Vineta Ruth

Cord Plasma Vasopressin, Erythropoietin, and Hypoxanthine as Indices of Asphyxia at Birth

ABSTRACT: To assess the value of cord plasma arginine vasopressin (AVP), erythropoietin (EP), and hypoxanthine (HX) as indices of asphyxia, we studied 62 infants of mothers with preeclampsia, 34 acutely asphyxiated infants, with 5-min Apgar score ≤6 and/or umbilical arterial pH ≤7.05, and 38 control infants. Umbilical arterial AVP in the asphyxia group (geometric mean; 95% confidence interval: 180; 92–350 pg/ml) was higher than in the control group (23; 8–466, p = 0.002) and correlated with umbilical arterial pH (r = −0.447, p = 0.028). AVP levels in the preeclampsia group did not differ from controls. Cord venous EP was higher in infants delivered by elective cesarean section from women with severe preeclampsia (115; 75–177 mU/ml, p < 0.001) than in control infants (23; 18–27); in the whole group EP correlated with pH (r = −0.493, p < 0.001). EP in the asphyxia group was similar (46; 35–65) to controls (40; 33–47) and did not correlate with pH. Cord arterial HX in the preeclampsia group was similar to controls (12.3; 9.5–16.0 μmol/liter), but elevated in the asphyxia group (23.7; 17.6–31.8, p = 0.001), in which HX correlated with pH (r = 0.558, p = 0.008) and AVP (r = 0.588, p = 0.005). EP did not correlate with AVP or HX in any group, nor did any of the variables correlate with the Apgar score. We conclude that cord plasma AVP and HX reflect acute asphyxia, whereas EP is elevated after more prolonged hypoxia.

Prediction of perinatal brain damage by cord plasma vasopressin, erythropoietin, and hypoxanthine values

For an assessment of whether cord plasma arginine vasopressin, erythropoietin, and hypoxanthine concentrations are predictors of perinatal brain damage, these concentrations were measured in 62 infants born after preeclampsia of pregnancy, 31 acutely asphyxiated infants, and 38 control infants. Follow-up at 2 years included neurologic examination and the determination of a Bayley mental score. Clear abnormality (death, cerebral palsy, or developmental delay) was found in four infants in the preeclampsia group and five in the asphyxia group; slight abnormality was found in 12 and 6 infants, respectively; and no abnormality was found in the remainder. Neither arginine vasopressin values nor hypoxanthine values predicted adverse outcome in either study group. A high erythropoietin level was found in infants born after preeclampsia regardless of outcome: normal outcome (geometric mean (GM), 102; 95% confidence interval [CI], 69 to 153 mU/ml), slightly abnormal outcome (GM, 100; 95% CI, 37 to 270 mU/ml) or clearly abnormal outcome (GM, 84; 95% CI, 19 to 378 mU/ml). However, asphyxiated infants with clearly abnormal outcome had higher erythropoietin values (GM, 67; 95% CI, 33 to 137 mU/ml; p less than 0.05) than the normal infants (GM, 37; 95% CI, 23 to 59 mU/ml). We conclude that a high erythropoietin level after normal pregnancy, but not after preeclampsia, indicates an increased risk for cerebral palsy or death.

Early high-dose phenobarbital treatment for prevention of hypoxic-ischemic brain damage in very low birth weight infants.

In a randomized prospective trial, we studied the effect of early high-dose phenobarbital treatment on the early (intraventricular hemorrhage) and late (neurodevelopmental abnormalities) manifestations of hypoxic-ischemic encephalopathy in preterm infants weighing 1500 g or less at birth. The first intravenous dose of 15 mg/kg was given at a mean age of 110 minutes, followed by 15 mg/kg after 4 hours and then by 5 mg/kg at 24-hour intervals for 5 days. The overall incidence of intraventricular hemorrhage was 32% in treated and 46% in control infants, a nonsignificant difference. An ultrasound brain scan at 9 months old revealed no significant difference in the incidence of ventricular dilatation between treated (19%) and control (29%) infants. At 27 months, a similar incidence of mild (10%) and severe (10%) neurodevelopmental handicaps was found in both treated and control groups. Since beneficial effects could not be documented by any of the criteria used, we conclude that routine administration of phenobarbital to low birth weight infants is not justified.

