Thyroid function in healthy and sick very-low-birth-weight infants--thyrotropin and free thyroxine levels until the sixth week of age.

Hypothyroxinemia in preterm infants without congenital hypothyroidism is associated with developmental delay. Longitudinal information on thyroid function in very-low-birth-weight (VLBW, <1,500 g birth weight) infants is limited: we present data on thyroid function in sick and healthy VLBW infants until 6 weeks of age. Free T(4) and TSH levels routinely obtained on days 14-21 and days 35-49 in 92 consecutive VLBW infants were correlated retrospectively with neonatal morbidity. Free T(4) levels were positively correlated with gestational age; an independent effect of neonatal disease on thyroid function was not detectable.

Thyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide.

BACKGROUND: Thyroid function disorders have often been observed in preterm infants after intravenous administration of iodinated contrast medium. The effect on thyroid function depends on the dosage, but the choice of the contrast medium may be equally important, as there are appreciable pharmacological differences between them. METHOD: Thyroid function was analysed in 20 very low birthweight infants of gestational age less than 30 weeks after injection of iopromide, a monomeric non-ionic iodinated contrast medium. Levels of free thyroxine and thyroid stimulating hormone were compared with those in 26 control infants. RESULTS: Free thyroxine levels in all study infants ranged from 9.0 to 25.7 pmol/l (days 14-21) and 9.0 to 23.2 pmol/l (days 35-49), and thyroid stimulating hormone levels ranged from 0.13 to 0.26 mU/l (days 14-21) and 0.26 to 11.11 mU/l (days 35-49). These levels were not altered after injection of iopromide. CONCLUSION: The risk of transient hypothyroidism or hyperthyrotropinaemia may be reduced with the use of iopromide compared with other contrast media.

Neonatal outcome in small for gestational age infants: do they really better?

BACKGROUND: There still is a controversy as to the neonatal outcome of small for gestational age (SGA) infants compared to a appropriate for gestational age (AGA) preterm infants. As a part of a randomized multicenter trial on timing of bovine surfactant therapy, we aimed at investigating short-term outcome variables in SGA-infants compared with AGA-infants. METHODS: SGA-infants were classified weighing below the 10th percentile at birth and were compared to AGA-infants in terms of prenatal and neonatal characteristics and neonatal outcome. RESULTS: A total of 317 infants were enrolled, 59 SGA- and 258 AGA-infants. Both groups did not differ in gestational age, however, SGA-infants had a lower birth weight. Preterm premature rupture of fetal membranes was observed more frequently in AGA-, preeclampsia in SGA-infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary airleaks and days on the ventilator did not differ between both groups. However prolonged nasal CPAP, supplemental oxygen therapy and chronic lung disease at 28 days and 36 weeks was diagnosed more often in SGA-infants. Furthermore mortality was significantly higher in SGA-infants as well as total NICU and total hospital days. CONCLUSION: As SGA-infants have an increased mortality rate and an increased risk for developing chronic lung disease, further studies should focus on prevention of intrauterine growth restriction and its complications.

Early versus late surfactant treatment in preterm infants of 27 to 32 weeks' gestational age: a multicenter controlled clinical trial.

