Drugs | Critical Period | Risk magnitude | Developmental Toxicity |
Anticonvulsants
1st gen: CBZ, PHB, PHT, Primidone, VPA
2nd gen: Lamotrigenes | 1st trimester
3rd trimester | | Structural defects
Hemorrhagic disease |
Anti-infectives | Kanamycin,
Streptomycin (throughout pregnancy),
Fluconazole >400mg/d (1st trimester),
Quinine @toxic doses (1st trimester),
Tetracycline (>4mos) | | |
Anti-neoplastics | Busulfan (1st trimester),
Cyclophosphamide (1st trimester),
MTX >10mg/wk (6-8wks),
Tamoxifen | | |
Corticosteroids | < 10 weeks
Throughout pregnancy | Oral clefts [2-7x risk]
Growth restriction [if
prolonged therapy] | Cleft lip + palate
Growth restriction (300-400g) |
B1-Blockers | 2nd - 3rd trimester | Dose and duration dep | ↓ placental weight, birth weight. IUGR.
d/t decreased fetal perfusion |
Diethylstilbestrol | 10-18 week
up to 20 weeks | Vaginal adenocarcinoma
Genital defects | Female and male genital defects, infertility,
preterm birth, ectopic pregnancy, ↑SABs |
Iodine | 2nd - 3rd trimester | Dose and duration dep | Hypothyroidism, goiter |
Lithium | 1st trimester
3rd trimester | cardiac defects
newborn toxicity | Various heart defects
Ebstein's anomaly (downward displacement
of triscuspid valve to right ventricle)
Toxic effects: cyanosis, hypotonia, bradycardia, atrial flutter, Twave
inversion, cardiomegaly, GI bleed, sz, diabetes insipudius,
shock, hepatom |
Methylene blue | 2nd - 3rd trimester | 20% jejunal-ileal astresias | Fetus: jejunal-ileal astresias --> death
Newborn: hyperbilil, hemolytic anemia,
methemoglobinemia |
Methimazole
Carbimazole | Up to 9 weeks after LMP | Low | Pattern of rare defects --> Scalp or patchy hair defects, choanal atresia, esophageal
atresia w/ fistula, minor facial anomalies, hypoplast/absent
nipples, hypothyroidism, goiter |
Misoprostol | 1st trimester (esp 6-8wk) | 7x for Mobius syndrome | Abortion, Mobius syndrome, defects of
cranium/scalp, oral cleft, etc
Mobius: 6th and 7th nerve palsies |
Mycophenolate | 1st trimester | SAB (spont.abortion)- 45%
Defects -22% | Defcts of external ear, face, oral clefts,
heart, kidney, esophagus, distal limbs |
NSAID | 1st trimester
> 32 weeks | SAB, ASD/VSD
Patent ductus Arteriosus,
renal toxicity | SAB, cardiac tox, renal tox
Premature closure DA - reversible
Patent DA - irreversible |
Penicillamine | Unknown | <5% | Cutis laxa |
SSRI's | 1st trimester
>20 weeks | --> SAB/PPHN: 2-6%
--> neonatal withdrawal: 30% | Birth defects, SAB
Withdrawl, PPHN (persistent
HTN of newborn)
Cardiac toxicity, SAB, carniosynostosis, omphalocele,
anencephaly, gastroschisis, low birth weight, PPHN,
neurobehavior defcts |
Trimethoprim | 1st trimester | