Survivors Of Prematurity Research Articles

Long-term Follow Up of Patients Treated with D-Penicillamine in the Neonatal Period

Background: In neonatal therapy D-penicillamine (D-PA) was first recognized to have a potential benefit for neonatal hyperbilirubinemia in the early 1970s. Controlled, randomized clinical trials confirmed the effectiveness of D-PA in the treatment of haemolytic disease of the newborn and retinopathy of prematurity. The aim of this study was to explore potential long-term effects of D-PA by measuring health state of adults treated with this drug in the newborn period. Methods: The self-perceived health and health related quality of life (HRQoL) have been investigated in a cohort of 23-36 years old patients using the EuroQol5D instrument. Self-administered questionnaires were mailed comprising EQ-5D instrument and questions on academic achievements, and presence of neurosensory impairments. The original cohort consisted of 1492 subjects. 518 participants returned the questionnaires, of which 32 had to be excluded due to incomplete responses. As reference, the data of the quality of life survey was used; this study was conducted in the early years of 2000, on a representative sample of 5503 members of a Hungarian population with average achievement [22]. Results: The occurrence of neurosensory disabilities and educational levels on HRQoL were also evaluated. The authors have examined the bias between those who returned complete questionnaires and those who returned incomplete questionnaires. In all age groups of the cohort the mean Visual Analogue Scale (VAS) score was remarkable higher, whereas the mean EQ-5D index was lower than the Hungarian age specific value, which discordance can be explained by the disability paradox. Significantly more respondents with VLBW compared to their term peers reported to have neurosensory impairment and lower educational level. Conclusions: The different characteristics of incomplete respondents can lead to large biases and through that way have great influence on HRQoL estimates. Focusing on the potential effects of D-PA, the following facts are verifiable: (i) adults survivors of prematurity can suffer from numerous pathological conditions. Consequently, their health/behaviors were significantly weaker (as it was expected) in comparison with the average population's examined [22] (ii) on the other hand, those adults who were born at term, their health/behaviors were better. This was, however, statistically not significant.

Adults born preterm exhibit bi‐ventricular hypercontractility and inefficiency

IntroductionIn the US, prematurity accounts for approximately 10% of all live births. Infants born preterm are at an increased risk of cardiopulmonary disease. Until recently, little was known about the long‐term sequelae in the myocardium in adult survivors of prematurity. One study demonstrated that adults born preterm had larger left (LV) and right ventricular (RV) masses, and lower RV ejection fraction compared to term born controls. To date, there is a paucity of information on the potential mechanism of altered ventricular mechanics in adult survivors of prematurity. Therefore, we hypothesized that preterm subjects would display reduced RV and LV strain.MethodsPreterm subjects were recruited from a prospectively followed cohort at UW‐Madison. Gestational ages for the preterm subjects were 28.2 ± 0.84 weeks and they weighed < 1500 grams. Term‐born subjects were recruited from the general public. Cardiac magnetic resonance imaging (MRI) was used to determine myocardial strain and stroke volume (SV) in adults born preterm (n = 10, age = 26.9 ± 0.3 years) and age‐matched term born controls (n = 12, age = 25.8 ± 0.2 years). Three slices from the RV and LV (apex, mid and base) short‐axis cine MR images were used to analyze RV and LV circumferential and LV radial dimensions (mean peak strain, systolic and diastolic strain rate). SV was obtained from the main pulmonary artery (MPA) and aorta (Ao) 2‐D phase contrast images. SV was normalized to body surface area (SVI) and was divided by peak RV and LV circumferential strain to obtain RV and LV efficiency. All MRI analysis was performed using Segment (http://segment.heiberg.se). A Mann‐Whitney test was performed to test differences between groups (p < 0.05).ResultsPreterm subjects demonstrated increased peak RV circumferential (−11.36 % ± 1.90 vs. −8.83 % ± 1.95; p = 0.003) and LV circumferential (−20.15 % ± 2.29 vs. −17.96 % ± 1.96; p = 0.025) strain compared to controls, respectively. Additionally, RV circumferential systolic strain rate, LV circumferential systolic and diastolic strain rate, and LV radial diastolic strain rate were greater (p < 0.05) in preterm adults as compared to controls. SVI as measured from the MPA and Ao flow was not different between groups. Preterm subjects exhibited reduced (p < 0.05) RV and LV (p = 0.06) efficiency as compared to controls.DiscussionWe used MRI to measure RV and LV strain, which is a measure of ventricular displacement during the cardiac cycle. Contrary to our hypothesis, these results demonstrate that adults born preterm exhibit a hypercontractile myocardium (increased strain) under resting conditions. The increased bi‐ventricular strain in the circumferential dimension in preterm born adults occurred despite no differences in SVI between groups. This results in reduced RV and LV efficiency in preterm subjects compared to controls, suggesting increased cardiac work may be required in adults born preterm for the same SVI. The implications for life‐time cardiovascular risk merit further study.Support or Funding InformationProject supported by funding from the National Institutes of Health: 1RO1 HL086897 (MWE) and RO1 HL38149 (MWE). Kara Goss is supported by the University of Wisconsin Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant NIH UL1TR000427 (PI Drezner; 4KL2TR000428‐‐10).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of extremely low-birth-weight status on risk and resilience for depression and anxiety in adulthood.

