Frequency of differential placental transfer to twins of maternal antiretroviral medications.


Journal

European journal of obstetrics, gynecology, and reproductive biology
ISSN: 1872-7654
Titre abrégé: Eur J Obstet Gynecol Reprod Biol
Pays: Ireland
ID NLM: 0375672

Informations de publication

Date de publication:
Jan 2021
Historique:
received: 09 08 2020
revised: 01 11 2020
accepted: 05 11 2020
pubmed: 8 12 2020
medline: 15 5 2021
entrez: 7 12 2020
Statut: ppublish

Résumé

Placental passage of drugs in twins is poorly understood, and is unknown regarding antiretrovirals (ARVs). In the event of large differences in the exposure of 2 twins to the same maternal therapy, this could have a clinical impact in terms of prevention of perinatal HIV transmission or adverse effects. To describe the frequency of differential transplacental passage of antiretrovirals between twins. The study was performed retrospectively, on data from women included in a multicenter perinatal HIV cohort study. All twin pairs for which the mother received antiretroviral therapy and for which drug concentrations in both of the umbilical cords after cord clamping at delivery were studied. We considered that a difference in concentrations of more than 50 % between twins was a substantial difference (ratios below 0.67 or above 1.50). We analyzed 29 twin pairs, 27 dichorionic and 2 monochorionic diamniotic. Cord blood concentrations differed between the 2 twins by more than 50 % for at least one ARV in 9 twin pairs, 8 dichorionic and 1 monochorionic. Discordant concentrations were observed in one or more cases for several nucleoside reverse transcriptase inhibitors (tenofovir, emtricitabine, lamivudine, zidovudine) and protease inhibitors (atazanavir, lopinavir, saquinavir et ritonavir); within individual twin pairs placental transfer was discordant for one or more ARVs, but identical for others. Concentrations differed in nearly one third of twin pairs. This may be due to interindividual genetic variability of placental transporters between dizygotic twins as well as physiological differences between twins.

Sections du résumé

BACKGROUND BACKGROUND
Placental passage of drugs in twins is poorly understood, and is unknown regarding antiretrovirals (ARVs). In the event of large differences in the exposure of 2 twins to the same maternal therapy, this could have a clinical impact in terms of prevention of perinatal HIV transmission or adverse effects.
OBJECTIVE OBJECTIVE
To describe the frequency of differential transplacental passage of antiretrovirals between twins.
STUDY DESIGN METHODS
The study was performed retrospectively, on data from women included in a multicenter perinatal HIV cohort study. All twin pairs for which the mother received antiretroviral therapy and for which drug concentrations in both of the umbilical cords after cord clamping at delivery were studied. We considered that a difference in concentrations of more than 50 % between twins was a substantial difference (ratios below 0.67 or above 1.50).
RESULTS RESULTS
We analyzed 29 twin pairs, 27 dichorionic and 2 monochorionic diamniotic. Cord blood concentrations differed between the 2 twins by more than 50 % for at least one ARV in 9 twin pairs, 8 dichorionic and 1 monochorionic. Discordant concentrations were observed in one or more cases for several nucleoside reverse transcriptase inhibitors (tenofovir, emtricitabine, lamivudine, zidovudine) and protease inhibitors (atazanavir, lopinavir, saquinavir et ritonavir); within individual twin pairs placental transfer was discordant for one or more ARVs, but identical for others.
CONCLUSION CONCLUSIONS
Concentrations differed in nearly one third of twin pairs. This may be due to interindividual genetic variability of placental transporters between dizygotic twins as well as physiological differences between twins.

Identifiants

pubmed: 33285497
pii: S0301-2115(20)30715-6
doi: 10.1016/j.ejogrb.2020.11.004
pii:
doi:

Substances chimiques

Pharmaceutical Preparations 0

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

405-411

Informations de copyright

Copyright © 2020. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors report no declarations of interest.

Auteurs

Margaux Louchet (M)

Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Gynécologie-Obstétrique, Colombes, France; Université de Paris, Paris, France; FHU PREMA, Paris, France.

Gilles Peytavin (G)

Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Pharmacologie-Toxicologie, HUPNVS, Paris, France; Inserm IAME U1137, F-75018, Paris, France.

Hélène Didelot (H)

Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Gynécologie-Obstétrique, Colombes, France; Université de Paris, Paris, France.

Minh Lê (M)

Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Pharmacologie-Toxicologie, HUPNVS, Paris, France.

Agnès Bourgeois-Moine (A)

FHU PREMA, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Gynécologie-Obstétrique, HUPNVS, Paris, France.

Lionel Carbillon (L)

Assistance Publique-Hôpitaux de Paris, Hôpital Jean Verdier, Service de Gynécologie-Obstétrique, Bondy, France.

Dominique Luton (D)

Université de Paris, Paris, France; FHU PREMA, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Gynécologie-Obstétrique, HUPNVS, Paris, France.

Isabelle Matheron (I)

Centre Hospitalier Intercommunal Villeneuve-St-George, Service de Gynécologie-Obstétrique, Villeneuve St George, France.

Luc Rigonnot (L)

Centre Hospitalier Sud Francilien, Service de Gynécologie-Obstétrique, Corbeil-Essonnes, France.

Laurent Mandelbrot (L)

Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Gynécologie-Obstétrique, Colombes, France; Université de Paris, Paris, France; FHU PREMA, Paris, France; Inserm IAME U1137, F-75018, Paris, France. Electronic address: laurent.mandelbrot@aphp.fr.

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