Survivors Of Neonatal Intensive Care Research Articles

Polymorphisms of Vascular Endothelial Growth Factor and Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a major problem among preterm survivors of neonatal intensive care. Neovascularization of the retina is prominent in the proliferative stages of ROP and is under the control of factors such as vascular endothelial growth factor (VEGF). The authors investigated the association of ROP with VEGF genetic polymorphisms and clinical (maternal, perinatal, neonatal) risk factors among preterm infants admitted to the neonatal intensive care unit. The frequencies of VEGF 634 C/G and VEGF 936 C/T polymorphisms were determined in DNA from 102 preterm infants by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The frequency of the VEGF 634 CG genotype was significantly higher, whereas the frequency of the VEGF 634 CC genotype was significantly lower among neonates with ROP. The frequencies of the VEGF 634 GG, VEGF 936 CC, and VEGF 936 CT genotypes were similar in both groups. The distribution of VEGF 634 G allele was significantly different between the two groups. By logistic regression analysis, low birth weight, presence of maternal disease, respiratory distress syndrome, hypotension, and VEGF 634 CG genotype remained significant risk factors for the development of ROP. The results support the hypothesis that the carrier state of VEGF 634 C/G polymorphism has an impact on the risk of ROP in infants. A broader study may suggest that this marker could be used as an indicator in the screening for ROP.

Concordance between school outcomes and developmental follow-up results of very preterm and/or low birth weight children at the age of 5 years

IntroductionLong-term follow-up studies have revealed a high frequency of developmental disturbances in preterm survivors of neonatal intensive care who were formerly considered to be non-disabled. These developmental disturbances interfere with the acquisition of everyday skills and, in particular, with normal school functioning.MethodsDevelopmental and school outcomes of 355 children, age 5 years at the time of the study, who had a mean gestational age of 30.2 weeks (SD: 1.95) and a mean birth weight of 1272 g (SD: 326) were investigated. Children with severe handicaps were excluded from the study. Perinatal data, information from a parental and school questionnaire and data from standardized developmental tests were used to explain the differences.ResultsAn agreement of 72% was found between developmental follow-up and school outcomes. Normal developmental results but problematic school outcomes were found for 15% of the children tested. There were more boys than girls in this latter group as well as small-for-gestational-age children with relatively poor motor or language development. The schools had not identified problems in 13% of the children, whereas their developmental outcomes were problematic. These children had less neonatal morbidity and relatively higher IQ’s than children who also had problematic developmental outcomes but who had been signalled as problematic by their schools.ConclusionsSchools have a good insight in the school functioning of children who are developing well and of children with the lowest developmental scores and the most complicated neonatal histories. How school and developmental outcomes interrelate in the in-between groups remains a challenging question that could be answered by following these children throughout their school career.

Long-term caring for neonates

Since the earliest days of modern neonatology, there has been concern with regard to the outcomes of high-risk survivors after they go home from the hospital. This concern has increased with the recent improvements in survival of infants of extremely short gestation who would previously have died. These issues stimulated the development of follow-up programs by neonatologists, some of them in Canada (1), who could be said to have founded the field of outcomes research. Despite the huge obstacles involved in consistently following infants through childhood, adolescence and, now, adulthood, we have had great success. The follow-up programs have produced important information based on large samples with low attrition. As a result, some programs have shown the generally positive futures of our patients, and the resilience and adaptability of the human organism (2). We have been able to describe the extent and severity of the problems that some of the infants face in the future (3), and also identify the adverse effects of some specific interventions that only became apparent in the long term (4). Neonatal follow-up programs also serve an important clinical purpose – to identify problems early, refer patients for necessary remediation and assist with the coordination of their sometimes complex care. This function is essential, and its importance has led many jurisdictions to provide funding for follow-up programs, which are recognized as an important way of improving the medical care of babies. The current issue of Paediatrics & Child Health includes a series of articles concerning neonatal follow-up, many of them focussing on the situation in Canada. Our country, with its universal health care system, has proved itself capable of ensuring that all of its neonates have the best available care, regardless of parental resources. This system has supported neonatal follow-up programs of extremely high quality, of which we can all be proud, and with outcomes that are as good as anywhere else in the world. What about the future? Stable, secured funding will allow these essential services to focus on providing excellent care and high-quality information. An extension of follow-up programs to other categories of infants is clearly important. The improved survival of infants with congenital anomalies and complex neonatal care unrelated to prematurity requires that they also benefit from the expertise of these programs. There are as many survivors of neonatal intensive care with long-term sequelae as a result of perinatal hypoxic-ischemic encephalopathy at term as there are from prematurity (5); these infants require coordinated care, and the development of effective therapies for them (6) will require ongoing outcomes research. There is also a need for further refining what should be measured and when – both as a means of identifying the child who may benefit from specific intervention and as a way of predicting the likely outcome. Collating results from across the country to develop truly regional and national statistics will provide more essential information on the effects of neonatal diseases and the best ways to improve outcomes. Improving long-term outcomes is now recognized as the most important primary objective of neonatal clinical trials, with the quality of life of the survivors of intensive care being the critical demonstration of the usefulness of an intervention or a change in care. Interventions after the neonatal period to enhance the outcomes of at-risk infants by improving care during development have been less well investigated (7,8) but must, in the future, be thoroughly researched so that we can provide optimal outcomes for all of our patients.