Preterm birth is associated with an increased risk of depression and anxiety, but it is not known if this is due to greater exposure to risk, or if perinatal adversity amplifies the impact of traditional risk factors. This study sought to determine if exposure to perinatal adversity modifies associations between traditional risk and resilience factors and depression and anxiety in adulthood. A sample of 142 extremely low-birth-weight (ELBW<1,000g) survivors and 133 sociodemographically matched normal birth weight (NBW) control participants was followed longitudinally to 22-26years of age. Separate postnatal risk and resilience scales were created using eight risk and seven resilience factors, respectively. Depression and anxiety were assessed using the internalizing scale of the Young Adult Self-Report (YASR). This scale was also dichotomized at the 90th percentile to define clinically significant psychopathology. While the average number of risk exposures did not differ between groups, ELBW survivors were more susceptible to risk than NBW control participants. For the ELBW group, each additional risk factor resulted in a 2-point increase in internalizing scores, and two and a half times the odds of clinically significant internalizing symptoms (OR=2.47, 95% CI=1.63, 3.76). The protective effect of resiliency factors was also blunted among ELBW survivors. Extremely low-birth-weight survivors may be more sensitive to traditional risk factors for psychopathology and less protected by resiliency factors. Intervention strategies aimed at preventing or reducing exposure to traditional childhood risk factors for psychopathology may reduce the burden of mental illness in adult survivors of prematurity.

INFECTIONS AND PREMATURITY, IMPORTANT RISK FACTORS FOR NEONATAL MORBIDITY AND MORTALITY

Infant mortality is a major problem in developing countries and, unfortunately, this is the case of our country as well, given that Romania ranks first in the European Union in this respect, with an infant mortality rate of 9 ‰, compared to an average of roughly 4 ‰. Worldwide, over 15 million babies are born prematurely each year and, out of these, more than a million die due to prematurity and infections, which are the main risk factors for neonatal mortality. The risk of infection is several times higher in preterm newborns than in full-term newborns – about 80% of neonatal infections occur in premature infants. A significant proportion of the survivors of prematurity will have important neurological sequelae because of neonatal infections as well as of intracerebral bleeding or hypoxia at birth. Continuing medical education in both the general population and the medical sector is crucial in preventing premature births and neonatal infections and, consequently, in decreasing infant morbidity and mortality rates in our country.

THE SURVIVAL OF PREMATURE INFANTS DEPENDING ON THE LEVEL OF MEDICAL ASSISTANCE

Worldwide, premature birth is the main cause of infant mortality and a significant cause of human potential loss of premature survivors for the next stages of life. Purpose. To determine the rate of premature infants survival depending on the level of medical assistance and the main risk factors involved in the death of preterm infants with gestational age less than 34 weeks. Materials and methods. We included in the study 750 preterm newborns divided into three groups as follows: group 1 – 476 premature newborns born in IMSP IMsC, Chisinau (level III maternity); group 2 – 240 premature infants transferred by the AVIASAN service from level I and II maternities to the level III unit and group 3 – 34 premature babies from IMSP IMsC Chisinau that received surfactant administered by the LISA method (Less Invasive Surfactant Administration). We performed a complex analysis of the risk factors for death and the positive impact of highly specialised care on survival. The data was analysed using SPSS V.21 software (IBM Statistical Package for the Social Sciences, Chicago, Illinois). Results. The survival rate at 78 days of life was significantly higher in the newborns from the level III maternity that received LISA therapy (93.3%), compared to those in group 1 (78.2%) and group 2 (78.9%) respectively. Conclusions. The survival of premature infants is a multifactorial problem. The main factor that determines the rate of death for these infants is respiratory distress syndrome (RDS), followed by birth weight (BW), gestational age (GA), resuscitation method, bronchopulmonary dysplasia (BPD) and last but not least by the level of maternity where the infants were born. These factors might be considered predictive for death of preterm newborns with gestational age less than 34 weeks.

