Bronchopulmonary dysplasia - prevalence, severity and predictive factors in a national cohort of extremely premature infants.

AIM: To study prevalence and predictive factors of bronchopulmonary dysplasia (BPD) in a cohort of preterm infants with a high incidence of prenatal steroid and surfactant treatment. METHODS: BPD was analysed in a national cohort of infants with gestational age (GA) of 22-27 completed weeks (wks) or birth weight (BW) of 500-999 g. Of 464 infants who were transferred to a NICU, 377 infants with GA ≤ 30 wks and survived beyond 28 days were included in the study. RESULTS: Moderate or severe BPD was strongly related to GA. Of infants with GA 22-25 wks, 67.3% developed BPD compared to 36.6% at GA 26-30 wks. Overall, moderate and severe BPD was significantly more common in boys (63.3%) than in girls (36.6%) (p = 0.0004), but female gender was not a protective factor in infants with GA 22-25 wks. In multivariate analyses, BPD was significantly associated with gender, surfactant treatment and treatment for PDA. CONCLUSIONS: BPD remains a severe complication of extreme prematurity in spite of prenatal steroids and surfactant treatment. Whether associations with surfactant and PDA treatment simply reflect severity of early lung disease or have causal relationships should probably be studied in randomized controlled trials.

Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study.

AIM: To assess if growth restricted (small for gestational age, SGA) extremely preterm infants have excess neonatal mortality and morbidity. METHODS: This was a cohort study of all infants born alive at 22-27 weeks' post menstrual age in Norway during 1999-2000. Outcomes were compared between those who were SGA, defined as a birth weight less than the fifth percentile for post menstrual age, and those who had weights at or above the fifth percentile. RESULTS: Of 365 infants with a post menstrual age of <28 weeks, 31 (8%) were SGA. Among infants with a post menstrual age of <28 weeks, only chronic lung disease was associated with SGA status (OR 2.7, 95% CI 1.0 to 7.2). SGA infants with a post menstrual age of 26-27 weeks had excess neonatal mortality (OR 3.8, 95% CI 1.3 to 11), chronic lung disease and a significantly higher mean number of days (age) before tolerating full enteral nutrition. SGA infants with a post menstrual age of 22-25 weeks had an excess risk of necrotising enterocolitis. CONCLUSION: Extremely preterm SGA infants had excess neonatal mortality and morbidity in terms of necrotising enterocolitis and chronic lung disease.

Effects of selective inhibition of the endothelin A and B receptors on hypoxic pulmonary vasoconstriction in newborn piglets.

UNLABELLED: The effects on pulmonary artery pressure (PAP) and plasma Endothelin-1 (ET-1) were studied in piglets during severe hypoxemia and reoxygenation for 2 h with selective inhibition of the endothelin receptors. Two groups were subjected to selective ETA (ETA group) or ETB (ETB group) receptor inhibition. During hypoxemia there was an initial increase in PAP to 36.3 and 34.3 mm Hg in the ETA and ETB groups respectively, with a decrease to the end of hypoxemia. During reoxygenation PAP reached a maximum at 5 min with a mean of 29.6 and 38.4 mm Hg in the ETA and ETB groups respectively, and then PAP gradually declined towards baseline. During the 2 h reoxygenation period PAP was higher in the ETB group than in the ETA group (p = 0.02). Plasma ET-1 increased from 1.50 and 1.17 ng/L at baseline to 2.07 and 3.18 ng/L at the end of hypoxemia in the ETA and ETB groups respectively. CONCLUSION: ETB receptor inhibition leads to increased pulmonary vasoconstriction during reoxygenation following hypoxemia compared to ETA receptor inhibition. Not only the ETB receptor, but also the ETA receptor plays a role in maintaining plasma ET-1 levels.

Attenuated endothelin- mRNA expression with endothelin- receptor blockade during hypoxaemia and reoxygenation in newborn piglets.

