Smoking in the family is most predictive of the development of childhood asthma in preterm babies <30 weeks gestation: Results of the Respiratory Outcomes Study 2 (RESPOS2)

Objectives: The Respiratory Outcomes Study 2 (RESPOS2) investigated the relationship between neonatal outcomes (specifically, chronic lung disease [CLD]) and environmental factors on the development of asthma and atopic outcomes at primary school age for preterm babies (PBs) <30 weeks gestational age (GA). Methods: The study included all surviving PBs <30 weeks GA admitted to the Neonatal Intensive Care Unit at Canberra Hospital, Australian Capital Territory between 2007 and 2009. Parents were sent a questionnaire regarding asthma and atopy symptoms when the PBs were aged 5–7 years old. Data were compared based on CLD status. Results: There were 103 PBs included in the study with a 68.9% response rate to the respiratory questionnaire (71/103). Of these PBs, 15/71 (21.1%) received a diagnosis of CLD. There were no significant differences with regards to asthma, hay fever or eczema in PBs either with or without CLD. The most significant predictor for the development of asthma was smoking in the family (Odds Ratio [OR]: 11.66, 95% Confidence Interval [CI]: 2.01–67.56) with a trend toward significance for family history of asthma (OR: 3.83, 95% CI: 0.85–17.25). Conclusion: The RESPOS2 has confirmed previous reports that CLD in PBs <30 weeks GA is not associated with the development of childhood asthma, hay fever or eczema. In our group of PBs, the strongest predictor of the development of asthma was smoking in the family.     

Paths of causal influence from prenatal inflammation and preterm gestation to childhood asthma symptoms

Introduction: Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. The aim was to investigate paths of assumed causality leading from foetal inflammatory response syndrome (FIRS) to asthma symptoms in preterms. Methods: Demographic, antenatal, delivery and outcome data were collected from 262 infants with less than 32 completed weeks of gestational age over a 10-year period in a prospective cohort study. The presence of symptoms of asthma beyond the age of 5?years was the primary outcome measure. The causal effect of FIRS on childhood asthma was tested with three different logistic regression models and two structural equation models (SEM). Results: FIRS (OR = 4.7) and subsequent chronic lung disease of prematurity (OR = 7.7) and early childhood wheezing (OR = 9.5) are the most important risk factors for development of asthma symptoms in children born with less than 32?weeks of gestational age. The path analysis showed that FIRS has a large direct (0.59), medium indirect (0.11) and large overall (0.70) effect on CLD; large negative direct effect on ECW (?0.34) and a large positive indirect effect (0.74), mediated by CLD. On the occurrence of asthma symptoms, FIRS has a medium negative direct effect (?0.18) and a medium positive indirect effect (0.26), mediated by CLD and ECW. Conclusion: Prenatal inflammation plays an important role in the development of chronic respiratory disturbances in preterm infants. This influence is mainly related to structural and developmental lung abnormalities initiated in utero as consequences of FIRS, resulting in CLD of prematurity, and overcoming the protective mechanisms of chorioamnionitis.     

Growth and differentiation factor 15 (GDF15) levels predict adverse respiratory outcomes in premature neonates

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved from 57 preterm infants at five time points, from birth until 36-weeks postmenstrual age (PMA). GDF15 levels were measured using ELISA in 114 samples. We performed two-sample t-test, correlation and linear regression, logistic regression, and mixed-effects linear models for statistical analysis, and significance was identified when p < 0.05. Contrary to our hypothesis, for every 1-week increase in gestational age at birth, the predicted GDF15 level decreased by 475.0 pg/ml (p < 0.001). Greater PMA was significantly associated with lower serum GDF15 levels (p < 0.001). Interestingly, higher GDF15 levels were associated with a longer need for mechanical ventilation (p = 0.034), prolonged respiratory support need (p < 0.001), and length of hospital stay (p = 0.006). In conclusion, in preterm infants, GDF15 levels show an inverse correlation with gestational age at birth, with higher levels in more preterm babies, and levels trend down postnatally. Furthermore, longitudinal GDF15 levels through 36 weeks PMA predict adverse respiratory outcomes in preterm infants.     

Early prediction of neonatal chronic lung disease: a comparison of three scoring methods.

