Impact of ethnicity and extreme prematurity on infant pulmonary function.

The impact of birth before 27 completed weeks of gestation on infant pulmonary function (PF) was explored in a multi-ethnic population in comparison to more mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung volume (FRCpleth ) and forced expired volume (FEV0.5 ) were obtained at ∼12 months post-term age in 52 extremely preterm (EP) infants (median [range] gestational age [GA]: 26 [23-27] weeks; 40% White mothers; 79% with BPD), 41 PTC (GA:35 [30-36] weeks; 37% White mothers) and 95 fullterm infants (GA:40 [37-42] weeks; 86% White mothers). Using reference equations based on identical equipment and techniques, results were expressed as z-scores to adjust for age, sex and body size. FEV0.5 was significantly lower in EP infants when compared with PTC (mean difference [95% CI]: -1.02[-1.60; -0.44] z-scores, P < 0.001), as was forced vital capacity (FVC) but there were no significant differences in FRCpleth or FEV0.5 /FVC ratio. FEV0.5 , FVC, and FEV0.5 /FVC were significantly lower in both preterm groups when compared with fullterm controls. On multivariable analyses of the combined preterm dataset: FEV0.5 at ∼1 year was 0.11 [0.05; 0.17] z-scores higher/week GA, and 1.28 (0.49; 2.08) z-scores lower in EP infants with prior BPD. Among non-white preterm infants, FEV0.5 was 0.70 (0.17; 1.24) z-scores lower, with similar reductions in FVC, such that there were no ethnic differences in FEV0.5 /FVC. Similar ethnic differences were observed among fullterm infants. These results confirm the negative impact of preterm birth on subsequent lung development, especially following a diagnosis of BPD, and emphasize the importance of taking ethnic background into account when interpreting results during infancy as in older subjects. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc

Impact of Ethnicity and Extreme Prematurity on Infant Pulmonary Function

Summary. The impact of birth before 27 completed weeks of gestation on infant pulmonary function (PF) was explored in a multi-ethnic population in comparison to more mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung volume (FRC pleth ) and forced expired volume (FEV 0.5 .44] z-scores, P &lt; 0.001), as was forced vital capacity (FVC) but there were no significant differences in FRC pleth or FEV 0.5 /FVC ratio. FEV 0.5 , FVC, and FEV 0.5 /FVC were significantly lower in both preterm groups when compared with fullterm controls. On multivariable analyses of the combined preterm dataset: FEV 0.5 at $1 year was 0.11 [0.05; 0.17] z-scores higher/week GA, and 1.28 (0.49; 2.08) z-scores lower in EP infants with prior BPD. Among nonwhite preterm infants, FEV 0.5 was 0.70 (0.17; 1.24) z-scores lower, with similar reductions in FVC, such that there were no ethnic differences in FEV 0.5 /FVC. Similar ethnic differences were observed among fullterm infants. These results confirm the negative impact of preterm birth on subsequent lung development, especially following a diagnosis of BPD, and emphasize the importance of taking ethnic background into account when interpreting results during infancy as in older subjects

The EPICure study : growth and blood pressure at 6 years of age following extremely preterm birth

Background: Preterm children are at risk for reduced growth in early childhood, which may predispose them to later changes in blood pressure. We studied growth and blood pressure (BP) in extremely preterm (EP) children at age 6 years. Methods: We evaluated children who were born at 25 completed weeks of gestation or less in the United Kingdom and Ireland in 1995 when they reached early school age. Children underwent standardized assessments, including auxology and sitting blood pressure. Results: Of 308 surviving children, 241 (78 percent) were assessed at a median age of 6 years 4 months; 160 full term classmates acted as a comparison group. Compared to classmates, EP children were 1.2 standard deviations (SD) lighter, 0.97SD shorter, BMI was 0.95SD lower and head circumference 1.3SD lower. Compared to 2.5 years of age, EP children showed catch up in terms of weight by 0.37SD, height by 0.42SD and head circumference by 0.13SD. Systolic and diastolic BP were lower by 2.3mmHg and 2.4mmHg respectively in EP children but these differences were accounted for by differences in height and BMI. Maternal smoking in pregnancy was associated with lower BP, children born before 24 weeks had higher systolic and children given postnatal steroids higher diastolic pressures. Conclusions: Poor postnatal growth seen after birth and at in the third year persists into school age. Catch up growth reduces some of the early deficit but is least for head growth. Despite serious postnatal growth restriction blood pressure appears similar in both EP and term classmates