OBJECTIVE: To investigate whether early (<1 hour after birth) surfactant administration would be superior to late treatment (2-6 hours after birth) in preterm infants. STUDY DESIGN: Randomized controlled multicenter clinical trial. PATIENTS AND METHODS: Prenatal randomization of all infants of 27 to 32 weeks' gestational age stratified by center after parental informed consent. Early treatment: 100 mg/kg body weight bovine surfactant (SF-RI1, Alveofact; Dr K. Thomae, Biberach, Germany) to infants requiring intubation after birth. Late treatment: identical dosage to infants requiring intubation up to 6 hours of age with the fraction of inspired oxygen >0.4 at 2 to 6 hours after birth. Primary endpoint: the time on mechanical ventilation. Main secondary endpoints: mortality, bronchopulmonary dysplasia, intraventricular hemorrhage >/=grade III, and periventricular leukomalacia. Sample size calculation: at least 280 infants to prove superiority of either approach (alpha = 0.05; beta = 0.90). RESULTS: Enrollment of 317 infants, 154 randomized to early surfactant treatment, 163 to late surfactant treatment. Study infants (all following data intent-to-treat groups: early versus late surfactant) were similar with respect to: gestational age, 29.5 +/- 1.6 weeks versus 29.7 +/- 1.6 weeks; birth weight, 1227 +/- 367 g versus 1269 +/- 334 g; and the rate of prenatal corticosteroids, 79.9% versus 72.8%. Duration of mechanical ventilation: 3 days (0-8) versus 2 days (0-6) (median, interquartile); further outcome variables: death or bronchopulmonary dysplasia (day 28) 25.9% versus 23.9%, mortality 3.2% versus 1.8%, intraventricular hemorrhage >/=grade III 6.5% versus 3.7%, and periventricular leukomalacia 5.2% versus 5.5% not differing statistically. CONCLUSION: In preterm infants with a high rate of prenatal glucocorticoids, early surfactant administration was not found to be superior to late treatment in terms of relevant outcome variables.

The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin Study Group.

BACKGROUND: Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions. METHODS: We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward. RESULTS: The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02). CONCLUSIONS: Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.

High-dose versus low-dose bovine surfactant treatment in very premature infants.

The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low-dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24-29 weeks and birth weight 500-1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO2) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO2/FiO2) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25% improvement in the endpoint. Oxygenation was improved significantly with high-dose (n = 42) compared to low-dose treatment (n = 48): 30.9 +/- 15.0 kPa (231.5 +/- 112.7 mmHg) versus 24.1 +/- 15.7 kPa (180.6 +/- 118.0 mmHg) (mean +/- SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high-dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response.

Early treatment of respiratory distress syndrome with bovine surfactant in very preterm infants: a multicenter controlled clinical trial.

OBJECTIVE: To determine the effect of bovine surfactant (SF-RI 1, Alveofact) administered during the first hour following birth to very premature infants [gestational age (GA), 25-30 weeks] in a multicenter, controlled trial. HYPOTHESIS: Survival without bronchopulmonary dysplasia (BPD; definition: ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration) at day 28 is increased in surfactant-treated infants (sequential analysis). PATIENTS AND METHODS: Thirty-four infants [GA 28.0 +/- 1.5 SD weeks, birth weight (BW), 1,048 +/- 299 g] received 50 mg/kg BW surfactant, whereas 35 infants (GA, 27.6 +/- 1.5 weeks, BW 969 +/- 269 g) served as controls. Retreatment with surfactant (up to three identical doses) 12-24 hours after the previous dose was permitted if FiO2 was greater than 0.5. RESULTS: Survival without BPD was significantly higher in surfactant treated infants (26/34) compared to controls (14/35; P = 0.003), but in the incidence of pulmonary air leaks, patent ductus arteriosus, intracranial hemorrhage, and nosocomial infections they were not different. CONCLUSION: Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome (RDS).

[The effect of bovine surfactant in premature infants with respiratory distress syndrome. Results of an open, multicenter study]. / Die Wirkung eines bovinen Surfactant bei Frühgeborenen mit Atemnotsyndrom. Daten einer offenen, multizentrischen Studie.