A variety of postnatal therapies have been and will be evaluated for prevention or treatment of neonatal chronic lung disease (CLD). A simple method for early selection of the highest risk infants would optimize intervention trials. Our study compared a clinical scoring system for predicting neonatal CLD (defined at 36 weeks postconceptional age) with previous regression models developed by Sinkin et al. (Sinkin model) [Pediatrics 1990;86:728-736] and Ryan et al. (Ryan model) [Eur J Pediatr 1996;668-671] in two distinct populations. A respiratory failure score (RFS) was prospectively developed for infants at <32 weeks of gestation admitted to the Wilford Hall Medical Center from January 1990-December 1992. Logistic regression modeling identified three independent predictors of CLD: gestation, birth weight, and RFS. Applying a modified RFS score (to include gestation and birth weight), the RFS, Sinkin, and Ryan models were compared among high-risk infants admitted to Wilford Hall from January 1993-December 1995, and to Crawford Long Hospital (Atlanta, GA) from January 1993-December 1994. Predictive values, sensitivity, specificity, and receiver operating characteristic (ROC) curves were determined for the primary outcome variable: CLD at 36 weeks of corrected gestation. Of 248 infants at <32 weeks admitted to Wilford Hall, 220 survived >7 days. Thirty of 31 (97%) infants diagnosed with CLD were <29 weeks or < or =1,000 g at birth. Despite important demographic and treatment differences between the study populations, similar ROC curves were found for each scoring method when individually evaluated among the three study groups. The RFS method at 72 h demonstrated the greatest area under the ROC curve for prediction of neonatal CLD in the groups as a whole. Application of the RFS method for early prediction of neonatal CLD at age 72 h should improve patient selection for early prevention trials.     

Exhaled nitric oxide at school age in prematurely born infants with neonatal chronic lung disease

Prematurely born infants with neonatal chronic lung disease (CLD) have increased respiratory morbidity and bronchial obstruction at school age. To evaluate the possible inflammatory basis of lung function abnormalities, we studied 40 children, 7.5-9.6 years of age, born very prematurely (birth weights, 600-1,575 g) and 14 nonatopic term-born controls, using flow-volume spirometry and exhaled nitric oxide (eNO) measurements. In children born prematurely, eNO was significantly higher in atopics than in nonatopics (respective means, 14.8 vs. 6.3 ppb, P = 0.02). Nonatopic prematurely born infants did not differ significantly from controls (means, 6.3 vs. 6.4 ppb, P = ns). Of the 27 nonatopic children not on regular glucocorticoid inhalations, 9 had a history of CLD. Spirometry indicated bronchial obstruction and values that were significantly lower in prematurely born infants with or without CLD than in controls, and they were lower in the CLD than the non-CLD group. However, no significant differences were observed in eNO levels between CLD, non-CLD, and control groups (means, 6.8, 5.9, and 6.4 ppb, P = ns). In nonatopic schoolchildren born very prematurely and with a history of CLD, we found no evidence of airway inflammation associated with increased eNO concentrations. Neither were eNO levels associated with severity of chronic lung disease, as determined by conventional lung function tests. eNO levels were higher in atopic children born prematurely than in controls.     

Lung function and exhaled nitric oxide levels in infants developing chronic lung disease

Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.     

Epidermal growth factor in the lungs of infants developing chronic lung disease.

Growth factors important to lung growth and fibrosis have been poorly studied in chronic lung disease (CLD) of prematurity. Epidermal growth factor (EGF) promotes epithelial cell maturation, and vascular endothelial growth factor (VEGF) is important in angiogenesis. The concentration of these growth factors was determined in 111 bronchoalveolar lavage fluid (BALF) samples from 35 ventilated infants: 13 developed CLD (median gestation 27 weeks, birthweight 820 g), 16 developed and recovered from respiratory distress syndrome (RDS) (31 weeks, 1,415 g) and six control infants (33 weeks, 2,075 g) were ventilated for nonpulmonary reasons. At birth, EGF in BALF from the CLD and RDS infants was lower than in the control infants (control versus CLD, 7.3 versus 0.0 pg x mL(-1), p<0.01; control versus RDS, 7.3 versus 5.0, p=0.08). EGF increased in all groups with a more rapid increase in control infants. A close relationship was noted between BALF EGF and gestational age (R=0.73). VEGF was undetectable at birth but increased at a similar rate in all three groups and did not correlate with gestation. In conclusion, these data suggest that epidermal growth factor is closely correlated to gestation and that it may predispose preterm infants to develop chronic lung disease.     