Cognitive, Mental Health, and Adaptive Outcomes Among Survivors of Prematurity

Children born prematurely often experience significant medical issues early in life. Though some of these individuals continue to experience ongoing challenges throughout their lives as a result of prematurity, others are less affected. This article reviews the current data about cognitive, mental health, and adaptive outcomes among survivors of prematurity, to inform and empower clinicians to effectively counsel and support those affected by prematurity.

Cerebral Palsy, Developmental Coordination Disorder, Visual and Hearing Impairments in Infants Born Preterm

Motor disabilities and neurosensory impairments are common in survivors of prematurity, and significantly affect quality of life. Cerebral palsy occurs with a much higher prevalence in preterm survivors compared with term infants; however, another less severe but important neuromotor condition is developmental coordination disorder. Visual and hearing impairments are less common, but significantly compound physical disabilities. Early identification and referral for services are important to optimize functioning, learning, and community supports for these children. This article provides a review of prevalence, at-risk factors, presenting signs and symptoms, and management strategies for these conditions.

A population study of respiratory rehospitalisation in very preterm infants in the first 3 years of life.

Very premature infants consume healthcare resources following discharge from neonatal intensive care units (NICU). This study aimed to evaluate the burden of respiratory related rehospitalisation within the first 3 years post discharge in very premature infants in an Australian population. Rehospitalisation of a 4-year cohort of NICU survivors, born less than 32 weeks gestation, was derived from data linkage of three state-wide databases including NSW Neonatal Intensive Care Units' Data Collection, Admitted Patient Data Collection and the Death Registry. Rehospitalisation diagnoses were determined by ICD-10 AM codes. Of the 2939 survivors, 525 (18%) had bronchopulmonary dysplasia (BPD) and 261 BPD infants (50%) were discharged on home oxygen. Almost two-third (1860, 63%) of the survivors are required rehospitalisation, respiratory causes, including 394 respiratory syncytial virus (RSV)-related, accounted for 2668 (48%) of the 5599 rehospitalisations. Significantly more home oxygen BPD survivors had respiratory (70%) and RSV-related (22%) rehospitalisations than the BPD infants not needing home oxygen (58% and 18%, respectively), and the survivors without BPD had the lowest rates (32% and 10%, P < 0.001). Most respiratory (61%) and RSV-related (74%) rehospitalisations occurred during the first 12 months post discharge. No RSV-related fatality occurred. Amongst the total 17 562 hospital days, respiratory and RSV-related admissions accounted for 10 905 (62%) and 3031 (17.2%) days. In multivariable logistic analyses, home oxygen and maternal indigenous status were independently associated with high (3 or more) respiratory and RSV rehospitalisation rates. Respiratory rehospitalisations are common in very premature survivors. Home oxygen and indigenous status are significant risk factors for respiratory and RSV-related rehospitalisations.

Quality versus quantity: The complexities of quality of life determinations for neonatal nurses.

The ability to save the life of an extremely premature baby has increased substantially over the last decade. This survival, however, can be associated with unfavourable outcomes for both baby and family. Questions are now being asked about quality of life for survivors of extreme prematurity. Quality of life is rightly deemed to be an important consideration in high technology neonatal care; yet, it is notoriously difficult to determine or predict. How does one define and operationalise what is considered to be in the best interest of a surviving extremely premature baby, especially when the full extent of the outcomes might not be known for several years? The research investigates the caregiving dilemmas often faced by neonatal nurses when caring for extremely premature babies. This article explores the issues arising for neonatal nurses when they considered the philosophical and ethical questions about quality of life in babies ≤24 weeks gestation. Data were collected via a questionnaire to Australian neonatal nurses and semi-structured interviews with 24 neonatal nurses in New South Wales, Australia. Ethical considerations: Ethical processes and procedures have been adhered to by the researchers. A qualitative approach was used to analyse the data. The theme 'difficult choices' was generated which comprised three sub-themes: 'damaged through survival', 'the importance of the brain' and 'families are important'. The results show that neonatal nurses believed that quality of life was an important consideration; yet they experienced significant inner conflict and uncertainty when asked to define or suggest specific elements of quality of life, or to suggest how it might be determined. It was even more difficult for the nurses to say when an extremely premature baby's life possessed quality. Their previous clinical and personal experiences led the nurses to believe that the quality of the family's life was important, and possibly more so than the quality of life of the surviving baby. This finding contrasts markedly with much of the existing literature in this field. Quality of life for extremely premature babies was an important consideration for neonatal nurses; however, they experienced difficulty deciding how to operationalise such considerations in their everyday clinical practice.