Plasma |[beta]|-Endorphin in Perinatal Asphyxia and Respiratory Difficulties in Newborn Infants

ABSTRACT. The effects of intrauterine stress and birth asphyxia on the plasma concentration of β-endorphin (β- E) in cord blood and in venous blood at the age of 2 h was investigated in newborn infants. Term infants with acute birth asphyxia (n=11), infants born to mothers with preeclampsia (n=15), and prematures with respiratory difficulties (n=4) were entered into the study. Twenty control infants were studied; 12 were born after spontaneous delivery and eight after elective cesarean section. After normal spontaneous delivery, the plasma β-E level decreased significantly, the median values being 17 pmol/ liter at birth and 9.3 pmol/liter at the age of 2 h, whereas after elective cesarean section it remained unchanged (13 and 13 pmol/liter, respectively). In acute asphyxia the plasma β-E level varied widely at birth, from 9.7 to 108 pmol/liter. At the age of 2 h, the β-E level was high (26 to 83 pmol/liter) in those asphyctic infants who required prolonged mechanical ventilation, but it fell to the range of 1.6-13 pmol/liter when the infant recovered rapidly. The β-E level was not increased in the preeclampsia group, not even in small for gestational age infants. In preterm newborn infants with respiratory difficulties, a significant postnatal rise of plasma β-E level was found, the β-E value varying from 7.3 to 16 pmol/liter at birth and from 61 to 168 pmol/liter at the age of 2 h. These results indicate that increased β-E secretion is associated with respiratory difficulties in the newborn infant.

CONGENITAL CENTRAL HYPOVENTILATION SYNDROME TREATED WITH DIAPHRAGM PACING

ABSTRACT. Congenital central hypoventilation syndrome was diagnosed in an infant who since birth had shallow respiration and CO2 retention during sleep, absent ventilatory response to hypercarbia, and no underlying disease or trauma to account for the symptoms. Diaphragm pacing was started at the age of 81/2 months and has been successfully carried out at home, guided by end‐tidal CO2 monitoring. After 22 months of home treatment, at the age of two years 9 months, linear growth and psychomotor development are progressing normally, while previous symptoms of cor pulmonale have not progressed.

Purine Metabolites and Lactate as Parameters of Hypoxia in the Newborn Infant

Summary: In order to evaluate possible biochemical parameters of tissue hypoxia, arterial samples from 29 sick neonates were taken at 6-h intervals for lactate and blood gas analyses, as well as assays of purine metabolites in plasma. The state of the infant at each sampling was arbitrarily classified as severe, moderate, or mild on the basis of Po2, pH, Fio2, and transcutaneous Po2. Of the total of 289 samples, 72 were in the mild, 178 in the moderate, and 39 in the severe category. Elevated values for hypoxanthine (>36 µmol/L), xanthine (>11 µmol/L), and lactate (>3.6 mmol/L) were defined as >2 SD above the mean of infants with slight or no hypoxia. Hypoxanthine values were elevated in 7% of mild and in 13% of severe cases whereas the corresponding incidences for elevated xanthine values were 1 and 8%, and for elevated lactate values 7 and 39%. Conversely, when hypoxanthine was elevated (n=21), mild hypoxia was present in 24% and severe in the same percentage of cases whereas the corresponding incidences for elevated xanthine (n=7) were 14 and 43% and for lactic acid (n=41) 12 and 37%. No consistent differences in plasma uric acid levels were noted between the mild and severe cases of hypoxia. We conclude that neither purine metabolites nor lactic acid concentrations in intermittent samples of arterial blood are reliable indicators of tissue oxygenation in the newborn.