Current status of neonatal follow-up in Canada

Follow-up programs in Canada collect audit and outcome research data, and provide clinical and preventive health care to extremely premature survivors and other new survivors of neonatal intensive care. Results of a 2001 to 2002 survey of Canadian follow-up programs showed a tremendous variation in the patient populations seen, the timing of visits and the evaluations performed. A description of the new Quebec consortium of follow-up programs is provided and possible future directions are discussed.

Young adult outcomes of very-low-birth-weight children

Information on the young adult outcomes of the initial survivors of neonatal intensive care has been reported from the United States, Canada, Australia, Great Britain and other European countries. The studies have varied with regard to whether they were regional or hospital-based, their birth-weight group and gestational age, rates of survival, socio-demographic background, and measures of assessment and types of outcome studied. Despite these differences the overall results reveal that neurodevelopment and growth sequelae persist to young adulthood. Very-low-birth-weight young adults have, with few exceptions, poorer educational achievement than normal-birth-weight controls, and fewer continue with post-high-school study. Rates of employment are, however, similar. There are no major differences in general health status, but the young adults demonstrate poorer physical abilities, higher mean blood pressure and poorer respiratory function. There is no evidence of major psychiatric disorder, although anxiety and depression are reported more often. The young adults report less risk-taking than control populations. They report fairly normal social lives and quality of life. When differences are noted they are usually due to neurosensory disabilities. Longer-term studies are needed to evaluate ultimate educational and occupational achievement. It will also be important to assess the effects of preterm birth, early growth failure and catch-up growth on later metabolic and cardiovascular health.

UK population based study of severe retinopathy of prematurity: screening, treatment, and outcome

Background: Retinopathy of prematurity (ROP) is one of the few causes of childhood blindness in which severe vision impairment is largely preventable. Ophthalmic screening for ROP is required to identify...

266 Academic Achievement in 19 Year Old Adolescents, Born As Preterm Infants (Ga < 32 Weeks and/or Bw < 1500 Gram)

Background: In view of the increasing survival rate of very preterm and very low birth weight infants, long term outcome of these infants born in 1980's is of interest not only in terms of handicaps and disabilities but also of educational achievement. Objective: The purpose of this study was to determine the highest level of completed or current education at age 19 in adolescents born as very preterm or very low birth weight. Methods: In 1983 94% of the infants born alive in the Netherlands with a gestational age less than 32 weeks or a birth weight less than 1500 grams were included in the POPS-study (Project on Preterm and Small for gestational age infants). All 959 surviving adolescents (72% of original cohort) were invited for a full examination (including physical, mental, behavioral and educational development and social participation) in a hospital at the age of 19 years. If the adolescents refused to take part in the full assessment, they were invited to complete postal questionnaires only. Education was assessed using the same categories as the Dutch Central Bureau of Statistics (CBS) in the total population at the same age (reference category). Results: There were 596 (62%) full-responders, 109 (11%) postal responders and 254 (26%) non-responders. In non-responders we found (based on previous assessments) significantly more adolescents of non-Dutch origin and of low educated mothers, and more severe handicaps. Of 705 responders, data on education were available in 688. Of POPS-adolescents, 17% had completed special education or lower vocational training (CBS: 6%) and 9% primary school only (CBS: 6%). Secondary education had been completed or was being attended by 60% (CBS: 81%) of which 21% (CBS: 29%) was currently at university. Conclusions: Academic achievement in adolescents born very preterm or very low birth weight is significantly lower than that in the general population of the same age in the Netherlands. In view of probable positive selection bias in responders, the level of completed education in non-responders will be even lower. Social participation, future employment and independency may be difficult to achieve for many of these survivors of neonatal intensive care.