PO-0441 Oxygen Reduction Initiative That Decreased Incidence And Severity Of Retinopathy Of Prematurity Results In Favourable Neuropsychological Outcomes At Age Three

Background and aims High oxygen exposure has adverse long-term medical consequences in premature infants. We hypothesised that a quality improvement initiative decreasing oxygen saturation limits in NICU-admitted infants would affect neuropsychological outcomes at age 3. Methods We studied 83 NICU-admitted participants born at 23–27 weeks; n = 37 (b.2009–2010) with targeted supplemental oxygen rates of 83–93% until 32 weeks, 85–95% until 35 weeks, and >95% after 35 weeks (O 2 Reduced); 8% laser eye surgery; 65% ROP compared with n = 46 (b.2007–2008) with higher target rates (89–100%; O 2 Higher); 28% laser eye surgery; 83% ROP. Group mortality rates ( 2 (n = 83, df=1)= 0.16, p = 0.900. ANCOVAs and regressions were conducted for 19 neuropsychological outcomes. Results O 2 Reduced performed significantly better than O 2 Higher in visual attention, controlling GA (p = 0.042; d= .47); O 2 Reduced was significantly correlated with visual attention (r = 0.288, p 5); ROP was not (r=-0.183, p > 0.05). 18/19 outcome scores favoured O 2 Reduced, low-to-moderate effect sizes ( d range:12–0.47). GA was positively related to all outcomes. A meaningful interaction effect between GA and O 2 Reduced for auditory attention and manual dexterity explained 3%-4% unique variance, respectively. Interaction showed O 2 Reduced’s effect on attention was greatest at 23–24 weeks, and at 27 weeks for manual dexterity. Conclusions Systematic reduction of saturation parameters that decreased retinopathy and laser surgery rates in infancy resulted in favourable three-year-old outcomes suggesting cognitive as well as medical advantages for O 2 Reduced. Moderate effect sizes demonstrated important associations between reduced oxygen saturation rates and 18/19 sensitive performance-based measures. Lowered targeted oxygen saturation rate had favourable yet differential effects across GA in extremely premature survivors.

A42 METABOLOMICS IN BRONCHOPULMONARY DYSPLASIA: PRELIMINARY RESULTS

Bronchopulmonary dysplasia (BPD) continues to represent a significant cause of morbidity among survivors of severe prematurity in the NICU. The increasing prevalence of BPD over the decades has been suggested to be related to the increased survival of extremely low birthweight infants.To evaluate differences in prevalence of BPD (BPD28d and BPD36wk) and as a function of survival rate in extremely low birth weight (ELBW) infants over time, and to explore its relationship with known associated risk factors.Survival rate and prevalence of oxygen-dependency =28 days (BPD28d) and oxygen-dependency =36 weeks postmenstrual age (BPD36wk) were evaluated in ELBW newborns (mean gestational age: 27.12.2 weeks; mean birth weight: 817142 g) consecutively admitted to the Brindisi NICU over the last 26 years. Two arbitrarily chosen time periods were compared: Period 1: July 1st, 1986 to June 30, 2002 vs. Period 2: July 1st, 2002 to December 31, 2012. Analyzed variables included gestational age, birth weight, intubation time, hours of O2 administration, NCPAP, and use of surfactant. Differences between the time periods were assessed by chi-square statistics, Fisher's tests or Mann–Whitney test, as appropriate. A two-tailed p value <0.05 was considered to indicate statistical significance.Survival rate of ELBW infants over the examined time periods dramatically improved from 42.3% to 72.6% (p < 0.0001), whereas changes in the prevalence of BPD28d and BPD36wk were not statistically significant (30.5% vs. 39.3%, p = 0.2137 and 5.5% vs. 13.1%, p = 0.1452, respectively). Likewise, BPD severity was not significantly different between the two time periods (p = 0.1635). Gestational age and birth weight of surviving neonates did not significantly change between the two time periods (p = 0.8050 and p = 0.6986, respectively), whereas significantly increased intubation time (median values: 144 hours vs. 33 hours, p <0.0001) and use of exogenous surfactant (89.3% vs. 48.6%, p < 0.0001) was evidenced for the second time period, as well as NCPAP (median values: 600 hours vs. 377 hours, p = 0.0005). A statistically non-significant trend for a prolonged O2 administration in period 2 (p = 0.0850) was also observed.Our findings indicate that a significantly increased survival is not necessarily associated with a significant difference in the prevalence of BPD among ELBW infants.