61 HIGH-DOSE PHENOHARGITAL TREATMENT TO PREVENT POSTASPHYXIAL BRIAN DAMAGE: A 6-YEAR FOLLOW-UP

Aim: To evaluate in a randomized controlled trial if high-dose phenobarbital (PB) improves outcome after severe asphyxia.Patients: Newborn infants with a 5-min Apgar score 0-3 or need for ventilatory assistance >30 min after birth were allocated to the treatment (PB+, n=21, mean gestational age 38.6; SEM 0.6 wk) or control group (PB+, n=17, 38.7; 0.6 wk).Intervention: PB 30 mg/kg was given iv before the age of 4h, a second dose 15 mg/kg iv 4h later to reach a serum level of 200-300 μmol/l, thereafter 5 mg/kg/d for 5 days.Follow-up results: Of the 21 PB+ infants, there were 4 neonatal deaths, 4 CP (1 late death), and of the 17 PB- infants, 3 deaths, 2 CP (NS). At 6 yrs of age, the mean IQ (WISC-r) was 108 (95%CI: 99-117) in PB+ are 111 (97-125, NS) in PB- testable infants. The groups performed similarly in the neuropsychological tests: copying design (VMI), attention and confrontation naming (NEPSY). Including all outcome criteria on a quality-of-life scale ranging fom 0 (dead) to 1 (perfect health), the mean score in PB+ infants (0.500; 95%CI:0.328-0.672) did not differ from PB- (0.559; 0.368-0.750) infants.Conclusion: PB does not prevent postasphyxial brain damage.

Purine Metabolites as Measures of Birth Asphyxia and Predictors of Brain Damage

The term asphyxia is generally used to describe the combination of hypoxia, hypercarbia, and ischemia. This situation may have an acute onset as a result of delivery complications, or it may be a chronic condition, usually caused by placental dysfunction. Asphyxia occurs in 1–7% of all deliveries. The major neurologic sequelae of asphyxia frequently cause a handicap and consist of cerebral palsy, hydrocephaly, and seizure disorders. In a population-based study, the incidence of cerebral palsy of perinatal origin was 1.1 per 1000 live births, and 47% of the handicapped infants had been born at term (Hagberg et al. 1984).

124 PREVENTION OF HYPOXIC-ISCHEMIC CEREBRAL DAMAGE IN PRETERM INFANTS BY PHENOBARBITAL

We evaluated the effect of phenobarbital (PB) on two sequelae of hypoxic-ischemic insult in prematures, early intraventricular hemorrhage (IVH) and late handicap due to neuronal damage. Infants weighing ≤1500g admitted before 4 hr of age were randomly assigned into a phenobarbital group (PB+), to receive 15 mg/kg iv twice at a 4 hr interval, followed by 5 mg/kg every 24 hr for 5 days, or into a control group (PB-). 45 infants were enrolled into the PB+ and 49 into the PB- group; 7 PB+ and 3 PB- infants died neonatally. IVH was diagnosed by ultrasound (US) in 13 PB+ infants (29%), 4 of them severe (grades III-IV). 28 PB- infants (57%) had IVH, 7 of them severe. Overall incidence of IVH was significantly higher in the PB-group α2=8.8, p<0.01), but when considering only severe IVH there was no significant difference between the groups. At follow-up 13 (39%) PB+ and 17 (40%) PB- infants had ventricular dilatation on US; marked dilatation or hydrocephalus was found in 5 PB+ and 12 PB- infants (NS difference). Neurodevelopmental status at 15 months of age revealed mild abnormality in 4 (11%) PB+ and 4 (9%) PB- infants, whereas it was clearly abnormal in 5 (14%) PB+ and 4 (9%) PB- infants.Our results indicate that early high-dose PS-treatment of small prematures decreased the incidence of mild to moderate IVH. However, follow-up so far has failed to show a difference between treatment and control groups in neurodevelopmental outcome or incidence of ventricular dilatation. Routine administration of PB to small prematures cannot be recommended.

PREMATURE BIRTH OVER 20 YEARS

The risk factors for premature birth were evaluated with an interval of 20 years. The study population comprises two one-year cohorts of parturients (n=21430) and births (n = 21710) for years 1966 and 1966. the infants burn from multiple pregnancies, infants with unknown gestational age and the prematures delivered after elective caesarean section or induced labour were excluded, which leaves infants for the 1966 and 1985 for 1985/86 cohort. Among the 1966 cohort 9 % while among 1985/86. 72% of the mothers to 1966 had passed only elementary school, while in later 1985/86 cohort 28 %. The association of prematurity and different biological factors was studied using a logistic regression model and stratification with respect to sociodemographic factors. In both cohorts placental abnormalities, vaginal bleeding, earlier low birth-weight baby and the most disadvantageous sociodemographic group were associated with prematurity. In 1966 also age under 20 and in 1985/86 cohort malformations, hypertensive disorders and smoking increased the risk of premature labour. The study showed that the incidence of prematurity has decreased by more than half over 20 years, the families social wellbeing has increased and that the effect of social factors on prematurity to less important. The biological factors are mainly are mainly the same and have the most important effect on the risk of the premturity.