Neonatal FeNO, risk factors, and respiratory morbidity in infants: A cohort study.

BACKGROUND: Respiratory symptoms in infancy are more common in premature infants. Nitric oxide (NO) is involved in prenatal and neonatal lung development. Measurement of exhaled NO is easy and well-tolerated by neonates. We investigated whether neonatal exhaled NO can be used to predict subsequent respiratory symptoms. Furthermore, we sought to determine prenatal and postnatal factors associated with increased respiratory symptom risk during the first year of life in premature and mature infants. METHODS: Tidal fractional exhaled NO (FeNO) was measured in a birth cohort (n = 135) of premature and mature infants, up to six times during the first month of life. Primary outcomes were troublesome respiratory symptoms (TRS) and doctor-diagnosed asthmatic bronchitis (AB) at 1 year of age. FINDINGS: The correlation between FeNO and TRS changed significantly in an age-dependent pattern in moderately premature infants (p = .02). Moderately premature infants with a low FeNO of 2 ppb on postnatal Day 3 had a 48% (95% confidence interval [CI]: 17%-80%) probability of TRS, compared with a probability of 12% (95% CI: 1%-64%) for otherwise similar infants with a FeNO of 11 ppb. Respiratory syncytial virus infection and parental smoking significantly increased the TRS risk in premature infants. Parental asthma and maternal antibiotic use during pregnancy significantly increased the TRS risk in mature infants. INTERPRETATION: An age-specific association between neonatal FeNO and respiratory symptoms was seen in moderately premature infants. TRS risk was associated with postnatal factors in premature and prenatal factors in mature infants.

Exhaled nitric oxide in premature and mature infants during the first months of life.

AIM: In this review, we aim to describe how exhaled Nitric Oxide(NO) changes during the first months of life in premature and mature infants. METHOD: Review of the literature up to August 2020, on online, tidal breathing NO measurements in unsedated infants. The association between Fractional exhaled NO(FeNO) values, postnatal age, and prematurity was analysed using linear mixed modeling and Spearman's rank correlation. RESULTS: Median FeNO during the first months of life was 5.9 and 8.5 ppb in premature and mature infants, respectively. The linear mixed model analysis showed a significant effect of postnatal age on FeNO (p = 0.007). CONCLUSION: Our study suggests that FeNO is higher in mature infants than premature infants, and FeNO increased with postnatal age at approximately the same pace in both groups.

Tidal breath eNO measurements in a cohort of unsedated hospitalized neonates-A method validation.

AIM: Exhaled Nitric oxide (eNO) is an inflammatory marker. In 2002 Hall et al. [J Appl Physiol. 92:59-66] established an infant eNO measurement method, fulfilling four criteria of feasibility: simple, non-invasive, without impact on the natural breathing pattern, and accounting for flow by NO output (V'NO). Although tidal breathing is accepted as an eNO measurement method in uncooperative patients, it is seldom used outside research labs. The variability and lack of validated methods have restrained from exploring the area in preterm and term neonates the last years. This study aimed to validate clinically feasible longitudinal online tidal eNO and V'NO in a real-life birth cohort of un-sedated, hospitalized preterm, and term neonates. METHOD: We included 149 newborns, GA 28-42 weeks. Each scheduled for six repeated, non-invasive, on-line eNO measurements with Ecomedics CLD 88sp and NO-free air. We used three 60-second-eNO measurements. The method was adapted to fit preterm and term neonates with unstable respiration, without excluding sighs and surrounding breaths. RESULT: Protocol measurements with a maximum mutual difference of 1 ppb succeeded in 85-99%, increasing with postnatal age. We performed mixed model analyses in three hierarchical measurement levels. Despite the irregular breathing of newborns, the predictions of individual eNO levels in the average infant was a 0.05 SD. Exhaled NO was flow-dependent (P = 0.028); V'NO but not eNO was associated with preterm birth (P < 0.001) and >24 h CPAP treatment (P = 0.0316). CONCLUSION: We validated clinically, non-invasive, online eNO measurements in neonates. The method was well tolerated and exhibited low subject-specific-prediction-variance and high success rates.