Transcutaneous oxygen tension measurements during methacholine challenge of prematurity in infants with chronic lung disease

Chronic lung disease (CLD) of prematurity may be caused by a number of insults during mechanical ventilation, including barotrauma and hyperoxia. To evaluate bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we measured changes in transcutaneous oxygen tensions (tcPO₂) during methacholine inhalation challenge. Twelve infants with CLD and 22 age-matched children without respiratory diseases were enrolled in this study (ages—5 to 36 months; mean age—16.2 months). Serial doses of methacholine were doubled until a 10% decrease in tcPO₂ from baseline was reached. The cumulative dose of methacholine inhaled by the time tcPO₂ had been reached (Dmin-PO₂) was considered to represent the dose at which reactivity to methacholine (RO₂meth) had occurred. In the CLD group, Dmin-PO₂ (3.50 ± 0.1 log.milli-units) was significantly lower than in the preterm control infant group (4.31 ± 0.2 log·milli-units) and the term infant group (4.21 ± 0.1 log.milli-units) (P = 0.004, P < 0.001). Dmin-PO₂ in the preterm control infant group was not significantly different than in the term infant group (P > 0.5). These results suggest that infants who require additional therapeutic oxygen and mechanical ventilation during the early months of life are at risk of developing early-onset, long-lasting respiratory disease that is related to an acquired BHR. Pediatr Pulmonol. 1998; 25:338–342. © 1998 Wiley-Liss, Inc.     

The red cell distribution width (RDW): Value and role in preterm,IUGR (intrauterine growth restricted), full-term infants

Objective

To measure the red cell distribution width (RDW) ranges at birth and to evaluate potential association with typical neonatal diseases: patent of the ductus arteriousus (PDA), bronchopulmonary dysplasia (BPD), and late-onset sepsis (LOS) mortality.

Methods

Forty-six full-term, 41 preterm, and 35 intrauterine growth restricted (IUGR) infants participated in this retrospective, observational study. RDW was measured before 3 days of life (T0) in all infants, and at first month of life (T1) in preterm/IURG patients.

Results

RDW% mean (standard deviation) at T0 was: 15.65 (1.18) in full-term newborns; 17.7 (2.06) in preterm; 17.45 (1.81) in IUGR. A negative correlation (r = ?0.51; P < 0.001) between RDW and gestational age was found. RDW at T1 was: 17.25 (2.19) in the preterm group; 17.37 (2.56) in IUGR group. Fourteen preterm infants reported: 12 PDA, 5 LOS, 4 BPD, and 3 died; 10 IUGR infants had: 4 PDA, 6 LOS, 3 BPD, and 1 died.

RDW of IUGR infants suffering from those pathologies was not statistically different compared with unaffected infants, while preterm newborns with pathologies reported higher RDW: PDA vs. PDA absent: P = 0.008 at T0; P < 0.002 at T1. BPD vs. BPD absent: P < 0.005 at T1. LOS vs. LOS absent: P < 0.005 at T0.

RDW in preterm/IUGR population was associated with early mortality, T0: dead 21.2 (2.7) vs. alive 16.7 (1.7), P < 0.0001.

Conclusion

RDW and gestational age at birth were negatively correlated. High RDW resulted to be an indication of risk for critical newborns. This parameter can be inexpensively and routinely verified and further studies are required to confirm its prognostic role in neonatal pathologies.     