We investigated the effects of a bovine surfactant (SF-RI 1, Alveofact) in very low birth weight infants (VLBW, b.w. 500-1500 g) with established respiratory distress syndrome (RDS; definition: FiO2 greater than or equal to 0.6 or peak inspiratory pressure greater than 22-28 cm H2O). Fifty mg/kg b.w. bovine surfactant was administered intratracheally as a bolus, if the acute response was unsatisfactory (FiO2 greater than 0.5), further administrations of surfactant up to a maximum cumulative dose of 200 mg/kg b.w. were permitted. One hundred and sixty-four VLBW infants (gestational age 28.0 +/- 2 wks; b.w. 1054 +/- 251 g; mean +/- SD) with a mean FiO2 of 0.84 +/- 0.15 were enrolled in the study. Maximum improvement in oxygen requirements was observed 1/2 h post administration (FiO2 0.53 +/- 0.22); incidence of complications during the neonatal period: pulmonary interstitial emphysema 26%, pneumothorax 10%, patent ductus arteriosus 37%, intracranial hemorrhage 47%. The overall survival rate was 61%, survival rate without bronchopulmonary dysplasia (BPD) was 47%. A multiple regression analysis was performed in order to identity factors determining survival without BPD (p less than or equal to 0.05). We observed a positive correlation for gestational age and birth weight and a negative correlation for pretreatment oxygen requirements. For further optimizing surfactant-therapy in VLBW infants with RDS, studies are mandatory using intervention criteria at lower FiO2-values and higher initial doses of bovine surfactant.

Does prophylactic use of bovine surfactant change drug utilization in very premature infants during neonatal period?

The efficacy of a bovine surfactant preparation (SF-RI 1) to increase survival without bronchopulmonary dysplasia (BPD) was studied in very premature infants in a multicenter, randomized sequential trial. Thirty-four infants were randomized to surfactant treatment, whereas 35 infants served as controls. As part of the study, pharmacotherapy with antibiotics, sedatives, catecholamines, diuretics, methylxanthines, mucolytics, muscle relaxants, digoxin, and indomethacin was registered during week 1 and weeks 2-4. As to the endpoint of the study a significantly increased survival rate without BPD was observed in surfactant-treated infants (76%) compared to controls (40%). Significant differences concerning drug utilization were found through week 1 with increased use of methylxanthines in surfactant-treated infants, which persisted during weeks 2-4 as well as a reduced incidence of diuretic therapy in surfactant-treated infants during weeks 2-4. These differences may be attributed to the shorter interval of mechanical ventilation in surfactant-treated infants (11 days) compared to controls (27 days), and to the above mentioned increased survival rate without BPD.

Drug utilization in very premature infants in neonatal intensive care units.

Neonatal drug utilization in very premature infants (gestational age (GA) 24-29 weeks), requiring intubation and mechanical ventilation at birth was registered as part of a multicenter controlled clinical trial of high-dose versus low-dose bovine surfactant (initial doses 100 mg/kg birth weight (b.w.) versus 50 mg/kg b.w.). Drug utilization during 4 weeks after birth was analyzed in 164 infants (mean GA 27.2 +/- 1.2 (SD) weeks, b.w. 970 +/- 145 g (SD)). More than half of the study infants received antibiotics (98.8%), sedatives and analgesics (91.5%), sodium bicarbonate (78%), solutions for volume replacement (62.8%), methylxanthines (56.7%) and catecholamines (52.4%). It may be concluded that the pattern of drug usage indicates a high incidence of proven or suspected infections and circulatory and respiratory disorders reflecting the high-risk state of study infants.

A multicenter randomized controlled clinical trial of bovine surfactant for prevention of respiratory distress syndrome.

Treatment with bovine surfactant (SF-RI 1) was shown to be efficacious in improving pulmonary function and in increasing survival rate without BPD in very premature infants. Surfactant therapy did not affect the risk of major complications of prematurity.

Partial duplication of 17p. A new chromosomal syndrome.

An inherited partial duplication syndrome of 17p is described. A comparison of the symptoms of a de novo partial duplication of 17p (Latta and Hoo, 1974) and those of our own case seems to indicate a characteristic syndrome. The main features include a small-for-date baby born at full term, small stature, microcephaly, typical facial changes, a heart defect, contractures of different joints, and deformities of the feet. The patients show severe motor and mental retardation.