Familial and Genetic Susceptibility to Major Neonatal Morbidities in Preterm Twins

Bhandari, Vineet; Bizzarro, Matthew J.; Shetty, Anupama; Zhong, Xiaoyun; Page, Grier P.; Zhang, Heping; Ment, Laura R.; Gruen, Jeffrey R.

doi:10.1542/peds.2005-1414

Cited by 306 publications

(209 citation statements)

References 27 publications

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“…While changes in ventilation management could potentially impact in the 26 to 28 weeks GA category of infants, for the smallest group, especially with the advent of 'new' BPD, genetic approaches should be paramount. 38 With the current explosion of genomic techniques and decreasing cost, this is now a viable option.…”

Section: Characteristics Of Infants With Bpdmentioning

confidence: 99%

Site-specific characteristics of infants developing bronchopulmonary dysplasia

et al. 2006

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Hypothesis: Site-specific variables that contribute to the pathogenesis of bronchopulmonary dysplasia (BPD) can be identified.Objectives: To evaluate the demographic, nutrition and growth characteristics of infants at risk for developing BPD at two neonatal intensive care units (NICUs: sites A and O).Study Design: Records of 306 infants of <30 weeks gestational age (GA) who survived to at least 36 weeks postmenstrual age were retrospectively reviewed. Data were obtained for maternal and neonatal demographics, weights, total fluids, calories, carbohydrate, protein and fat intake at birth, 7, 14, 21 and 28 days of life.Results: BPD rates were not different at the two sites. No statistical differences were noted in the incidence of maternal chorioamnionitis, pregnancy-induced hypertension or use of antenatal steroids among infants who developed BPD (n ¼ 169) and those who did not (n ¼ 137). White race, birth weight, respiratory distress syndrome requiring surfactant, sepsis and patent ductus arteriosus were significantly associated (all Pp0.03) with BPD. After controlling for significant confounding variables, infants who developed BPD had significantly (P<0.001) less weight gain, received less calories and fat in the first postnatal month. In the 26 to 28 weeks GA group, the odds of getting BPD were 5.4 (95%CI: 1.4 to 21.3) times greater for site A than site O (P ¼ 0.017).Conclusion: Our analysis suggests that while some decrease in BPD can be achieved by focusing on ventilation/oxygen use, this approach is unlikely to impact on the youngest infants.

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Section: Characteristics Of Infants With Bpdmentioning

confidence: 99%

Site-specific characteristics of infants developing bronchopulmonary dysplasia

et al. 2006

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“…Environmental factors, such as high levels of oxygen exposure, mechanical ventilation, or repeated infections play a major role in etiology, although recent studies have suggested an important genetic predisposition. 1 Infants with BPD are at increased risk of death, childhood respiratory complications and long-term neurodevelopmental problems. 2,3 The lack of sustained clinical benefits from late postnatal therapeutic interventions and the undesirable harmful effects of post-natal corticosteroids have fueled interest in seeking early biological markers useful in targeting therapeutic interventions aimed at promoting long-term pulmonary and neurodevelopmental benefits.…”

Section: Introductionmentioning

confidence: 99%

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

2008

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Objective-The goal was to determine the magnitude of genetic effects on susceptibility and risk factors for bronchopulmonary dysplasia by using the clinically validated National Institutes of Health consensus definition as a demonstrated proxy for long-term respiratory and neurodevelopmental outcomes in extremely low birth weight infants.Methods-We analyzed clinical data from twin pairs born at ≤30 completed weeks gestation in British Columbia, Canada, between 1993 and 2006. Differences in correlations between monozygotic (MZ) and dizygotic (DZ) twin pairs and model-fitting approaches were used to quantify the relative contribution of genetic, shared environmental and non-shared environmental effects.Results-Among 318 twins of known zygosity, monozygotic twin pair similarities were greater than those observed for dizygotic pairs, which suggest significant heritability for bronchopulmonary dysplasia. Model-fitting analyses confirmed that genetic effects accounted for 82% and 79% of the observed variance in bronchopulmonary dysplasia susceptibility, defined on the basis of the need for supplemental oxygen at 36 weeks or the National Institutes of Health consensus definition, respectively. Variations in rates of hemodynamically significant PDA were largely accounted for by genetic effects, whereas variance in susceptibility to blood-borne bacterial infections was largely attributable environmental factors both common and unique to each infant.Conclusions-Susceptibility to BPD and persistence of PDA are both significantly heritable. Our study strengthens the case for investigating further genetic risk stratification markers useful for predicting the most significant long-term respiratory and neurodevelopmental consequences of bronchopulmonary dysplasia in premature neonates.

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“…2,5,6 Sepsis in utero, in addition to ventilator-induced injury and hyperoxia, initiates an inflammatory cascade, which acts on the immature lungs. 2 Inflammation interferes with the normal development of airways and alveoli, and abnormal healing in the premature infant further exacerbates lung damage, resulting in BPD.…”

Section: Introductionmentioning

confidence: 99%

Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone

et al. 2007

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Objectives: To study the association between angiopoietin 2 (Ang2) concentrations in tracheal aspirates (TAs) and adverse outcome (bronchopulmonary dysplasia (BPD)/death) in ventilated premature infants (VPIs) and modulation of Ang2 concentrations with dexamethasone (Dex) use.Study Design: Serial TA samples were collected on days 1, 3, 5 and 7, and Ang2 concentrations were measured. Ang2 TA concentrations were compared prior to and after 48 to 72 h of using Dex.Result: A total of 151 TA samples were collected from 60 VPIs. BPD was defined as the oxygen requirement at 36 weeks postmenstrual age (PMA). Twelve infants (mean ± s.d.) (gestational age (GA) 26.5 ± 2.1 weeks, birth weight (BW) 913±230 g) had no BPD, 32 infants (GA 25.8±1.4 weeks, BW 768 ± 157 g) developed BPD and 16 infants (GA 24.5 ± 1.1 weeks, BW 710 ± 143 g) died before 36 weeks PMA. Ang2 concentrations were significantly lower in infants with no BPD (median, 25th and 75th percentile) (157, 16 and 218 pg mg À1 ) compared with those who developed BPD (234, 138 and 338 pg mg À1 , P ¼ 0.03) or BPD and/or death (234, 157 and 347 pg mg À1 , P ¼ 0.017), in the first week of life. Twenty-six VPIs (BW 719±136 g, GA 25.1±1.3 weeks) received 27 courses of Dex. Ang2 concentrations before starting Dex were 202, 137 and 278 pg mg À1 and significantly decreased to 144, 0 and 224 pg mg À1 after therapy (P ¼ 0.007).Conclusions: Higher Ang2 concentrations in TAs are associated with the development of BPD or death in VPIs. Dex use suppressed Ang2 concentrations.

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Familial and Genetic Susceptibility to Major Neonatal Morbidities in Preterm Twins

Abstract: Twin analyses show that intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia are familial in origin. These data demonstrate, for the first time, the significant genetic susceptibility for bronchopulmonary dysplasia in preterm infants.

Cited by 306 publications

References 27 publications

Site-specific characteristics of infants developing bronchopulmonary dysplasia

Site-specific characteristics of infants developing bronchopulmonary dysplasia

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone

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