Developmental regulation of the inhibitory effect of dopamine on prolactin release in the preterm neonate.

The secretion and release of prolactin from the anterior pituitary is under the tonic inhibitory control of endogenous dopamine produced in the central nervous system. Exogenous dopamine inhibits prolactin secretion by reaching the pituitary via the portal circulation, and the hypolactotropic effect of dopamine infusion has been documented in all age groups in humans. However, the maturation of lactotroph sensitivity to dopaminergic inhibition has not been studied. Therefore, we followed the changes in serum prolactin concentrations before, during, and after dopamine infusion in 19 sick preterm infants with a mean gestational age of 30.6+/-0.6 weeks during the first 3 days of life, and examined the relationship of the hypolactotropic effect of dopamine to gestational age and birth weight in this patient population. As expected, dopamine therapy resulted in a decrease in mean serum prolactin from 89.4+/-9.5 to 58.6+/-9.1 microg/l (p < 0.05) with a return of the serum prolactin concentration to the pretreatment level 2-6 h after discontinuation of drug administration (98.3+/-11.7 microg/l, p < 0.05). However, simple regression analysis of the individual data revealed that the magnitude of the dopamine-induced decrease in serum prolactin was significantly influenced by gestational age (p = 0.006) and birthweight (p = 0.037). Thus, our findings provide evidence for the maturation of pituitary lactotroph sensitivity to dopaminergic inhibition in the preterm human neonate.

Atrial natriuretic peptide, volume and blood pressure regulation during exchange transfusion of the neonates.

Plasma concentrations of atrial natriuretic peptide (ANP) and hemodynamic parameters were investigated in five premature infants undergoing exchange transfusion. Baseline values of ANP were elevated being 51.7 +/- 21.2 fmol/ml. Volume depletion by withdrawal of 10 ml blood did not cause changes in systolic blood pressure (79.4 +/- 4.3 vs 71.4 +/- 5.6 mmHg) and heart rate (115 +/- 5.2 vs 115 +/- 2.4 l/min). ANP levels in plasma remained unaltered (53.4 +/- 24.9 fmol/ml). Volume load of 10 ml blood transfusion increased central venous pressure by 33 per cent and ANP concentration in the plasma nearly by 30 per cent, while heart rate and blood pressure remained unchanged. Our data indicated that the heart of premature infant responds to acute volume load by increased ANP-release, while volume depletion seems not to influence hormone regulation.

Prevention of pulmonary complications during neonatal resuscitation.

The pulmonary functions were measured during resuscitation of eight critically ill newborns by the "Pulmonary Evaluation and Diagnostic System" (PEDS UNIT-M.A.S. Inc.) The asphyxiated infants (Apgar score 0-3; PH 6, 9) required more aggressive ventilator support than "traditional" cases. The danger of the pulmonary injuries was larger in this period. In spite of this, there were no signs of air leaks syndrome and the oxygenation was improved in every case. Worsening or improving the pulmonary mechanics it is possible to change the ventilator settings immediately. This method seems to be advisable to introduce in the everyday routine to prevent iatrogenic pulmonary complications in such critical situation--the reanimation.

[Continuous respiratory therapy of newborn and premature infants with respiratory disorders]. / Légzészavarban szenvedö újszülöttek és koraszülöttek tartós respirációs kezelése.

2216 newborns and prematures with respiratory distress of different underlying diseases were treated with long term respiratory therapy from 1. Jan. 1975 to 31. Dec. 1985. One part of the patients were born in our hospital, the other part of them were transported from outside. The rate of prematures was 81.2%. The respiratory therapy was applied in 1813 cases because of pulmonary diseases (group 1.), while in 403 cases the respiratory troubles were extrapulmonary in origin (group 2.). The diseases in the first group were as follows: hyaline membrane disease in 482 cases (27.30%), intrauterine pneumonia in 634 cases (34.64%), postnatal pneumonia in 291 cases (15.90%), meconium aspiration syndrome in 110 cases (6.01%), severe RDS-II in 158 cases (8.63%), pulmonary immaturity in 116 cases (6.35%), persistent fetal circulation in 21 cases (1.15%) and pulmonary aplasia on the left in 1 case (0.021%). In the second group the greatest part of the cases were treated for neurological disturbances. We discuss the indications of different types of respiratory therapy and the complications as well. The survival rate was in the first group 59.3%, while in the second only 16.9%. Therefore the respiratory therapy seems to be more effective in the pulmonary diseases of the newborns. The mortality rate and the rate of severe complications were lower among inborn babies because of the early application of the respiratory therapy.

Effect of low-dose dopamine infusion on urinary prostaglandin E2 excretion in sick, preterm infants.