Functional residual capacity and passive compliance measurements after antenatal steroid therapy in preterm infants

Studies in preterm animal models have shown that antenatal corticosteroids enhance lung maturation by improving a variety of physiologic variables, including lung volumes. Changes in lung volume of preterm infants treated with a full course of antenatal steroids have not been investigated. We hypothesized that a full course of antenatal steroids would significantly increase functional residual capacity (FRC) in treated vs. untreated preterm infants. The objective of our study was to compare FRC and respiratory mechanics in steroid treated vs. untreated preterm infants. FRC and passive respiratory mechanics were prospectively studied within 36 hr of life in 20 infants (25-34 weeks of gestation) who had received a full course of antenatal steroids and in 20 matched untreated preterm infants. FRC was measured with the nitrogen washout method, and respiratory mechanics with the single-breath occlusion technique. Preterm infants who received steroids (n = 20; mean birth weight = 1,230 g; gestational age = 28.8 weeks) had a significantly higher FRC (29.5 vs. 19.3 mL/kg; P < 0.001) than untreated infants (n = 20; birth weight = 1,202 g; gestational age = 28.5 weeks). Passive respiratory system compliance was also increased in treated vs. untreated infants (P < 0.05). In conclusion, FRC and passive respiratory system compliance were significantly improved in preterm infants (25-34 weeks gestation) treated with a full course of antenatal steroids, compared to matched untreated infants. Although this study was not randomized, it confirms that antenatal steroids have important effects on pulmonary function that may contribute to a decreased risk of respiratory distress syndrome in treated preterm infants.     

Assessment of passive respiratory compliance in healthy preterm infants: A critical evaluation

The airway occlusion techniques for assessing passive respiratory mechanics have become well established methods in fullterm neonates and older infants. The single breath technique (SBT) is frequently used for assessing lung function in intubated infants on neonatal intensive care units. However, less is known about the reliability of these quick and noninvasive techniques in healthy preterm infants. The aim of this study was to evaluate these methods in healthy unintubated preterm infants to facilitate both establishment of reference values and more meaningful interpretation of lung function assessments in the neonatal unit. Forty-seven studies were attempted in 31 healthy preterm infants (gestational age 29–36 weeks; body weight 1.88 ± 0.28 kg; mean ± SD) during the first 2 weeks of life, using both the multiple occlusion technique (MOT) and the SBT. Whereas technically acceptable respiratory system compliance (Crs) data from either the MOT or the SBT were obtained on 37 occasions in 25 infants, satisfactory results from both techniques were achieved only on 22 occasions. In these infants mean ± SD Crs was 28.1± 5.2 mL kPa^?1 when assessed by MOT and 29.1± 5 6.0 mL kPa^?1 when using the SBT. The mean difference between technically satisfactory paired Crs values obtained with MOT and SBT was less than 5% (range, +28 to ?18%). By contrast, in infants in whom data were invalidated as a result of expiratory airflow braking, failure to relax or instability of the end-expiratory level, gross discrepancies occurred between the techniques. In conclusion, assessment of passive respiratory compliance is feasible in healthy, unintubated preterm infants, but strict criteria for quality control should be applied to avoid gross errors in the results. Ideally, passive respiratory mechanics should be assessed using both MOT and SBT in order to increase confidence in the reported results. © 1993 Wiley-Liss, Inc.     

Lung function in 6-20 month old infants born very preterm but without respiratory troubles.

Lung function results of 21 healthy infants born very prematurely are reported. The median gestational age was 29 weeks, but none had developed respiratory distress or required any form of respiratory support in the neonatal period. Lung function was assessed by measurements of thoracic gas volume (TGV) and airway resistance (Raw) plethysmographically, and of functional residual capacity (FRC) using a helium gas dilution technique. Two separate measurements were made between 6 and 20 months of age; all infants were measured once in the first and once in the second year of life. Regression equations were calculated for TGV, Raw, and FRC related to weight, height, and postnatal age. These data provide a new set of values for very preterm infants, in part small for gestational age, without neonatal respiratory trouble.     

Development of Lung Function in Preterm Infants During the First Two Years of Life

IntroductionIt remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size.AimTo assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period.MethodsThis observational longitudinal study assessed lung function in 74 preterm (30 + 0 to 35 + 6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF_25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age.ResultsLung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV_0.5 and forced expiratory flows was seen in preterm infants.ConclusionWhen compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.     