Survival rate and prevalence of bronchopulmonary dysplasia in extremely low birth weight infants

Bronchopulmonary dysplasia (BPD) continues to represent a significant cause of morbidity among survivors of severe prematurity in the NICU. The increasing prevalence of BPD over the decades has been suggested to be related to the increased survival of extremely low birthweight infants. To evaluate differences in prevalence of BPD (BPD28d and BPD36wk) and as a function of survival rate in extremely low birth weight (ELBW) infants over time, and to explore its relationship with known associated risk factors. Survival rate and prevalence of oxygen-dependency =28 days (BPD28d) and oxygen-dependency =36 weeks postmenstrual age (BPD36wk) were evaluated in ELBW newborns (mean gestational age: 27.12.2 weeks; mean birth weight: 817142 g) consecutively admitted to the Brindisi NICU over the last 26 years. Two arbitrarily chosen time periods were compared: Period 1: July 1st, 1986 to June 30, 2002 vs. Period 2: July 1st, 2002 to December 31, 2012. Analyzed variables included gestational age, birth weight, intubation time, hours of O2 administration, NCPAP, and use of surfactant. Differences between the time periods were assessed by chi-square statistics, Fisher's tests or Mann-Whitney test, as appropriate. A two-tailed p value <0.05 was considered to indicate statistical significance. Survival rate of ELBW infants over the examined time periods dramatically improved from 42.3% to 72.6% (p < 0.0001), whereas changes in the prevalence of BPD28d and BPD36wk were not statistically significant (30.5% vs. 39.3%, p = 0.2137 and 5.5% vs. 13.1%, p = 0.1452, respectively). Likewise, BPD severity was not significantly different between the two time periods (p = 0.1635). Gestational age and birth weight of surviving neonates did not significantly change between the two time periods (p = 0.8050 and p = 0.6986, respectively), whereas significantly increased intubation time (median values: 144 hours vs. 33 hours, p <0.0001) and use of exogenous surfactant (89.3% vs. 48.6%, p < 0.0001) was evidenced for the second time period, as well as NCPAP (median values: 600 hours vs. 377 hours, p = 0.0005). A statistically non-significant trend for a prolonged O2 administration in period 2 (p = 0.0850) was also observed. Our findings indicate that a significantly increased survival is not necessarily associated with a significant difference in the prevalence of BPD among ELBW infants.

A40 VALPROIC ACID-MEDIATED PROTECTION AGAINST HYPEROXIC LUNG INJURY VIA HISTONE DEACETYLASE INHIBITION IN A NEONATAL RAT MODEL

Bronchopulmonary dysplasia (BPD) continues to represent a significant cause of morbidity among survivors of severe prematurity in the NICU. The increasing prevalence of BPD over the decades has been suggested to be related to the increased survival of extremely low birthweight infants.To evaluate differences in prevalence of BPD (BPD28d and BPD36wk) and as a function of survival rate in extremely low birth weight (ELBW) infants over time, and to explore its relationship with known associated risk factors.Survival rate and prevalence of oxygen-dependency =28 days (BPD28d) and oxygen-dependency =36 weeks postmenstrual age (BPD36wk) were evaluated in ELBW newborns (mean gestational age: 27.12.2 weeks; mean birth weight: 817142 g) consecutively admitted to the Brindisi NICU over the last 26 years. Two arbitrarily chosen time periods were compared: Period 1: July 1st, 1986 to June 30, 2002 vs. Period 2: July 1st, 2002 to December 31, 2012. Analyzed variables included gestational age, birth weight, intubation time, hours of O2 administration, NCPAP, and use of surfactant. Differences between the time periods were assessed by chi-square statistics, Fisher's tests or Mann–Whitney test, as appropriate. A two-tailed p value <0.05 was considered to indicate statistical significance.Survival rate of ELBW infants over the examined time periods dramatically improved from 42.3% to 72.6% (p < 0.0001), whereas changes in the prevalence of BPD28d and BPD36wk were not statistically significant (30.5% vs. 39.3%, p = 0.2137 and 5.5% vs. 13.1%, p = 0.1452, respectively). Likewise, BPD severity was not significantly different between the two time periods (p = 0.1635). Gestational age and birth weight of surviving neonates did not significantly change between the two time periods (p = 0.8050 and p = 0.6986, respectively), whereas significantly increased intubation time (median values: 144 hours vs. 33 hours, p <0.0001) and use of exogenous surfactant (89.3% vs. 48.6%, p < 0.0001) was evidenced for the second time period, as well as NCPAP (median values: 600 hours vs. 377 hours, p = 0.0005). A statistically non-significant trend for a prolonged O2 administration in period 2 (p = 0.0850) was also observed.Our findings indicate that a significantly increased survival is not necessarily associated with a significant difference in the prevalence of BPD among ELBW infants.