Genetic polymorphisms and retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a major problem among very preterm survivors of neonatal intensive care. Neovascularization of the retina is prominent in the proliferative stages of ROP and is under the control of several factors such as vascular endothelial growth factor (VEGF). This study was undertaken on the hypothesis that genetic polymorphisms of VEGF, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha would occur more frequently in preterm infants with progressive ROP than in those with mild or no disease. The frequencies of VEGF -634 G-->C, VEGF *936 C-->T, TNF-alpha -308 G-->A, and TGF-beta -509 C-->T were determined in DNA from 91 infants who had received treatment for threshold ROP and 97 comparison infants. The frequencies of the VEGF *936 C-->T, TNF-alpha -308 G-->A and TGF-beta -509 C-->T polymorphisms were similar in both groups. The distribution of alleles at VEGF -634 was significantly different between the two groups (P = 0.03). Homozygotes for the G allele, associated with higher VEGF production were twice as likely to have threshold ROP. The progression of ROP to threshold ROP in very preterm infants may be influenced by genetic differences in VEGF production. Future efforts at prevention of threshold ROP may be directed toward blocking excess production of VEGF.

"Benign" extra-axial fluid in survivors of neonatal intensive care.

To identify the prevalence of "benign" extra-axial fluid (BEAF), the risk factors associated with this condition, and the natural history in "graduates" of neonatal intensive care. Cross-sectional study. Neonatal follow-up clinic at a tertiary care center. Seventy-seven infants with a head circumference greater than the 95th percentile by growth percentiles from either the National Center for Health Statistics or the Infant Health and Development Program growth percentile graphs who attended the Neonatal Follow-up Program at The Children's Hospital of Philadelphia between January 1, 1998, and December 31, 2001. Bronchopulmonary dysplasia, extracorporeal membrane oxygenation; development at 18 to 24 months. There were 26 infants (34%) in the BEAF group, 43 (56%) in the control group without extra-axial fluid, and 8 (10%) in the hydrocephalus group. Compared with the control group, infants with BEAF were more likely to have bronchopulmonary dysplasia or to require use of extracorporeal membrane oxygenation in the immediate neonatal period (risk ratio, 6.1; 95% confidence interval, 1.5-29.8). Measurements of head circumference in the BEAF group showed rapid growth between 3 and 12 months, followed by growth greater than and parallel to the 95th percentile. Head circumference measurements in the control group showed continued growth along the 95th percentile for age. Infants with BEAF were more likely than controls to develop cerebral palsy (risk ratio, 9.9; 95% confidence interval, 1.3-77.9) and to have evidence of developmental delay at adjusted ages 12 and 18 to 24 months. The presence of extra-axial fluid in macrocephalic survivors of neonatal intensive care is associated with an increased risk of developmental delay and cerebral palsy compared with control macrocephalic survivors.

Pre- and postnatal factors in chronic lung disease: implications for management.