Prematurity and respiratory outcomes program (PROP): Study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States

Background With improved survival rates, short- and long-term respiratory complications of premature birth are increasing, adding significantly to financial and health burdens in the United States. In response, in May 2010, the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) funded a 5-year $18.5 million research initiative to ultimately improve strategies for managing the respiratory complications of preterm and low birth weight infants. Using a collaborative, multi-disciplinary structure, the resulting Prematurity and Respiratory Outcomes Program (PROP) seeks to understand factors that correlate with future risk for respiratory morbidity. Methods/Design The PROP is an observational prospective cohort study performed by a consortium of six clinical centers (incorporating tertiary neonatal intensive care units [NICU] at 13 sites) and a data-coordinating center working in collaboration with the NHLBI. Each clinical center contributes subjects to the study, enrolling infants with gestational ages 23 0/7 to 28 6/7 weeks with an anticipated target of 750 survivors at 36 weeks post-menstrual age. In addition, each center brings specific areas of scientific focus to the Program. The primary study hypothesis is that in survivors of extreme prematurity specific biologic, physiologic and clinical data predicts respiratory morbidity between discharge and 1 year corrected age. Analytic statistical methodology includes model-based and non-model-based analyses, descriptive analyses and generalized linear mixed models. Discussion PROP incorporates aspects of NICU care to develop objective biomarkers and outcome measures of respiratory morbidity in the <29 week gestation population beyond just the NICU hospitalization, thereby leading to novel understanding of the nature and natural history of neonatal lung disease and of potential mechanistic and therapeutic targets in at-risk subjects

A randomised controlled trial of oxygen therapy on growth and development of preterm infants

Background: Physiological studies have shown that many preterm infants and infants with chronic lung disease may suffer chronic hypoxaemia, which possibly leads to poor growth and development. Anecdotal reports indicate that there is a drive to increase the oxygen saturation target range to a higher level in these infants due primarily to perceived benefits derived from clinical experience and from uncontrolled observational studies of babies discharged on home oxygen. Objective The BOOST (Benefits Of Oxygen Saturation Targeting) trial is the first randomised trial to assess the long-term benefits and harms of two different oxygen saturation target ranges. Methods: BOOST was a multicentre, double blinded, randomised controlled trial that enrolled 358 infants born at less than 30 weeks� gestation who remained oxygen-dependent at 32 weeks postmenstrual age. They were randomly assigned to target either a functional oxygen saturation range of 91-94% (standard or control group) or 95-98% (higher or treatment group). The primary outcomes were growth and neurodevelopmental measures at 12 months corrected age. Secondary outcomes included length of hospital stay, retinopathy of prematurity, health service utilisation, parental stress, and infant temperament. Results: Prognostic baseline characteristics did not differ between the two groups. Mean birth weight and gestational age of enrolled infants was 917g and 26.5 weeks respectively. The rate of antenatal corticosteroid use was 83%

A randomised controlled trial of oxygen therapy on growth and development of preterm infants

