J.D. Brunt

Plasma prostaglandin levels during early neonatal life following term and pre-term delivery.

The concentrations of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-oxo-PGF (PGFM) have been measured by sensitive and specific radioimmunoassays in neonatal plasma after term and pre-term delivery. Blood samples were taken in the term delivery group from the umbilical artery at birth and on the sixth post-natal day and after pre-term delivery at 2-4 days, on the sixth day, at 2-4 weeks and at 5-8 weeks after birth. The levels of prostaglandins circulating during the first month of life were far greater than those found in normal adults. In neonates delivered at term the plasma concentration of PGE was significantly lower six days after delivery compared with the concentration at delivery whereas the concentrations of PGF and PGFM were essentially unchanged. Following pre-term delivery prostaglandin concentrations declined with increasing neonatal age although only levels of PGE at 5-8 weeks of age were within the normal range of adult values. Comparison of prostaglandin levels six days after delivery between neonates born at term and pre-term showed no significant differences. These results suggest that prematurity per se is not associated with marked abnormalities in the ability of the neonate to synthesize or metabolize prostaglandins.

Oral prostaglandin E2 in ductus-dependent pulmonary circulation.

Prostaglandin E2 (PGE2) was administered orally, in doses of 12–65, ug/kg at intervals of 1–4 hours, to 12 neonates in whom the pulmonary circulation depended on patency of the ductus arteriosus. After an oral dose, both oxygen saturation (Sao2) and plasma PGE2 concentration increased consistently within 15–30 minutes, reaching values comparable to those during i.v. infusions. Treatment continued for 5 days to 4 months. In eight infants, PGE2 withdrawal resulted in a decrease of Sao2, from a mean of 75 ± 7% to 57 + 10% (± SD).The ductus remained responsive for long periods –- in four infants, for over 3 months. Consequently, surgery could be delayed until the infants and their pulmonary arteries had grown. Side effects during oral therapy were similar to those during i.v. infusion but were less severe in this series. The effectiveness and simplicity of oral PGE2 administration have advantages over i.v. administration, especially for long-term treatment.

PROSTAGLANDINS IN THE HUMAN UMBILICAL CIRCULATION AT BIRTH

Prostaglandin E (PGE), prostaglandin F (PGF) and 13, 14‐dihydro‐15‐keto‐prostaglandin F (PGFM) have been measured in umbilical cord plasma obtained immediately after delivery of the baby before clamping of the cord. In general the prostaglandin levels followed the pattern PGFM>PGE>PGF. A significant arterio‐venous difference was demonstrated only for PGE with raised venous levels (P<0.01). In cord blood samples obtained from infants whose mothers had received epidural anaesthesia, no arterio‐venous difference for PGE could be demonstrated although the mean levels were not significantly different from controls. The concentrations of prostaglandins in Umbilical cord plasma proximal to the placenta were found to rise continuously from the time of delivery of the baby with no significant changes after cord clamping or placental delivery. The possible physiological significance of these findings is discussed.

CONCENTRATIONS OF THE PROSTACYCLIN METABOLITE, 6–KETO–PROSTAGLANDIN F1α, IN AMNIOTIC FLUID DURING LATE PREGNANCY AND LABOUR.

Concentrations of 6–keto–prostaglandin F1α (6–keto–PGF1α, the stable metabolite of prostacyclin, PGI2) have been measured in amniotic fluid obtained during late pregnancy and labour. Samples taken at amniotomy during spontaneous labour contained a significantly greater concentration of 6–keto–PGF1α than samples taken at amniotomy before the onset of labour (p <0.01). There was no correlation between the level of 6–keto–PGF1α, in amniotic fluid before labour and gestational age (p > 0 1). It is suggested that prostacyclin may have a functional role in the mechanism of parturition in man.

PROSTAGLANDINS IN UMBILICAL PLASMA AT ELECTIVE CAESAREAN SECTION

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14‐dihydro‐l5‐keto‐prostaglandin F (PGFM) have been measured in umbilical cord plasma obtained immediately after delivery by elective Caesarean section. Umbilical venous plasma levels of PGE were significantly greater than the corresponding arterial levels (p <0.02); there were no significant arterio‐venous differences for PGF or PGFM. In general, concentrations of PGFM exceeded those of PGE which in turn were greater than concentrations of PGF. Umbilical venous levels of PGE and both arterial and venous levels of PGF and PGFM were significantly greater after spontaneous labour with vaginal delivery than after elective Caesarean section.

The effect of cervical encerclage on plasma prostaglandin concentrations during early human pregnancy.

In women having either cervical encerclage under general anaesthesia or a vaginal examination in the early second trimester of pregnancy, peripheral plasma levels of 13,14‐dihydro‐l5‐keto prostaglandin F (PGFM) were measured before and after each procedure. A significant rise in circulating levels of PGFM was found within minutes of completing cervical encerclage but not after vaginal examination or induction of general anaesthesia.

Selective elevation of circulating prostaglandin concentrations in hyaline membrane disease in pre-term infants

The plasma concentrations of prostaglandins E and F (PGE, PGF) and 13, 14-dihydro-15-keto-PGF (PGFM) have been measured in pre-term neonates with hyaline membrane disease (HMD) and controls. The concentrations of PGF and PGFM were significantly higher in infants having HMD with a disproportionate increase in PGFM levels for the increase in PGF found. The vasoconstrictor nature of PGF may contribute to the morbidity associated with HMD and the possible therapeutic benefit from the use of prostaglandin synthetase inhibitors is discussed.