancy-related factors were predictive for dry skin, high TEWL, and AD. Dry skin at 3 months of age was predictive for AD 3 months later.

Allergic diseases and the effect of inhaled epinephrine in children with acute bronchiolitis: follow-up from the randomised, controlled, double-blind, Bronchiolitis ALL trial.

BACKGROUND: Although use of inhaled bronchodilators in infants with acute bronchiolitis is not supported by evidence-based guidelines, it is often justified by the belief in a subgroup effect in individuals developing atopic disease. We aimed to assess if inhaled epinephrine during acute bronchiolitis in infancy would benefit patients with later recurrent bronchial obstruction, atopic eczema, or allergic sensitisation. METHODS: In the randomised, double-blind, multicentre Bronchiolitis ALL trial, 404 infants with moderate-to-severe acute bronchiolitis were recruited from eight hospitals in Norway to receive either inhaled epinephrine or saline up to every second hour throughout the hospital stay. Randomisation was done centrally, and the two study medications (20 mg/mL racemic epinephrine or 0.9% saline) were prepared in identical bottles. The dose given depended on the infant's weight: 0.10 mL, less than 5 kg; 0.15 mL, 5-6.9 kg; 0.2 mL, 7-9.9 kg; and 0.25 mL, 10 kg or more; all dissolved in 2 mL of 0.9% saline before nebulisation. The primary outcome was the length of hospital stay. In this follow-up study, 294 children were reinvestigated at 2 years of age with an interview, a clinical examination, and a skin prick test for 17 allergens, determining bronchial obstruction, atopic eczema, and allergic sensitisation, on which subgroup analyses were done. Analyses were done by intention to treat. The trial has been completed and is registered at ClinicalTrials.gov (number NCT00817466) and EUDRACT (number 2009-012667-34). FINDINGS: Length of stay did not differ between patients who received inhaled epinephrine versus saline in the subgroup of infants who developed recurrent bronchial obstruction by age 2 years (143 [48.6%] of 294 patients; p(interaction)=0.40). However, the presence of atopic eczema or allergic sensitisation by the age of 2 years (n=77) significantly interacted with the treatment effect of inhaled epinephrine (p(interaction)=0.02); the length of stay (mean 80.3 h, 95% CI 72.8-87.9) was significantly shorter in patients receiving inhaled epinephrine versus saline in patients without allergic sensitisation or atopic eczema by 2 years (-19.9 h, -33.1 to -6.3; p=0.003). No significant differences were found in length of hospital stay in response to epinephrine or saline in children with atopic eczema or allergic sensitisation by 2 years (+16.2 h, -11.0 to 43.3; p=0.24). INTERPRETATION: Contrary to our hypothesis, hospital length of stay for bronchiolitis was not reduced by administration of inhaled epinephrine in infants who subsequently developed atopic eczema, allergic sensitisation, or recurrent bronchial obstruction. The present study does not support an individual trial of inhaled epinephrine in acute bronchiolitis in children with increased risk of allergic diseases. FUNDING: Medicines for Children Network, Norway.