A15 SNIPPING NEONATAL TONGUE-TIES: WITH OR WITHOUT ANESTHESIA?

Bronchopulmonary dysplasia (BPD) continues to represent a significant cause of morbidity among survivors of severe prematurity in the NICU. The increasing prevalence of BPD over the decades has been suggested to be related to the increased survival of extremely low birthweight infants.To evaluate differences in prevalence of BPD (BPD28d and BPD36wk) and as a function of survival rate in extremely low birth weight (ELBW) infants over time, and to explore its relationship with known associated risk factors.Survival rate and prevalence of oxygen-dependency =28 days (BPD28d) and oxygen-dependency =36 weeks postmenstrual age (BPD36wk) were evaluated in ELBW newborns (mean gestational age: 27.12.2 weeks; mean birth weight: 817142 g) consecutively admitted to the Brindisi NICU over the last 26 years. Two arbitrarily chosen time periods were compared: Period 1: July 1st, 1986 to June 30, 2002 vs. Period 2: July 1st, 2002 to December 31, 2012. Analyzed variables included gestational age, birth weight, intubation time, hours of O2 administration, NCPAP, and use of surfactant. Differences between the time periods were assessed by chi-square statistics, Fisher's tests or Mann–Whitney test, as appropriate. A two-tailed p value <0.05 was considered to indicate statistical significance.Survival rate of ELBW infants over the examined time periods dramatically improved from 42.3% to 72.6% (p < 0.0001), whereas changes in the prevalence of BPD28d and BPD36wk were not statistically significant (30.5% vs. 39.3%, p = 0.2137 and 5.5% vs. 13.1%, p = 0.1452, respectively). Likewise, BPD severity was not significantly different between the two time periods (p = 0.1635). Gestational age and birth weight of surviving neonates did not significantly change between the two time periods (p = 0.8050 and p = 0.6986, respectively), whereas significantly increased intubation time (median values: 144 hours vs. 33 hours, p <0.0001) and use of exogenous surfactant (89.3% vs. 48.6%, p < 0.0001) was evidenced for the second time period, as well as NCPAP (median values: 600 hours vs. 377 hours, p = 0.0005). A statistically non-significant trend for a prolonged O2 administration in period 2 (p = 0.0850) was also observed.Our findings indicate that a significantly increased survival is not necessarily associated with a significant difference in the prevalence of BPD among ELBW infants.

A26 GRAM-NEGATIVE INFECTIONS IN UK NEONATAL UNITS – CASE HISTORY AND EXPERT OPINION

Bronchopulmonary dysplasia (BPD) continues to represent a significant cause of morbidity among survivors of severe prematurity in the NICU. The increasing prevalence of BPD over the decades has been suggested to be related to the increased survival of extremely low birthweight infants.To evaluate differences in prevalence of BPD (BPD28d and BPD36wk) and as a function of survival rate in extremely low birth weight (ELBW) infants over time, and to explore its relationship with known associated risk factors.Survival rate and prevalence of oxygen-dependency =28 days (BPD28d) and oxygen-dependency =36 weeks postmenstrual age (BPD36wk) were evaluated in ELBW newborns (mean gestational age: 27.12.2 weeks; mean birth weight: 817142 g) consecutively admitted to the Brindisi NICU over the last 26 years. Two arbitrarily chosen time periods were compared: Period 1: July 1st, 1986 to June 30, 2002 vs. Period 2: July 1st, 2002 to December 31, 2012. Analyzed variables included gestational age, birth weight, intubation time, hours of O2 administration, NCPAP, and use of surfactant. Differences between the time periods were assessed by chi-square statistics, Fisher's tests or Mann–Whitney test, as appropriate. A two-tailed p value <0.05 was considered to indicate statistical significance.Survival rate of ELBW infants over the examined time periods dramatically improved from 42.3% to 72.6% (p < 0.0001), whereas changes in the prevalence of BPD28d and BPD36wk were not statistically significant (30.5% vs. 39.3%, p = 0.2137 and 5.5% vs. 13.1%, p = 0.1452, respectively). Likewise, BPD severity was not significantly different between the two time periods (p = 0.1635). Gestational age and birth weight of surviving neonates did not significantly change between the two time periods (p = 0.8050 and p = 0.6986, respectively), whereas significantly increased intubation time (median values: 144 hours vs. 33 hours, p <0.0001) and use of exogenous surfactant (89.3% vs. 48.6%, p < 0.0001) was evidenced for the second time period, as well as NCPAP (median values: 600 hours vs. 377 hours, p = 0.0005). A statistically non-significant trend for a prolonged O2 administration in period 2 (p = 0.0850) was also observed.Our findings indicate that a significantly increased survival is not necessarily associated with a significant difference in the prevalence of BPD among ELBW infants.