Oral-motor dysfunction at 10 months corrected gestational age in infants born less than 37 weeks preterm

Feeding difficulties are common in preterm infants. These may be associated with inadequate dietary intake, poor growth, and parental anxiety. Oral-motor dysfunction has been observed in preterm infants during sucking and the early stages of weaning but has not been rigorously studied in later infancy when eating a range of food consistencies. We aimed to establish if oral-motor dysfunction during feeding occurs in preterm infants in later infancy and to explore the relationships with specific neonatal risk factors: gestational age at birth, prolonged supplementary oxygen requirement, and delay in establishing full oral feeding. Infants born less than 37 weeks gestational age were evaluated once at 10 months corrected gestational age using a validated feeding assessment (Schedule for Oral Motor Assessment). Fifteen infants were enrolled (9 males, 6 females; median gestational age at birth = 33 weeks, range = 25–36 weeks; median birth weight = 1890 g, range = 710–2950 g). Oral-motor dysfunction was observed in three infants all born after 31 weeks gestation. No relationship was found with the neonatal risk factors. This study indicates that oral-motor dysfunction may occur in later infancy and is not easily predicted from specific neonatal risk factors. Further study is required to evaluate the true prevalence and the health implications of oral-motor dysfunction in this population in later infancy.

Antenatal exposure to nonsteroidal anti‐inflammatory drugs and risk of neonatal hypertension

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are used as tocolytics, which are medications that suppress uterine contractions for preterm birth prevention. Their effect on cerebral/systemic vascular beds poses the question of whether antenatal NSAID exposure is associated with neonatal hypertension. We performed a retrospective case‐control study in a tertiary neonatal intensive care unit, including 40 hypertension cases (hospitalized neonates ≥ 35 weeks with systolic BP > 100 mm Hg on three consecutive days) compared to 134 controls matched by gestational age at delivery, plurality, and delivery date. Cases and controls were compared by antenatal NSAID exposure, other common tocolytics, and maternal/neonatal characteristics and complications. Multivariable logistic regression was used to estimate the odds of hypertension among those with prenatal exposure to NSAIDs versus those without exposure. Newborns with hypertension had a lower gestational age at delivery and increased incidence of neonatal complications, including respiratory distress syndrome, bronchopulmonary dysplasia, surfactant administration, longer duration of ventilation, and history of umbilical artery catheterization. Days of indomethacin exposure were positively associated with greater odds of neonatal hypertension (OR 1.17 [1.00 to 1.38], P = 0.055), even after adjustment for other factors associated with neonatal hypertension. Newborns with hypertension were less likely to have been exposed to calcium channel blockers as a tocolytic. The results of our study suggest an association between prenatal exposure to nonsteroidal anti‐inflammatory drugs and neonatal hypertension. Furthermore, our data suggest that prenatal calcium channel blocker exposure may protect against the development of neonatal hypertension. Future multicenter studies are needed to understand the risks of tocolytics and subsequent consequences in preterm infants.     

General movement assessment is correlated with neonatal behavior neurological assessment/cerebral magnetic resonance imaging in preterm infants

To explore the relationship between general movements (GMs) and neonatal behavior neurological assessment (NBNA)/cerebral magnetic resonance imaging (MRI) in preterm infants.Forty preterm infants were examined with GMs assessment before gestational age of 40 weeks; NBNA was performed at the age of 40 weeks; cerebral MRI was performed at the age of 42 weeks.Our experiment showed that preterm infants with poor GMs scores are more likely to have low NBNA scores (P = .001); preterm infants with abnormal cerebral MRI are more likely to have low NBNA scores (P = .002); preterm infants with poor GMs scores are more likely to have abnormal cerebral MRI (P = .012).GM assessment is correlated with NBNA and MRI results in preterm infants for neurological development.     