In pharmacological doses dopamine (DA) will interact with several endocrine systems and both inhibit (prolactin, thyrotropin) and enhance (renin, angiotensin) hormonal release. In this study we have examined whether DA given to preterm neonates will influence prostaglandin (PG) production. The question is of importance since vasodilator PGs play a role in postnatal adaptation. We determined the effect of low dose DA infusion on the 24 h urinary PGE2 excretion rate (an index of renal PGE2 synthesis) in preterm infants. Six preterm neonates, with a 24-h requirement of 2 micrograms/kg per min DA treatment for oedema, moderate oliguria, poor peripheral perfusion and/or mild systemic hypotension were studied on days 2 (Day 1), 3 (Day 2, the day of DA infusion), and 4 (Day 3, DA discontinued) of life. Six preterm infants (control group) that did not require DA infusion were also studied to monitor possible spontaneous changes in the renal PGE2 production on days 2, 3 and 4 of life. In the control group urine output (Uv) and PGE2 excretion rate remained unchanged during the study. In the study group DA administration resulted in nearly two-fold increases in both the Uv (194%) and PGE2 excretion (182%). Urinary PGE2 excretion was, however, closely related to urine flow in both the control infants (Day 1-3) and the study group infants (Day 1-2). Since increased diuresis stimulates renal PGE2 production, our data suggest that the increased PGE2 excretion on Day 2 in the study group was not due to a direct effect of DA on PGE2 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of dopamine administration on the activity of the renin-angiotensin-aldosterone system in sick preterm infants.

Nine premature infants with birth weight of 1150 to 2500 g and gestational age of 28 to 35 weeks were given dopamine in a dose of 2-4 micrograms/kg/min to treat cardiopulmonary distress. In addition to monitoring of blood gases, blood pressure, acid-base balance, urine flow and urinary sodium excretion, plasma renin activity (PRA) and plasma aldosterone concentration (PA) was also determined prior to and during dopamine therapy. The dopamine-induced increase in urine flow and urinary sodium excretion was associated with a significant increase of PRA from 18.2 +/- 5.1 ng/ml/h to 33.0 +/- 5.6 ng/ml/h (P less than 0.025), while PA and blood pressure remained unaltered by dopamine administration. It is suggested that the angiotensin II-stimulated aldosterone production is overridden by the inhibitory effect of dopamine.

High-frequency oscillatory ventilation (HFOV) in the treatment of neonatal respiratory disturbances: case reports of two infants.

The technique of high-frequency oscillatory ventilation (HFOV) was successfully used in a preterm infant with severe hyaline membrane disease and in a term neonate presenting with intrauterine pneumonia and associated severe pneumomediastinum. None of the infants could adequately be ventilated by conventional ventilation; both of them deteriorated owing to severe hypoxaemia and hypercapnia. In the preterm infant with HMD a rapid and progressive improvement of oxygenation had been observed immediately after the beginning of HFOV, and he was successfully weaned off the ventilator after 71 hours on HFOV. His recovery was uncomplicated and definitive. In the term neonate presenting with IUP and associated severe PM, an improvement in oxygenation was detected, whereas the retention of paCO2 remained unaltered. On leaving the MAP unchanged but doubling the flow rate, paCO2 and arterial pH also normalised. No sign of PM was seen on the X-ray picture 17.5 hours after the start of HFOV. This patient was weaned off the ventilator after 29 hours on HFOV and his recovery was also uncomplicated. It is believed that recovery of the PM was secondary to the low MAP and to the higher arterial pO2 levels, and that HFOV may also have a direct role in the treatment of preexisting air leaks and perhaps also in their prevention. In our patients HFOV resulted in a definitive recovery, while no improvement had occurred on using conventional ventilation. To determine the exact mechanism of action, the clear cut fields of indications and the possible side effects of HFOV, further investigations are needed.

[Supplementation of antenatal cardiotocography (nonstress test) by nipple self stimulation]. / Ergänzung der antenatalen Kardiotokographie ohne Belastung (Non-Stress-Test) mittels Autostimulation der mütterlichen Brustwarze.

Self-stimulations of nipples were performed in 155 late pregnant women in connection with antenatal cardiotocography (nonstress test). Cardiotocographs were interpreted using an own score. Uterine contractions could be produced by nipple stimulation in 111 women (71.6 per cent). In 13 cases with score 6 to 8 these contraction contributed to explantation of fetal condition. In additional 11 cases with score 9 to 10 the attention was focussed to the reduced fetal or placental capacity by the suspect cardiotocogram. In this group frequency of caesarean section was increased significantly. In cases with successful nipple stimulation the rate of labour induction with effect was higher. Oxytocin liberation by nipple stimulation may be regarded as endogenous oxytocin stress test. This simple procedure which can be done quickly and without danger is supposed to be a good supplement to nonstress test. Its reliability can be improved and the success of induction of labour estimated.

Effect of low-dose dopamine infusion on prolactin and thyrotropin secretion in preterm infants with hyaline membrane disease.

The effect of low-dose (2-4 micrograms/kg/min) and long-term (greater than or equal to 46 h) dopamine infusion on serum prolactin and thyrotropin concentrations was investigated in 8 preterm infants with hyaline membrane disease. Dopamine was administered for systemic hypotension and/or for impending renal failure. Serum prolactin decreased from 1,314.5 +/- 422.7 microU/ml to 489.9 +/- 464.1 microU/ml (p less than 0.005), while serum thyrotropin fell from 3.77 +/- 2.27 microU/ml to 1.01 +/- 0.25 microU/ml (p less than 0.025) during dopamine infusion. Our data indicate that exogenous dopamine exerts an inhibitory effect on the secretion of prolactin and thyrotropin even in the sick preterm neonate. The role of prolactin in fetal lung maturation and in regulation of the neonatal tissue water stores is discussed. The results of the present study are also useful in explaining the renal effects of long-term low-dose dopamine infusion in the sick preterm infant.

