The INNOVO multicentre randomised controlled trial: neonatal ventilation with inhaled nitric oxide versus ventilatory support without nitric oxide for severe respiratory failure in preterm infants: follow up at 4-5 years.

BACKGROUND: Trials of inhaled nitric oxide (iNO) used short term in preterm infants with severe respiratory failure have to date shown no evidence of benefit, and there have been no trials reporting follow-up to 4 years of age. The INNOVO trial recruited 108 infants (55 iNO arm and 53 controls) from 15 neonatal units. By 1 year of age 59% had died, and 84% of the survivors had signs of impairment or disability. OBJECTIVE: This paper reports the long-term clinical effectiveness and costs of adding NO to the ventilator gases of preterm infants with severe respiratory failure. PATIENTS AND METHODS: Children were assessed at age 4-5 years by interview, examination, cognitive and behavioural assessments. The outcome data were divided into seven domains and were described as normal, impaired or disabled (mild, moderate or severe) by the degree of functional loss. RESULTS: 38 of the 43 survivors had follow-up assessments. In the iNO group 62% (34/55) had died or were severely disabled, compared to 70% (37/53) in the no iNO group (RR 0.89, 95% CI 0.67 to 1.16). There was no evidence of difference in the levels of impairment or disability between the two groups in any of the domains studied, or of cost differences, amongst the survivors. CONCLUSION: For this group of babies with severe respiratory failure there was no evidence of difference in the longer-term outcome between those babies allocated to iNO and those who were allocated to no iNO. The challenge is to identify those premature babies who are able to respond to NO with clinically important health improvements. TRIAL REGISTRATION NUMBER: 17821339.

Educational and behavioural problems in babies of 32-35 weeks gestation.

AIM: To identify incidence of school and behaviour problems at age 7 years in children born between 32 and 35 weeks gestation, and investigate perinatal risk factors. METHOD: The study population consisted of all children born at 32-35 weeks gestation to mothers resident in Oxfordshire in 1990. General practitioners, parents, and teachers were asked about health, behaviour, and education by postal questionnaire. Teachers rated children on level of function in six areas using a five point scale. They also completed the Strengths and Difficulties behaviour questionnaire. Perinatal risk factors were identified for children with poor school performance using a univariate and multivariate analysis. RESULTS: Teacher responses were obtained for 117 (66%) of the 176 children in the cohort. Twenty nine (25%) required support from a non-teaching assistant, five (4%) had required a statement of special educational needs, and three (3%) were at special school. Poor outcome was reported for 32% in writing, 31% in fine motor skills, 29% in mathematics, 19% in speaking, 21% in reading, and 12% in physical education. On the behaviour questionnaire, 19% of the cohort achieved an abnormal hyperactivity score (population norm 10%). Multivariate analysis showed perinatal variables that remained significant, independent of other variables; they were discharge from the special care baby unit > 36 weeks postconceptional age (odds ratio 4.15; 95% confidence interval 1.43 to 12.05) and male sex (odds ratio 3.88; 95% confidence interval 1.42 to 10.6). CONCLUSION: Up to a third of children born between 32 and 35 weeks gestation may have school problems. As there are larger numbers in this gestational category compared with smaller babies, this finding has implications for educational services.

Congenital diaphragmatic hernia: prenatal diagnosis, outcome and continuing morbidity in survivors.

OBJECTIVE: To improve counselling by investigating the prenatal diagnosis, outcome and morbidity in survivors of congenital diaphragmatic hernia. SETTING: Prenatal Diagnosis Unit, Oxford Radcliffe Women's Centre, Oxford. DESIGN: Cohort study. SAMPLE: Babies with congenital diaphragmatic hernia diagnosed postnatally and born to women scanned prenatally identified between January 1991 and December 1996. METHODS: Associated anomalies, outcome of pregnancy and final diagnoses were determined from hospital records. A report from the general practitioner and paediatrician recorded health and development information. MAIN OUTCOME MEASURES: Accuracy of prenatal diagnosis, survival of cases of congenital diaphragmatic hernia and presence of ongoing morbidity in survivors. RESULTS: There were 35 pregnancies with congenital diaphragmatic hernia, nine of which were not diagnosed prenatally. In 22 pregnancies with isolated congenital diaphragmatic hernia, four were terminated, there were six perinatal deaths and two later deaths. Thirteen of 35 cases (37%) with congenital diaphragmatic hernia were associated with other abnormalities: four with abnormal karyotype and nine with other structural anomalies. Five of these women continued with their pregnancy; there were two neonatal deaths and three survivors. Thirteen of 35 infants (37%) survived, eight with chronic disorders requiring specialist intervention including respiratory problems (n = 6); developmental delay (n = 4); poor growth (n = 5); artificial feeding (n = 3); gastro-oesophageal reflux (n = 3); recurrent hospital admissions (n = 6); and further surgery (n = 4). CONCLUSIONS: The survival for infants born alive with congenital diaphragmatic hernia was 56% (13/23), 61% of whom have persistent disorders. Despite advances in neonatology there is a high mortality and morbidity with congenital diaphragmatic hernia. Prenatal counselling should reflect this.

The effect of streptozotocin diabetes on insulin binding by isolated rat kidney tubules.

Preparations of kidney tubules were isolated from rat kidney cortex and were demonstrated to possess specific binding sites for insulin. The binding was time-and temperature-dependent and the label was displaced by bovine insulin, A1-B29 dodecoyl insulin, proinsulin and insulin A- and B-chains in proportion to their relative activity. Cell-associated degradation was studied by incubating tubules in the presence of fatty-acid-free albumin. The tubules showed high insulin-degrading activity, which was dependent on temperature, time and cell concentration. The number and affinity of insulin receptors on tubules isolated from kidneys taken from streptozotocin-diabetic rats was not significantly different from tubules isolated from untreated control or insulin-treated diabetic rats. Diabetes did not alter the kinetics of insulin degradation by the tubules. This lack of response by the tubules to changes in the concentration of circulating insulin supports the hypothesis that the kidneys do not play an active role in modulating the rate of insulin removal from the circulation.