Some medicines are known to cause abnormal fetal development resulting in fetal death or babies born with birth defects. Some of these effects may happen very early in pregnancy, within the first 6 weeks of gestation, before most patients realise they are pregnant. It is therefore important that women who are in their reproductive age and are prescribed any teratogenic medicine should be made aware of the risk and placed on reliable contraception. Some medicines can cause fetal damage in the second or third trimester.
Where possible, stop teratogenic medicines before a pregnancy is planned and prescribe suitable alternatives.
Any medicine that is prescribed during pregnancy must be carefully evaluated, and risk versus benefit should be assessed before use. Refer to prescriber information for details regarding risks in pregnancy. .
Refer pregnancies exposed to teratogenic medicines during the first trimester for a detailed fetal anomaly scan.
The table below lists some commonly used medicines that are associated with birth defects.
| MEDICINES | ADVERSE FETAL EFFECTS | LoE |
| Androgens | Masculinisation of the developing female fetus can occur. | III [1] |
| ACE- inhibitors/ ARBs | Fetal hypotension resulting in fetal kidney hypoperfusion and anuria, with fetal growth restriction and demise. | III [2] |
| Anticonvulsants: | ||
| Carbamazepine | Increases the risk of facial dysmorphology, neural tube defects, cardiovascular defects, and urinary tract defects. | II [3] |
| Phenytoin | Increases the risk of fetal hydantoin syndrome, consisting of facial dysmorphology, cleft palate, ventricular septal defect, and growth and intellectual disability. | II [3] |
| Valproic acid |
Increases the risk of spina bifida, facial dysmorphology, autism, atrial septal defect, cleft palate, hypospadias, polydactyly, craniosynostosis, limb abnormalities, neurodevelopmental problems (approximately 40%) and autism[4]. |
II [3] |
| Antidepressants | SSRIs should in general be continued during pregnancy and breastfeeding. There is uncertainty in the evidence, but potential complications may include an increased risk of birth defects, postpartum haemorrhage, premature birth and low birth weight. | III [5] |
| Carbimazole | Increased risk of birth defects in the first trimester and at high daily doses of ≥15 mg. | III [6] |
| Dolutegravir | There is an increased risk of neural tube birth defects involving the brain, spine, and spinal cord; if used within the first 6 weeks of pregnancy. | III [7] |
| Efavirenz | No increased prevalence of birth defects detected and in a large multi-cohort analysis or from a South African exposure registry. | I [8] |
| Lithium | First trimester exposure is associated with an increased risk of birth defects. | II [9] |
| Macrolide | In a large population-based cohort study, when compared to penicillin, first trimester macrolide exposure was associated with increased risk of cardiovascular malformations, and macrolide exposure in any trimester was associated with increased risk of genital malformations. The majority of macrolide exposures in this study (93%) were to erythromycin, but a class effect cannot be ruled out. Macrolides should only be prescribed in pregnancy when clearly indicated. | III [10] |
| Methotrexate | Pregnancy loss, growth restriction, microcephaly, intellectual disability. | III [11] |
| Contraceptive agents and sex steroids (progestin) | There is no risk for congenital defects if contraceptive agents were used inadvertently during the first trimester. Very high doses of androgen hormone-derived progestin may produce masculinisation if used before 13 weeks of pregnancy. | II [12] |
| Prednisone | Prednisone does not represent a major teratogenic risk in humans at therapeutic doses, but there is an increased risk (about 3-fold) for cleft palate. | II [13] |
| Retinoids | Oral formulation is associated with increased risk of CNS, cardioaortic, ear, and clefting defects. Topical administration is very unlikely to have teratogenic potential because teratogenic serum levels cannot be attained by topical exposure to retinoids. | III [14] |
| Tetracyclines (e.g. docycycline) | Produces bone and teeth staining; it does not increase the risk of any malformations but should not be used during pregnancy. | III [15] |
| Warfarin | Early exposure during pregnancy can result in nasal hypoplasia, intrauterine growth restriction and miscarriage. CNS malformations can occur in late pregnancy exposure because of bleeding. In women with new generation prosthetic heart valves taking warfarin daily at a dose of ≤5mg, the risk of serious teratogenesis is small and warfarin may be safely continued in the first trimester being discontinued prior to delivery to avoid intracranial bleeding in the newborn (substituted with heparin). | II [16] |
LoEIII [6]
LoEIII [7]
LoEI [8]
LoEII [9]
ACE-inhibitor: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; LoE: level of evidence; DS-TB: drug-sensitive tuberculosis; RHZE: rifampicin/isoniazid/pyrazinamide/ethambutol; CNS: central nervous system