Several drugs used in the first trimester of pregnancy are transported by P-glycoprotein (P-gp), an efflux transporter expressed in the placenta. |
Some of these drugs were shown to have associations with specific types of anomalies. Drug interactions mediated by P-gp increase the risk of specific anomalies of these drugs compared with their use alone. |
The pattern of risk increment following drug interactions suggests the role of P-gp in limiting fetal drug exposure. |
1 Introduction
2 Methods
2.1 Case Selection
2.2 Reference Population Sampling
2.3 Exposure Variable
Characteristics |
N
| % |
---|---|---|
Sex | ||
Boy | 2617 | 56.5 |
Girl | 2011 | 43.4 |
Missing | 6 | 0.1 |
Type of birth | ||
Live birth | 4361 | 94.1 |
Termination of pregnancy | 184 | 4.0 |
Stillbirth | 58 | 1.3 |
Miscarriage (>24 weeks) | 31 | 0.7 |
Types of anomaliesa
| ||
Heart | 1244 | 26.8 |
Musculoskeletal | 1054 | 22.7 |
Digestive system | 594 | 12.8 |
Urinary | 507 | 10.9 |
Orofacial clefts | 436 | 9.4 |
Genital | 406 | 8.8 |
Nervous system | 347 | 7.5 |
Limb | 342 | 7.4 |
Eye, ear, face and neck | 152 | 3.3 |
Respiratory | 84 | 1.8 |
2.4 Statistical Analysis
3 Results
3.1 User Rates of Drugs Associated with P-Glycoprotein (P-gp) During Pregnancy
Drug/drug classes | Types of specific anomalies | Number of case users (%) |
p value | Number of users in reference population [N = 25,126] (%) | OR (95 % CI) |
p value | |
---|---|---|---|---|---|---|---|
Within specific anomalies | Within all other anomalies [N = 4634 − n
s] | ||||||
H2-receptor antagonist (cimetidine, ranitidine) | Heart (n
s = 244) | 5 (0.4) | 3 (0.1) | 0.037a
| 161 (0.64) | 0.63 (0.26–1.53) | 0.3 |
Proton pump inhibitors (omeprazole, pantoprazole) | Genital (n
s = 406) | 9 (2. 2) | 52 (1.2) | 0.046 | 327 (1.3) | 1.72 (0.88–3.36) | 0.11 |
Morphine | Respiratory (n
s = 84) | 1 (1.2) | 7 (0.2) | 0.018a
| 3 (0.01) | 100.9 (10.39–979.94) | 0.13a
|
Antipsychotics (haloperidol, quetiapine, risperidone) | Musculoskeletal (n
s = 1054) | 5 (0.5) | 3 (0.1) | 0.018a
| 57 (0.23) | 2.1 (0.84–5.24) | 0.1 |
SSRIs (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine) | Nervous system (n
s = 347) | 11 (3.2) | 74 (1.7) | 0.054b
| 576 (2.3) | 1.4 (0.76–2.56) | 0.28 |