FUNCTION OF CARNITINE IN METABOLISM OF PR EGNANT-WOMEN AND OF FETUSESIN THE PRENATAL AND PERINATAL-PERIOD - ANIMAL AND CLINICAL-STUDIES

Carnitine was discovered at the beginning of this century, but was nea rly forgotten until its importance in fatty acid metabolism was establ ished 50 years later. In the past years, several other functions of ca rnitine in cellular metabolism have been described. The lung contains more than 40 different cell types, most of them involved in lipid meta bolism. Pulmonary surfactant, a complex of 90% lipids and 10% lung spe cific apoproteins, is synthesized and secreated from type II cells. Su rfactant is present as a monolayer at the air-liquid interface in the alveoli and decreases surface tension. Dipalmitoyl phosphatidylcholine (DPPC) is functionally and quantitatively the most important constitu ent of the surfactant complex. A deficiency in fetal lung surfactant i s the primary cause of the respiratory distress syndrome (RDS), the mo st severe complication of preterm infants. Glucocorticoids are frequen tly used to accelerate fetal pulmonary maturation. However, a consider able number of infants fail to respond to this therapy. Maternal admin istration of L-carnitine significantly increased the DPPC content of f etal rat lungs. The effect of maternal treatment with a carnitine beta methasone combination was synergistic, especially with lower betametha sone doses. Consequently the minimal dose of betamethasone which affec ts the DPPC content and accelerate the morphological maturation of the fetal lung was determined. This minimal dose in combination with L-ca rnitine increased the DPPC content on day 19 of gestation to levels fo und on the 20th gestational day which allows the survival of most of t he preterm rats (term 22 days). Results of clinical trials show that a ntenatal treatment with a low dose betamethasone-L-camitine combinatio n has a clear advantage over standard betamethasone therapy. A multice nter study is in progress. Plasma carnitine levels at delivery are dec reased to about half of the concentrations seen in non-pregnant women. Similar low levels are found only in patients with carnitine deficien cy. Already in the 12th week of gestation the mean whole blood and pla sma carnitine levels were found to be significantly lower than those o f controls. The reason for increased excretion of acylcarnitines durin g pregnancy is not known, but could be a detoxifying function similar to that found in patients with inborn errors of fatty acid metabolism and organic acidurias Carnitine substitution (1 g daily) from the 20th gestational week up to parturition resulted in an increase of free ca rnitine levels in maternal plasma. A dosage of 0.5 g/day was without e ffect. Prolonged substitution in pregnant women, especially in risk pr egnancies may be preferable to high doses of carnitine administered sh ortly before imminent premature delivery.