Catch-up alveolarization in ex-preterm children: evidence from (3)He magnetic resonance.

Histologic data from fatal cases suggest that extreme prematurity results in persisting alveolar damage. However, there is new evidence that human alveolarization might continue throughout childhood and could contribute to alveolar repair. To examine whether alveolar damage in extreme-preterm survivors persists into late childhood, we compared alveolar dimensions between schoolchildren born term and preterm, using hyperpolarized helium-3 magnetic resonance. We recruited schoolchildren aged 10-14 years stratified by gestational age at birth (weeks) to four groups: (1) term-born (37-42 wk; n = 61); (2) mild preterm (32-36 wk; n = 21); (3) extreme preterm (<32 wk, not oxygen dependent at 4 wk; n = 19); and (4) extreme preterm with chronic lung disease (<32 wk and oxygen dependent beyond 4 wk; n = 18). We measured lung function using spirometry and plethysmography. Apparent diffusion coefficient, a surrogate for average alveolar dimensions, was measured by helium-3 magnetic resonance. The two extreme preterm groups had a lower FEV1 (P = 0.017) compared with term-born and mild preterm children. Apparent diffusion coefficient was 0.092 cm(2)/second (95% confidence interval, 0.089-0.095) in the term group. Corresponding values were 0.096 (0.091-0.101), 0.090 (0085-0.095), and 0.089 (0.083-0.094) in the mild preterm and two extreme preterm groups, respectively, implying comparable alveolar dimensions across all groups. Results did not change after controlling for anthropometric variables and potential confounders. Alveolar size at school age was similar in survivors of extreme prematurity and term-born children. Because extreme preterm birth is associated with deranged alveolar structure in infancy, the most likely explanation for our finding is catch-up alveolarization.

173 Clues for the Neurodevelopmental Prognosis of the High Risk Preterm and Term Newborns

Premature survivors are at increased risk for impaired neurodevelopmental outcome compared to full terms. These sequelae include cognitive abnormalities, mild fine or gross motor delay, cerebral palsy, vision and hearing...

Mechanisms of Perinatal Brain Injury

The guest editors of this journal are pleased to introduce this special issue on the mechanisms of perinatal brain injury. The purpose of this issue is to highlight recent developments toward our understanding of both grey and white matter injury in the perinatal brain. Over the last decade, there has been significant advancement in our understanding of the mechanisms underlying this injury. The progression of the field stems from many factors including: (1) the development and refinement of experimental models; (2) advances in modern imaging technologies, such as magnetic resonance imaging and diffusion tensor imaging; (3) detailed characterization of the injury, both in human and animals, on the anatomical, cellular, and subcellular levels and (4) identification of the developmental factors that underlie the vulnerability of the perinatal brain to such injury. Here we present nine review and two research articles that together highlight these advancements, as summarized below. It has been our honor to work with each of the contributing scientists, and we thank them for their commitment to this Special Issue. The review by C. Thornton et al. summarizes our current understanding of the “Molecular mechanisms of perinatal brain injury,” with a focus on mitochondrial functional impairment and apoptotic events during the secondary injury phase. The authors also present the most up-to-date intervention strategies targeting the different stages of brain injury. V. Ten and A. Starkov further explore the role of mitochondria in hypoxic-ischemic (H-I) injury and provide evidence for the mitochondrial production of reactive oxygen species as a pathogenic mechanism underlying this injury. The authors summarize experimental data delineating mitochondrial sources of reactive oxygen species and their specific targets in neonatal animals. Necrotic cell death is well documented in H-I brain injury and is traditionally thought uncontrollable. In another review, R. Chavez-Valdez et al. introduce the recently identified RIP1/3 kinase dependent programmed necrosis pathway to the field of neonatal brain injury and propose an apoptosis-necrosis cell death “continuum” for cellular degeneration. The authors highlight experimental evidence supporting a prominent role of programmed necrosis in neonatal H-I brain injury. Another paper by C. Hill and R. Fitch explores the underlying basis of the increased vulnerability of male infants to H-I injury and their increased incidence of cognitive deficits associated with that injury. The authors discuss hormonal factors underlying these differences as well as sex-specific differences in H-I-induced cell death pathways. In the review by K. Buller et al., the effects of perinatal H-I injury on the serotonergic system are summarized. The potential use of anti-inflammatory interventions to alleviate this injury is also discussed. Disruption of this neurotransmitter system may underlie the cardiorespiratory, cognitive, and attention deficits observed in survivors of prematurity. Changing the focus from H-I injury to inflammation and infection, C. Mallard and X. Wang summarize clinical and experimental evidence for neonatal sepsis and increased vulnerability of the immature brain and discuss the involvement of Toll-like receptors (TLRs) in perinatal brain injury. Continuing in the area of inflammation and infection, R. McAdams and S. Juul address the initiation and activation of cytokines and inflammatory cells in the perinatal brain and their detrimental short and long-term consequences. They highlight the importance of understanding the dynamic structure of the blood brain barrier, as well as the relatively unknown mechanisms that impair its integrity allowing immune cells direct access to the brain. In the first of two research articles, D. Selip et al. characterize, in a rodent model of H-I, the spectrum of grey matter damage in association with the white matter damage once thought to be dominant in H-I injury. The authors characterize the regional susceptibility to H-I injury in terms of the inflammatory response, white matter injury and myelin loss, neuronal degeneration, and axonal injury. Our second research article by K. Shrivastava et al. provides an extensive characterization of the glia/inflammatory response following H-I using a common model of injury thought to spare the contralateral hemisphere. This study extends our knowledge of this model by characterizing a subtle inflammatory response in the contralateral brain, and provides important information regarding the timing of the insult in relationship to the initiation of inflammatory signaling cascades. The paper by V. Biran et al. highlights a novel area of the brain—the cerebellum—that has emerged as an important attribute of perinatal brain injury through imaging studies. This review provides an extensive detailed analysis of cerebellar development, and the implications of disrupting its normal maturation as a consequence of perinatal brain injury. Finally H. Kinney and J. Volpe stress the importance of developing and using animal models with a careful consideration of human perinatal brain development and injury. This paper emphasizes the need to model perinatal brain injury as an encephalopathy of prematurity characterized by a combination of both grey and white matter lesions.

