Nitric oxide donors in pregnancy: fetomaternal hemodynamic effects induced in mild pre-eclampsia and threatened preterm labor.

OBJECTIVE: The present study was performed to determine whether there are significant differences in the effects of the nitric oxide donor, glyceryl trinitrate, administration in pregnancies complicated by mild pre-eclampsia compared to the effects in pregnancies which are uncomplicated by this pathology. Glyceryl trinitrate is able to release nitric oxide (NO); deficiency of NO has been hypothesized in the pathogenesis of pre-eclamptic disorders. METHODS: In this prospective study, ten patients with threatened preterm labor and ten patients with mild preeclampsia were studied at around 30 weeks of pregnancy. The maternal blood pressure, maternal heart rate, fetal heart rate and flow velocity waveforms of the placental uterine artery, umbilical artery and fetal middle cerebral artery, evaluated by means of color Doppler and pulsed Doppler, were recorded before and 10, 20 and 30 min after the sublingual administration of 0.3 mg of glyceryl trinitrate or placebo. The pulsatility index (PI) was calculated. The percentage change from the control period (delta %) was calculated for each parameter at 10, 20 and 30 min. Ten normal pregnant women at the same gestational age were used as controls and were administered a placebo. RESULTS: The maternal blood pressure recorded as systolic and diastolic values, demonstrated a significant decrease in the pre-eclampsia group after glyceryl trinitrate administration; the delta % at any time considered was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the placental uterine artery showed a significant decrease in both groups after 20 and 30 min from drug administration; the delta % at 20 and 30 min was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the umbilical artery showed a significant decrease after 30 min from the glyceryl trinitrate administration. The fetal heart rate showed no significant variations during the study in either group. The PI of the fetal middle cerebral artery showed no significant variations during the study in either group. No parameter was changed in the control group. CONCLUSION: Glyceryl trinitrate administration was followed by a greater reduction of the resistance to blood flow in the fetoplacental circulation of the pregnancies affected by mild pre-eclampsia compared to pregnancies uncomplicated by this pathology. This effect can be attributed to the NO released by the drug which offsets the decreased production of NO, postulated to contribute to the pathogenesis of pre-eclampsia.

[Functional aspects of the fetal urinary apparatus in relation to growth]. / Aspetti funzionali dell'apparato urinario fetale in rapporto all' accrescimento.

The normal and regular development of the fetal renal function is related to fetal growth and to the correct development of the fetal lung. Besides, the fetal kidneys plays an important role in the regulation of the hydro-electrolytic balance and in the modulation of the fetal arterial pressure. The postnatal renal failure is one of the most dangerous factors which may occur in the very small preterm babies (birth weight below 1000 g) and their therapeutical answer depends on the degree of kidney maturation. The knowledge of the kidney maturation process is one of the actual controversies in perinatal medicine. The development of the renal nephron and of the excretory system continues until 32-36 weeks of gestation, their maturation process ends only some months after birth. At 9 weeks of gestation the embryonic kidney may be seen in a transvaginal ultrasonographic scanning; the calico-pelvic system is visible from the 11th week of gestation and the bladder may be seen by ultrasound from the 12 weeks' gestation. The fetal glomerular ultrafiltration process starts at the 10-11 week of gestation and the most important factors that improve the volume of glomerular ultrafiltrate is the total renal mass which is related to the number of functional nephron units. The Doppler velocimetry performed on the fetal renal artery has shown that the fetal renal blood flow increases with the increase of the renal volume and gestational age and it depends on the cardiac output. In the renal artery the resistance to blood flow decreases with gestational age. During fetal hypoxia there is a reduction of the amniotic fluid production; this phenomenon is related to the redistribution of the fetal blood flow with a decrease of the perfusion of peripheric organs (as the kidney) and an increase of the perfusion of brain, heart, liver and adrenals. The hypoxic fetal kidney is ischemic; moreover, the urine production rate is diminished and the humoral response of the kidney increase the fetal arterial pressure which maintains the haemodynamic compensation to hypoxia. When this situation is prolonged, there is possibly renal failure. The fetal renal ultrasonographic examination can give important information about the maturity degree of the fetal kidney and the evaluation of Doppler velocimetry on renal artery and the evaluation of the amniotic fluid allow the monitoring of fetal hypoxia. In future the Doppler velocimetry of intrarenal arteries and the biochemical evaluation of the amniotic fluid may a real evaluation of the fetal renal function.