The therapeutic effect of betamethasone for prenatal lung maturation in very low birthweight infants may be influenced by maternal and fetal ABCB1-polymorphism – A pilot study

Ziel: A retrospective pilot study was performed as a preparation for a prospective one planed to prove the hypothesis addressed in the title.

Methodik: In a cohort of 183 preterm infants consecutively delivered before 28 weeks gestation in our perinatal center level I we identified 10 infants from 8 mothers who fulfilled the following criteria: caucasian, eutroph, betamethasone treatment for lung maturation completed, intrauterine infection excluded by blood analyses and placenta histology, fluids clear, no malformation or severe disease or complication. Infants fulfilling criteria for the diagnosis of surfactant deficiency syndrom were classified as non-responders. Infants not needing artifical ventilation on the first day were defined as responders. After informed consent ABCB1 genotype (exon 21, 2677G/T/A and exon 26, 3435C/T) was assessed in mothers and children.

Ergebnis: Nonresponders: three singletons showed the wild type GG/CC known for high P-glycoprotein (P-gp) expression implying low penetration of betamethasone to the fetus. Two mothers showed GG/CC, too. Responders: neither children nor mothers showed the wild type. Two children and one mother were homozygous TT on exon 26. This genotype is known for low P-gp expression implying high bioavailability of betamethasone in the fetus.

Schlussfolgerung: Variability in the gene encoding the ABCB1-transporter in the placenta may influence the fetal bioavailability of betamethasone for prenatal lung maturation. To improve the number of responders to fetal lung maturation therapy the influence of pharmacogenetics on pharmacokinetics at the blood-placenta barrier should be examined.

Literatur: Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmöller J, Johne A, Cascobi I, Gerloff T, Roots I, Eichelbaum M. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlations of one allele with P-glycoprotein expression and activity in vivo. Proc Nati Acad Sci USA. 2000; 97:3473-8. Ceckova-Novotna M, Pavek P, Staud F. P-glycoprotein in the placenta:expression, localization, regulation and fuction. Reproductive Toxicology. 2006; 22:400-10. Vähäkangas K, Myllynen P. Drug transporters in the human blood-placenta barrier. Britisch Journal of Pharmacology. 2009; 158:665-78.