UNLABELLED: We investigated the cause of decreased plasma endothelin-1 (ET-1) during hypoxaemia and reoxygenation in newborn piglets subjected to simultaneous blocking of the ET-1 receptors. Changes in plasma ET-1 and prepro-ET-1 mRNA expression in the main pulmonary artery and the left lower lobe in the lung were studied in 1-2-d-old piglets. Ten minutes prior to hypoxaemia, the hypoxaemia group (n = 10) was given saline, two groups (both n = 9) were given 1 and 5 mg/kg i.v. SB 217242 (an ET-1 receptor antagonist). Two groups served as normoxic controls, with and without SB 217242 5 mg/kg i.v. Hypoxaemia was induced by ventilating with 8% O2 until base excess was <-20 mmol/l or mean arterial blood pressure was <20 mmHg. Reoxygenation was performed for 2 h with room air. During hypoxaemia, plasma ET-1 decreased in the hypoxaemia group, remained unchanged in the 1-mg group and increased in the 5-mg group. At the end of reoxygenation, plasma ET-1 was above baseline in the 1-mg and 5-mg groups. In the pulmonary artery, the hypoxaemia group showed 2- to 5-fold higher prepro-ET- 1 mRNA expression compared to all the other groups (p < 0.05). There were trends for higher prepro-ET-1 mRNA expression in pulmonary tissue in the hypoxaemia group compared to the two receptor-blocking groups (p < 0.07). CONCLUSIONS: We conclude that hypoxaemia and reoxygenation increase prepro-ET-1 mRNA expression in the pulmonary artery in newborn piglets. These observations suggest that the half-life of ET-1 is decreased during hypoxaemia and reoxygenation in newborn piglets.

Attenuated endothelin-1 mRNA expression with endothelin-1 receptor blockade during hypoxaemia and reoxygenation in newborn piglets.

We investigated the cause of decreased plasma endothelin-1 (ET-1) during hypoxaemia and reoxygenation in newborn piglets subjected to simultaneous blocking of the ET-1 receptors. Changes in plasma ET-1 and prepro-ET-1 mRNA expression in the main pulmonary artery and the left lower lobe in the lung were studied in 1-2-d-old piglets. Ten minutes prior to hypoxaemia, the hypoxaemia group (n = 10) was given saline, two groups (both n = 9) were given 1 and 5 mg/kg i.v. SB 217242 (an ET-1 receptor antagonist). Two groups served as normoxic controls, with and without SB 217242 5 mg/kg i.v. Hypoxaemia was induced by ventilating with 8% O2 until base excess was 20mmol/l or mean arterial blood pressure was < 20mmHg. Reoxygenation was performed for 2h with room air. During hypoxaemia, plasma ET-1 decreased in the hypoxaemia group, remained unchanged in the 1-mg group and increased in the 5-mg group. At the end of reoxygenation, plasma ET-1 was above baseline in the 1-mg and 5-mg groups. In the pulmonary artery, the hypoxaemia group showed 2- to 5-fold higher prepro-ET-1 mRNA expression compared to all the other groups (p < 0.05). There were trends for higher prepro-ET-1 mRNA expression in pulmonary tissue in the hypoxaemia group compared to the two receptor-blocking groups (p < 0.07). CONCLUSIONS: We conclude that hypoxaemia and reoxygenation increase prepro-ET-1 mRNA expression in the pulmonary artery in newborn piglets. These observations suggest that the half-life of ET-1 is decreased during hypoxaemia and reoxygenation in newborn piglets.

Pulmonary hemodynamics in newborn piglets during hypoxemia and reoxygenation: blocking of the endothelin-1 receptors.

The effects of blocking endothelin (ET) receptors in pulmonary circulation during hypoxemia and reoxygenation were studied in five groups of piglets. Ten minutes before hypoxemia, the Hyp group (n = 10) was given saline and the 1-mg (n = 9) and 5-mg group (n = 9), respectively, were given 1 and 5 mg/kg i.v. SB 217242 (an ET receptor antagonist). Two groups served as normoxic controls. The piglets were ventilated with 8% O2 until base excess was <-20 mmol/L or mean arterial blood pressure was <20 mm Hg. Reoxygenation was performed with air. The increase of mean pulmonary artery pressure was significantly attenuated during hypoxemia and reoxygenation in the 1-mg group (p = 0.006). The pulmonary vascular resistance index increased significantly at the end of hypoxemia in the Hyp and 5-mg groups but was comparable to baseline in the 1-mg group. During the study period, the changes in pulmonary vascular resistance index were significantly attenuated in the 1-mg group compared with the 5-mg group. Stroke volume index was significantly attenuated compared with baseline in the 5-mg group during both hypoxemia and reoxygenation, whereas, in the Hyp and 1-mg group, stroke volume index was attenuated only at the end of hypoxemia. During hypoxemia, plasma ET-1 decreased from 1.9+/-0.2 to 1.3+/-0.3 ng/L (p = 0.008) in the Hyp group, remained unchanged in the 1-mg group, and increased from 1.6+/-0.2 to 6.6+/-1.6 ng/L (p = 0.008) in the 5-mg group. We conclude that blocking ET receptors attenuates pulmonary vasoconstriction during hypoxemia and reoxygenation in piglets.

Sodium nitroprusside prevents oxygen-free-radical-induced pulmonary vasoconstriction in newborn piglets.