Background: Physiological studies have shown that many preterm infants and infants with chronic lung disease may suffer chronic hypoxaemia, which possibly leads to poor growth and development. Anecdotal reports indicate that there is a drive to increase the oxygen saturation target range to a higher level in these infants due primarily to perceived benefits derived from clinical experience and from uncontrolled observational studies of babies discharged on home oxygen. Objective The BOOST (Benefits Of Oxygen Saturation Targeting) trial is the first randomised trial to assess the long-term benefits and harms of two different oxygen saturation target ranges. Methods: BOOST was a multicentre, double blinded, randomised controlled trial that enrolled 358 infants born at less than 30 weeks� gestation who remained oxygen-dependent at 32 weeks postmenstrual age. They were randomly assigned to target either a functional oxygen saturation range of 91-94% (standard or control group) or 95-98% (higher or treatment group). The primary outcomes were growth and neurodevelopmental measures at 12 months corrected age. Secondary outcomes included length of hospital stay, retinopathy of prematurity, health service utilisation, parental stress, and infant temperament. Results: Prognostic baseline characteristics did not differ between the two groups. Mean birth weight and gestational age of enrolled infants was 917g and 26.5 weeks respectively. The rate of antenatal corticosteroid use was 83%

Influence of Common Non-Synonymous Toll-like Receptor 4 Polymorphisms on Bronchopulmonary Dysplasia and Prematurity in Human Infants

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease and major risk factor for severe respiratory syncytial virus (RSV) infection among preterm infants. The Toll-like receptor 4 (TLR4) is involved in oxidative injury responses in the lungs. Two non-synonymous single nucleotide polymorphisms in the TLR4 gene have been associated with RSV infection in children. However, it is unclear to what extent this association is confounded by BPD or prematurity. In this study, we analyzed two population-based cohorts of preterm infants at risk for BPD as well as ethnicity-matched infants born at term, to test whether the TLR4 polymorphisms Asp299Gly (rs4986790) and Thr399Ile (rs4986791) are independently associated with BPD or premature birth. In a Canadian cohort (n = 269) composed of a majority of Caucasian preterm infants (BPD incidence of 38%), the TLR4-299 heterozygous genotype was significantly under-represented in infants without BPD (1.6% of infants versus 12% in infants with severe BPD) after adjusting for twins, ethnicity, gestational age, birth weight and gender (p = 0.014). This association was not replicated in a Finnish cohort (n = 434) of premature singletons or first-born siblings of Caucasian descent, although the incidence of BPD was substantially lower in this latter population (15%). We did not detect a significant association (>2-fold) between TLR4 genotypes and prematurity (p>0.05). We conclude that these TLR4 genotypes may have, at best, a modest influence on BPD severity in some populations of high-risk preterm infants. Further studies are warranted to clarify how clinical heterogeneity may impact genetic susceptibility to BPD

Outcomes and risk factors of very low birth weight infants with intraventricular haemorrhage who received respiratory support in a middle income country neonatal unit

Background: Prematurity is a major risk factor for intraventricular haemorrhage (IVH). Premature infants often require respiratory support. There is little information on neonates with IVH who require respiratory support in low and middle income countries. Objective: To describe the characteristics and short-term outcomes of very low birth weight (VLBW) infants with IVH who required respiratory support in a tertiary neonatal unit with resource limitations. Methods: This was a matched retrospective observational study. The population included VLBW infants with IVH, who received positive pressure respiratory support between January 2014 and December 2016. Outcomes of infants with severe IVH was compared to those with mild IVH. Outcomes were further analysed according to mode of ventilation. Results: 150 infants were included in the study, 56 (37%) received continuous positive airway pressure (CPAP) only and 94 (63%) mechanical ventilation. Severe IVH was associated with surfactant therapy across both ventilation groups (p=0.03). Oxygen requirement at 28 days was more frequent in infants with severe IVH compared to mild IVH (79% vs 38%, p=0.01) (OR 6.11 (95% CI 1.19-31.34), p=0.03). Severe IVH and the presence of coagulopathy were the strongest predictors of death in both ventilation groups (p <0.0001). Pulmonary haemorrhage was the commonest cause of death in those with severe IVH and blood culture confirmed sepsis in those with mild IVH. Periventricular leukomalacia (PVL) was associated with severe IVH in those receiving invasive ventilation (OR 6.67 (95% CI 1.11-40.17)). Conclusion: Mechanical ventilation, coagulopathy and pulmonary haemorrhage were strongly associated with death in VLBW infants with severe IVH in a resource-limited setting. These prognostic factors may have a role in end of life decisions