Interest of the trajectory method for the evaluation of outcomes after in utero drug exposure: example of anxiolytics and hypnotics.
OBJECTIVE
The aim of this study was to examine the potential benefit to take into account duration and intensity of drug exposure using the recently published method based on individual drug trajectories. This approach was used to define profiles of exposure to anxiolytics/hypnotics during pregnancy and to evaluate the potential effect on newborn health.


METHODS
The study was performed in EFEMERIS database (54 918 mother-children pairs). An estimation of adaptation to extrauterine life was assessed using several criteria especially cardio-respiratory symptoms. A proxy variable called "neonatal pathology" was created. The occurrence of this event was studied using two approaches: The Standard Method comparing exposed and unexposed newborns, The Trajectory Method comparing the different profiles of exposure.


RESULTS
Around 5% of newborns (n = 2768) were identified to be exposed to anxiolytics or hypnotics during pregnancy. Using the Standard Method, 6.2% of exposed newborns developed a "neonatal pathology" against 4.8% of unexposed newborns (odds ratios [OR] = 0.9[0.8-1.2], p = 0.7). With the Trajectory Method taking into account evolution of exposure during pregnancy and treatment intensity, four profiles of pregnant women were identified. A significant difference in the rates of "neonatal pathologies" was observed between profiles (p = 0.0002). Newborns of the two profiles exposed in utero to high constant level of anxiolytics or hypnotics were more at risk of developing "neonatal pathology" than unexposed newborns (OR1= 2.0 [1.0-3.9] and OR2= 7.6 [2.8-20.5]).


CONCLUSIONS
The present study demonstrates the interest of this method based on individual drug trajectories for the evaluation of outcomes in pharmaco-epidemiological studies and more specifically during pregnancy. Copyright © 2017 John Wiley & Sons, Ltd.
Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire, Faculté de Médecine, Université Toulouse III, Toulouse, France.
Caroline
http://orcid.org/0000-0001-7651-9130
C
Hurault-Delarue
Institut de Mathématiques de Toulouse, Laboratoire de Statistique et Probabilités, CNRS (UMR 5219), Paul Sabatier Université, Toulouse, France.
Cécile
C
Chouquet
Institut de Mathématiques de Toulouse, Laboratoire de Statistique et Probabilités, CNRS (UMR 5219), Paul Sabatier Université, Toulouse, France.
Nicolas
N
Savy
Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire, Faculté de Médecine, Université Toulouse III, Toulouse, France.
Isabelle
I
Lacroix
Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire, Faculté de Médecine, Université Toulouse III, Toulouse, France.
Anna-Belle
AB
Beau
Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire, Faculté de Médecine, Université Toulouse III, Toulouse, France.
Jean-Louis
JL
Montastruc
Pharmacologie Médicale et Clinique, UMR INSERM 1027, Centre Hospitalier Universitaire, Faculté de Médecine, Université Toulouse III, Toulouse, France.
Christine
C
Damase-Michel
D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000453:epidemiology; D008297:Male; D017891:Pharmacoepidemiology / Q000379:methods; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*
D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives
adaptation to extrauterine life; anxiolytic drugs; drug trajectories; hypnotic drugs; pregnancy