The aim of the present study was to test whether hypoxanthine-xanthine oxidase (XO) induced a pulmonary vasoconstriction in newborn piglets, and whether this vasoconstriction could be attenuated or abolished by pretreatment of nitric oxide (NO) donor sodium nitroprusside (SNP). Twenty-five anesthetized newborn piglets (1-3 days old) were randomly assigned to the following four groups: the control group received saline intravenously only; the XO group received 0.1 mmol/kg of hypoxanthine subsequent with XO (1.5 U/kg); the SNP group received the same dosages of hypoxanthine/ XO together with SNP intravenously, allopurinol (ALP) group received ALP intravenously prior to hypoxanthine and XO injection. After giving XO, the pulmonary arterial pressure (PAP) and vascular resistance (PVR) increased, while the cardiac index decreased significantly in the XO group. By contrast, these variables were not significantly modified by XO injection in the SNP and ALP groups. The data suggest that oxygen free radicals induce a pulmonary vasoconstriction in newborn piglets, and this vasoconstriction can be prevented by infusion of the NO donor SNP.

Pulmonary hemodynamics and plasma endothelin-1 during hypoxemia and reoxygenation with room air or 100% oxygen in a piglet model.

The immediate effect on the pulmonary circulation of reoxygenation with either room air or 100% O2 was studied in newborn piglets. Hypoxemia was induced by ventilation with 8% O2 until base excess was <-20 mmol/L or mean arterial blood pressure was <20 mm Hg. Reoxygenation was performed with either room air (n = 9) or 100% O2 (n = 9). Mean pulmonary artery pressure increased during hypoxemia (p = 0.012). After 5 min of reoxygenation, pulmonary artery pressure increased further from 24 +/- 2 mm Hg at the end of hypoxemia to 35 +/- 3 mm Hg (p = 0.0077 versus baseline) in the room air group and from 27 +/- 3 mm Hg at the end of hypoxemia to 30 +/- 2 mm Hg (p = 0.011 versus baseline) in the O2 group (NS between groups). Pulmonary vascular resistance index increased (p = 0.0005) during hypoxemia. During early reoxygenation pulmonary vascular resistance index decreased rapidly to values comparable to baseline within 5 min of reoxygenation in both groups (NS between groups). Plasma endothelin-1 (ET-1) decreased during hypoxemia from 1.5 +/- 0.1 ng/L at baseline to 1.2 +/- 0.1 ng/L at the end of hypoxemia (p = 0.003). After 30 min of reoxygenation plasma ET-1 increased to 1.8 +/- 0.3 and 1.5 +/- 0.2 ng/L in the room air and O2 groups, respectively (p = 0.0077 in each group versus end hypoxemia; NS between groups). We conclude that hypoxemic pulmonary hypertension and plasma ET-1 normalizes as quickly when reoxygenation is performed with room air as with 100% O2 in this hypoxia model with newborn piglets.

Hypoxemic resuscitation in newborn piglets: recovery of somatosensory evoked potentials, hypoxanthine, and acid-base balance.

We tested the hypothesis that hypoxic newborn piglets can be successfully resuscitated with lower O2 concentrations than 21%. Severely hypoxic, 2-4-d-old, anesthetized piglets were randomly divided into five resuscitation groups: 21% O2 (n = 10), 18% O2 (n = 9), 15% O2 (n = 9), 12% O2 (n = 8), all normoventilated, and a hypoventilated 21% O2 group (PaCO2; 7.0-8.0 kPa, n = 9). Base excess (BE) reached -20 +/- 1 mmol/L at the end of hypoxia. After 3 h of resuscitation, BE had risen to -4 +/- 1 mmol/L in the 21% O2, 18% O2, and hypoventilated groups, but was -10 +/- 2 mmol/L in the 15% O2 group (p < 0.05 versus 21% O2 group) and -22 +/- 2 mmol/L in the 12% O2 group (p < 0.05 versus 21% O2 group). Four animals died during resuscitation, all allocated to the 12% O2 group (p < 0.05 versus 21% O2 group). Somatosensory evoked potentials (SEPs) recovered in 39 of 45 piglets, and remained present during resuscitation in all except the 12% O2 group. SEP recovered initially even in six of eight animals in the 12% O2 group, but disappeared again in all later during resuscitation. The SEP amplitude recovered to levels not significantly different from the 21% O2 group in all groups except the 12% O2 group. Plasma hypoxanthine concentrations and extracellular hypoxanthine concentrations in the striatum decreased during resuscitation to levels not significantly different from the 21% O2 group in all but the 12% O2 group (p < 0.05 versus 21% O2 group). In conclusion, severely hypoxic newborn piglets were resuscitated as efficiently with both hypoventilation and 18% O2 as with 21% O2.