Regulation of corticoid and serotonin receptor brain system following early life exposure of glucocorticoids: Long term implications for the neurobiology of mood

Potent glucocorticoids (GC) administered early in life have improved premature infant survival dramatically. However, these agents may increase the risk for physical, neurological and behavior alterations. Anxiety, depression and attention difficulties are commonly described in adolescent and young adult survivors of prematurity. In the present study we administered vehicle, dexamethasone, or hydrocortisone to Sprague-Dawley rat pups on postnatal days 5 and 6, mimicking a short term clinical protocol commonly used in human infants. Two systems that are implicated in the regulation of stress and behavior were assessed: the limbic-hypothalamic-pituitary-adrenal axis [LHPA; glucocorticoid and mineralocorticoid receptors within] and the Serotonin (5-HT) system. We found that as adults, male Sprague-Dawley pups treated with GC showed agent specific altered growth, anxiety-related behavior, changes in corticoid response to novelty and gene expression changes within LHPA and 5-HT-related circuitry. The data suggest that prolonged GC-receptor stimulation during the early neonatal period can contribute to the development of individual differences in stress response and anxiety-related behavior later in life.

Germinal matrix haemorrhage: destroying the brain's building blocks

The most skilled stonemasons cannot construct a cathedral without an ample supply of fine granite blocks. Likewise, the human brain cannot be built properly if stocks of neuroglial progenitors (the building blocks of the brain) are depleted by injury during the critical period of progenitor cell proliferation and migration, as occurs in germinal matrix haemorrhage in prematurity. The article by Prof. Marc Del Bigio (2011), representing the analysis of a career-spanning autopsy cohort of preterm infants with and without germinal matrix haemorrhage, he addresses a persistent clinical concern facing paediatric specialists caring for survivors of prematurity: what are the consequences of germinal matrix haemorrhage on normal brain development at the microanatomic level, and do they explain observed neurodevelopmental and neuroimaging outcome data? As a serious complication of prematurity, germinal matrix haemorrhage and its frequent accompaniment, intraventricular haemorrhage, have been recognized in the medical literature since the turn of the last century (Corvelaire, 1903). In the period from 1940 to 1970, population studies identified the maternal, obstetric and neonatal risk factors for development of germinal matrix haemorrhage, including vaginal delivery, low birth weight, low Apgar scores, hypoxia and hypercapnea (Bassan, 2009; Ballabh, 2010). Improvements since the 1970s in neonatal intensive care have reduced the incidence of cardiorespiratory complications and increased survival following preterm delivery; however, the overall incidence of intraventricular haemorrhage in very low birth weight infants has remained static over the last two decades (Jain et al. , 2009). Thus, intraventricular haemorrhage is still a significant problem affecting >12 000 infants per year in the USA …