Much of the success in the field of Neonatology over the last decades is related to progress in the management of neonatal respiratory disorders. The widespread use of prenatal glucocorticoids to accelerate lung maturation, postnatal surfactant therapy, and improved methods of ventilation, have drastically improved the outlook for these infants so that preterm infants with birth weights between 500 and 750 grams have at least a 50% chance of survival.1,2 Unfortunately, chronic neonatal lung disease, more commonly known as bronchopulmonary dysplasia (BPD), develops in half of these survivors, posing a challenge for clinicians and researchers alike. When first described in 1967, BPD was thought to be a consequence of the exposure of the immature lung to barotrauma or oxygen toxicity.3 These mechanisms still apply in many preterm infants, however, BPD typically develops in the smallest, most immature survivors of neonatal intensive care, most of whom have not been exposed to barotrauma or high oxygen concentrations.4−6 These infants are diagnosed on clinical rather than pathologic criteria, and exhibit combinations of respiratory distress, hypoxemia accompanied by prolonged oxygen dependence, and hypercarbia, with episodic bronchospasm and congestive heart failure. The development of BPD is usually defined on the basis of the sustained need for supplemental oxygen at 28 days or, more commonly, 36 weeks

Development and evaluation of a follow up assessment of preterm infants at 5 years of age

Background: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled. Aims: To develop and validate an assessment tool...

A focus of care for neonatal nursing: the relationship between neonatal nursing practice and outcomes. Part 1.

The developmental outcomes of survivors of neonatal intensive care are, in part, a measurement of the quality of care provision. The relationship between neonatal nursing practice and long-term outcomes of survivors remains unclear. This study aimed to determine the focus of care currently influencing qualified neonatal nurses' practice, to ascertain if nursing care is provided in response to the developmental needs and consequent future quality of life of high risk babies. Following a detailed literature review, a case study combining semi-structured interviews with documentary evidence was undertaken within a regional neonatal intensive care unit. The primary focus for the study was the perspective of qualified neonatal nurses working in the field. This first part of a two-part report, presents the background, aims, literature review and design of the study. The findings, discussion and conclusion will be presented in the June issue.

Periventricular haemorrhage and tocolytic therapies

Advances in perinatal care in the 1990s resulted in a significant increase in the survival of preterm infants, such that in countries in which neonatal intensive care is established most babies born before term now survive.1 However, despite improved survival, preterm birth remains one of the leading causes of infant mortality.2 There is, furthermore, considerable neonatal morbidity and long-term neurodevelopmental disability among the survivors of neonatal intensive care.3

Consideration of the Use of Health Status, Functional Outcome, and Quality-of-Life to Monitor Neonatal Intensive Care Practice

Measures of health status, functional abilities, and quality-of-life are being used increasingly to evaluate health care practice, and to measure outcomes from the patient's perspective. There is thus a need to reassess the use of growth and neurodevelopmental status that have traditionally been used as measures of outcome after neonatal intensive care. The quality of neonatal intensive care constitutes only one factor among many that determine the functional health and quality-of-life of survivors of neonatal intensive care. These include genetic disposition, intrauterine events, the effects of sociodemographic factors on the health and development of the child, and on the parents' assessment of their child's functioning. To obtain health status, functional and quality-of-life measures, parents need to act as proxy for the child during infancy and childhood. The parents' cultural, social, and educational background and the specific experience of the parent with children may influence their responses. Furthermore, their perspective may differ from that of the child. Measures that have been used or have the potential to measure health status, functioning, and quality-of-life include the National Health Interview Survey, the National Health Insurance Study, the Functional Status II, the Multi-Attribute Health System, the Functional Independence Measure for Children, the Vineland Adaptive Behavior Scales, the Adolescent Child Health and Illness Profile, and the Child Health Questionnaire for children, infants, and toddlers. Knowledge of the validity of the use of these measures among survivors of neonatal intensive care is, however, sparse. Studies have shown that the collection of a standard core of data from various national sources with specific criteria for defining severe disability at 2 years of age is feasible in Great Britain. However, questionnaires or available national databases provide global and epidemiologic information on outcomes rather than identifying the specific pathogenesis or rates of impairments. To determine the possible deleterious effects of new therapies, specific diseases or impairments will need to be identified rather than the global effect on functioning or health related quality-of-life. Examination of the proximal neonatal impairments that predispose to later disability, such as rates of periventricular hemorrhage or retinopathy of prematurity, are probably better measures for evaluating quality of neonatal care rather than distal impairments such as cerebral palsy, growth impairments, or reactive airway disease. The ultimate goal of neonatal intensive care is to provide survival without impairment. Objective measures of specific impairments and their residual disability are thus better measures of the quality of neonatal intensive care than subjective assessments of children and their families.