Respiratory syncytial virus pneumonia ventilated with high-frequency oscillatory ventilation.

Four infants below 6 months of age with proven respiratory syncytial virus infection in need of assisted mechanical ventilation were successfully treated by high-frequency oscillatory ventilation. One of the four infants fulfilled the criteria for extracorporeal membrane oxygenation before the start of oscillation, and one on the second day on high-frequency oscillatory ventilation. However, extracorporeal membrane oxygenation was not needed in any of the infants. All survived, and three appeared to be without any pulmonary sequelae.

[Hereditary intrahepatic cholestasis with lymphedema--Aagenaes syndrome]. / Arvelig intrahepatisk gallestase med lymfødem--Aagenaes' syndrom.

Hereditary intrahepatic cholestasis with lymph oedema is now a well defined autosomal recessive inherited syndrome. More than 75% of the known cases (about 40) are Norwegian, and most of these came from a few communities in the south-western part of Norway. Cholestasis is present prior to or shortly after birth. With modern treatment the cholestasis usually improves considerably during the first two years of life, but periods of recurrent cholestasis occur later. In some cases, lymph oedema is present at birth, but usually comes to light during childhood. Lymph oedema needs continuous treatment. As a rule, the prognosis for the liver disease is good, but cirrhosis has developed in about 15% of the Norwegian cases. As for the pathogenesis of the cholestasis, the hypothesis is that the cause is an anomaly of the lymph function.

[Perinatal HIV-infection. Epidemiologic, social and ethical aspects]. / Perinatal HIV-smitte. Epidemiologiske, sosiale og etiske aspekter.

More HIV-infected women are becoming pregnant and delivering their baby. The rate of perinatal transmission is about 30-40%. Two thirds of the verified HIV-positive Norwegian women are infected by heterosexual contact. For this reason the obstetric interview is of major importance in order to identify women at risk. We discuss the HIV-screening programme now being run in Norway. Approximately 250,000 pregnant women have been tested and only 19 HIV-positive women have been detected. We discuss the ethical and social problems connected with day care centres, information to health services and the problems that arise when the mother or both parents develop AIDS and die.

[Perinatal HIV-infection. Symptomatology, diagnosis and treatment]. / Perinatal HIV-infeksjon. Symptomatologi, diagnostikk og behandling.

Perinatally acquired HIV-infection is an increasing problem. Nine infants were born of HIV-infected mothers in Norway in 1988, and ten in 1989. Pediatric AIDS may involve a wide spectrum of clinical diseases with a high affinity to the central nervous system. The time from birth to development of clinical symptoms is relatively short. The overall mortality rate is extremely high in all age groups. Two children with perinatal HIV-infection are discussed in light of our treatment regimen. Children with immunosuppression and/or clinical symptoms are treated with zidovudine (azidotymidin/AZT) perorally. Children with repeated bacterial or opportunistic infections are also given immunoglobulin intravenously every 3rd to 4th week.

Right-sided microtia and conductive hearing loss with variable expressivity in three generations.

Familial cases of microtia and meatal atresia are rare, and both dominant and recessive inheritance have been suggested. We here report a family with right-sided external ear malformations and conductive hearing loss in a grandfather, his daughter and granddaughter. The grandfather and the granddaughter both had microtia and meatal atresia, whereas the daughter had a normal outer ear except for a narrow meatus and auricular appendages. The pedigree suggests autosomal dominant inheritance with variable expressivity.

[Clinical manifestations caused by group A streptococci]. / Kliniske sykdomsbilder forårsaket av gruppe A-streptokokker.

We describe the symptomatology of different disease entities caused by group A beta-hemolytic streptococci (Streptococcus pyogenes, GAS). The case histories of four patients, two of whom died, emphasize the severity of certain clinical manifestations of GAS-infections. A 34 year-old woman was admitted to hospital four days after start of the symptoms. She presented a clinical picture very similar to that observed in fulminant meningococcal septicaemia; i.e. extensive skin haemorrhages, circulatory collapse, and multiple organ failure. She died within 12 hours of admission. GAS were isolated in blood culture. A seven day-old girl died before admission to hospital. GAS were isolated in blood cultures, cerebrospinal fluid and from her nose and throat. An eight year-old, psychomotoric retarded girl developed a severe left-sided pneumonia, empyema and scarlatina. GAS were detected in throat culture. She responded poorly to high doses of benzylpenicillin given intravenously. She recovered rapidly after thoracotomy and decortication of her left lung. Finally, we describe the case of an 11 year-old boy with rheumatic fever without cardiac involvement. The reported cases underline the need for careful diagnosis and penicillin treatment in cases of GAS-infections.