The use of dopamine for the prevention of the renal side effects of indomethacin in premature infants with patent ductus arteriosus.

To determine if dopamine would prevent the renal side effects of indomethacin, fifteen preterm infants were randomized into two groups: seven received indomethacin alone, and eight received indomethacin together with low dose dopamine infusion. Infants who received indomethacin together with dopamine had significantly higher UV (p less than 0.005), CNa (p less than 0.005), Cosm (p less than 0.005) and FENA (p less than 0.005) than those of infants who received indomethacin alone. There was, however, no significant difference in Ccr and FNa between the groups. These data indicate that dopamine overcomes indomethacins renal side effects of tubular origin, but it cannot prevent the renal vasoconstrictive action of vasoconstrictor hormones following the inhibition of prostaglandin synthesis by indomethacin. Considering that RBF and GFR turn to normal approximately 12 hours after the last dose of indomethacin, and that with the use of dopamine systemic blood pressure and peripheral circulation can also be normalized and to some extent myocardiac contractility improved, low doses of dopamine can be used instead of furosemide in the sick preterm infant with PDA when indomethacin therapy is indicated.

Cardiovascular response to dopamine in hypotensive preterm neonates with severe hyaline membrane disease.

The effect of low dose (2, 4, and 8 micrograms/kg per min) dopamine infusion on blood pressure, heart rate and renal function was studied in 18 hypotensive, preterm infants with severe hyaline membrane disease (HMD). Significant dose-related effects found during dopamine infusion were systolic and diastolic blood pressure elevation and diuretic effect, while heart rate increase occurred only with 8 micrograms/kg per min of the drug. This indicates, that in the preterm neonate, dopamine at low doses has a pronounced effect on the alpha- and dopamine-receptors, while its beta-receptor stimulating activity is minimal. We demonstrated a significantly decreased metabolic clearance rate of dopamine in preterm infants. Thus, beside the differences in the vascular receptors' maturation, the decreased metabolic clearance rate should also be taken into account when explaining the cardiovascular and renal effects of low dose dopamine infusion in these babies. Dopamine was found to be useful in normalizing low arterial blood pressure, in improving impaired peripheral circulation, and in producing a marked diuresis in hypotensive preterm neonates with severe hyaline membrane disease.

The clinical importance of urinary tract infections during pregnancy. III. Neonatal morbidity and mortality.

The third part of the series shows that the various forms of maternal urinary tract infections have a negative effect on the newborn. Already at birth, there are several depressed babies in need of resuscitation. The frequency of prolonged jaundice requiring treatment has been increasing. The babies are more predisposed to infections. Congenital pneumonia more often occurs. As a result, the exposure of babies to drugs and x-rays is greater and perinatal mortality is higher. The newborn are much frailer than they should be on the basis of the frequency of their prematurity. The epidemiological analysis raises the possibility of the harmful effect of intrauterine infections in bacteriuric and pyelonephritic pregnancies.

[Tolazoline and dopamine in the treatment of the persistent fetal circulation syndrome]. / Tolazoline und Dopamin bei der Behandlung des persistierenden fetalen Zirkulationssyndroms.

The combined application of Tolazoline and Dopamine for the treatment of the persistent fetal circulation syndrome showed that Dopamine prevented the most common side effects of Tolazoline i.e. systemic hypotension and oliguria. The authors emphasize the importance of continuous monitoring of the systemic blood pressure in infants during this treatment.

Effects of dopamine on renal functions in premature neonates with respiratory distress syndrome.

The renal effects of dopamine have been studied in preterm infants with RDS. Dopamine has been given in doses of 0.5-2.0 microgram/kg/min as a continuous intravenous infusion in cases of peripheral circulatory disturbances. As a result, the circulation became stable and some renal parameters improved. There was a + 106% increase of urine output as well as a + 73%, + 140%, + 21% increase in Na-excretion, FeNa, creatinine clearance respectively. In accordance with the marked increase in phosphorus excretion the titratable acidity was also increased. There was a significant decrease in the renal urea excretion and free water clearance. These alterations were probably caused by an intrarenal hemodynamic redistribution. The possible mechanism of the renal changes are also discussed. The observations demonstrate the functional maturity of renal dopaminergic receptors in the preterm infants.

Effects of continuous positive airway pressure on renal function in prematures.

The effects of continuous positive airway pressure respiratory therapy--used in centrencephalic apnea in premature infants--has been investigated at a value of +6 cm H2O end-expiratory pressure. The results showed a significantly decreased glomerular filtration rate, decreased sodium and hydrogen ion excretion and urine output, without changes in systemic blood pressure, pulse rate, and blood gas values. At +3 cm H2O end-expiratory pressure no changes were observed.