Extremely Low Birthweight (ELBW) Infants: Follow-Up To 12.5 Years 1356

Continuing concerns have arisen regarding the quality of life for the progressively smaller and less mature survivors of neonatal intensive care, yet relatively few studies have reported outcome beyond age five. This study followed a cohort of ELBW (≤1000g) survivors from our tertiary care NICU into their intermediate school years. Of 129 ELBW admissions 1983-1985 (76% inborn), 69 (53%) survived to discharge (27%≤750g vs 70%>750g BW; p 85, without neuromotor/sensory dysfunction), 25(50%) were mildly impaired (MI) and 11 (22%) were moderately to severely impaired (MSI). The MI group included 22 with fine and/or gross motor incoordination, 11 with borderline IQ (71-85), 11 with learning problems and 4 with ADHD. Eight of the 11 MSI children (8M, 3F) had multiple disabilities including 3 with severe visual impairment, 5 with shunted hydrocephalus, 5 with CP and 9 with MR. Poorer neurodevelopmental outcomes were associated with prolonged mechanical ventilation, P-IVH, or non-Caucasian race (p<0.05). Educational status was tracked to a mean age of 12.5±1.1 yrs for 50 of the 51 children (1 MSI child lost to follow-up). Thirty-one (62%) children including the remaining 10 in the MSI group, 20 of 25 in the MI group, and 1 in the NL group were receiving special services. Fourteen children were in special self-contained class settings, and 17 were in regular classrooms with additional remedial/tutorial help and/or rehabilitation therapies. One child with learning disabilities was home schooled. While this study supports the literature showing that the majority of ELBW survivors are free of major neurodevelopmental impairments, it underscores the importance of monitoring these children well into their school years, as a large proportion have milder deficits requiring special educational assistance.

Are outcome data regarding the survivors of neonatal care available from routine sources?

AIMTo determine whether existing information and surveillance systems can be used to provide follow up data on groups of infants at increased risk of disability—for example, the survivors of neonatal...

Evaluation of neurodevelopmental outcome in highrisk infants in Australia

An understanding of the neurodevelopmental outcome of long-term survivors of neonatal intensive care is essential for the informed management of preterm or high risk infants. This annotation looks at the current status of neonatal follow-up services in Australasia and highlights problems in the collection and interpretation of data. It suggests that we should work towards achieving a consensus on standard definitions and test regimes and on national data collection.

The measurement of neonates.

Accurate measurements of both healthy and premature neonates are possible but rarely performed. Routine anthropometry is often not performed at all or with large measurement errors due to inadequate training of personnel or inappropriate equipment. Sick neonates are often considered unsuitable for anthropometry and growth is wrongly equated with weight gain. Gain in length may be disturbed by poor health and permanent extrauterine growth retardation and changes in body proportions induced in some survivors of neonatal intensive care. Drug treatments may have profound effects on length gain and the relationship of length to weight.

Health related quality of life considerations in the outcome of high-risk babies

The conventional approach for assessing the outcome of survivors of neonatal intensive care has been to report neurological sequelae and the results of psychometric tests. These evaluations provide objective measures from the perspective of health professionals without consideration of the values of children and their parents. This paper describes a new approach of measuring the health status and health-related quality of life of children and its application to a cohort of teenagers who were extremely low birthweight and a comparison group. The potential use of this approach to evaluate the impact of newer therapies or intervention programmes is discussed.

The cost of neonatal care: reviewing the evidence.

I have not done justice to the considerable amount of research that has been reported on the costs and economics of neonatal care. However, I can draw a few conclusions from this review. In spite of difference in methods, there is consistency between studies in the picture of the cost of providing neonatal care, and the relationship between costs for different groups of babies. I have reported the costs for very low birthweight babies requiring intensive care. Several authors have commented that more than half the workload in a neonatal unit is taken up by care of bigger babies and recovering survivors of neonatal intensive care. There is very little evidence about the costs of care of these babies, especially those that do not require intensive care or surgery. There is, however, increasing interest in the question of appropriate admission and discharge policies for NICUs. I have shown that the economics of NICU care may have been changed by the introduction of surfactant and by the wider use of antenatal corticosteroids.