Maturation of antroduodenal motor activity in preterm and term infants

Previous studies have shown that duodenal motility patterns differ in preterm and term infants, but antral motor activities were not compared. Using a validated, lowcompliance, continuous-perfusion, neonatal manometric system, antral and duodenal motility was studied in 19 preterm and nine term infants. Antral motility consisted of isolated single contractions and clustered phasic contractions in term and preterm infants. There were no differences in the occurrence or amplitude of antral activity between the two groups of infants. Thus, there was no change of antral motor activity with advancing gestational age. As has been shown in other previous studies, however, intestinal motor characteristics were more immature in preterm than term infants; clustered phasic contractions occurred more frequently (P<0.02) and were of shorter duration (P<0.02) and lower amplitude (P<0.005). Duodenal clusters were significantly less common, while their amplitudes were significantly increased with increasing gestational age. The proportion of antral clusters that were temporally associated with duodenal activity was significantly lower in preterm infants than in term infants (P<0.001). Moreover, the degree of association of antral and duodenal activity increased significantly with gestational age (r=0.5,P=0.006). These data show that fasting antral motor activityper se is comparable in preterm and term infants; they also suggest that the temporal association of antral and duodenal activity develops in association with progressive changes in duodenal motor activity in the preterm infant.This word was supported by grant number HD24558 from National Institutes of Health.     

Predictive value of measurements of respiratory mechanics in preterm infants with HMD

Conventional methods for measuring respiratory mechanics model the respiratory system as a single compartment. The interrupter technique allows the respiratory system to be considered as a two compartment model with “flow resistance” of the conducting airways (Pinit), calculated from the initial pressure drop (Pinit), considered separately from Pdiff, as a measure of the viscoelastic properties of the lung and chest wall and any pendelluft present. The pulmonary mechanics of 50 intubated and mechanically ventilated preterm infants (≤1500 g) were studied during the first week of life using conventional methods and the interrupter technique to determine whether it was possible to predict which infants would develop bronchopulmonary dysplasia (BPD). Pulmonary mechanics of preterm infants intubated and ventilated for apnea of prematurity were also studied. The dynamic compliance of the respiratory system (C_rsdyn) was significantly lower on day 1 (P<0.001) and during the first week of life in the infants with HMD who developed BPD (ANOVA, P<0.0001). There was no significant difference in the respiratory system resistance (R_rs), Rinit, or Pdiff between BPD and no-BPD groups. However, Pdiff was significantly higher in infants with HMD, regardless of the outcome, when compared to the infants ventilated for apnea of prematurity. This suggests that the pathology of HMD is distal to the conducting airways and significantly alters the viscoelastic properties of the lung on day 1. Using stepwise logistic regression, C_rsdum on day 1 and birth weight or gestational age were significant independent predictors of the development of BPD, correctly classifying 92% of infants. Due to the correlation between birth weight and gestational age (r = 0.72, P<0.0001). only one of these variables was necessary in the prediction model. In conclusion, C_rsdyn is a better independent predictor of the development of BPD in preterm infants with HMD than gestational age or birth weight. Pediatr Pulmonol. 1993; 16:116–123. © 1993 Wiley-Liss, Inc.     

Two-year neurodevelopmental outcomes of preterm infants who received red blood cell transfusion

BackgroundStudies aimed at reducing neonatal anaemia or transfusing higher blood volumes did not find improvement in neurodevelopmental function at two years of age. This study investigated the relationship between the receipt, timing, and number of red blood cell (RBC) transfusions and neurodevelopmental outcomes among preterm infants.Materials and methodsThis is a retrospective review of preterm infants (gestational age <34 weeks) with a full neurodevelopmental assessment at 18–36 months corrected age from October 2008 to September 2020. Bayley Scales of Infant and Toddler Development, third edition and the Modified Checklist for Autism in Toddlers were collected. Multivariable regressions were used to evaluate neurodevelopmental outcomes.Results654 preterm infants were evaluated with a mean follow-up of 25 months. 295 infants (45%) received a total of 1,322 blood transfusions. After adjustment for gestational age, baseline morbidity, and socioeconomic status, receipt of RBC transfusion was associated with decreased two-year cognitive and motor function, but not language (p=0.047, 0.025, and 0.879, respectively). There was no significant difference in outcomes between receipt of transfusion in the first week of life compared to after. Number of transfusions was associated with decreased cognitive, language, and motor function (all p<0.001), and increased likelihood to develop severe neurodevelopmental impairment (adjusted-odds ratio, 1.09; 95% confidence interval, 1.03–1.15; p=0.004).DiscussionOur study demonstrates an association between RBC transfusion and lower cognitive and motor outcomes at two-years after adjustment for prematurity and illness at birth. Increasing number of transfusions worsened neurodevelopmental outcomes.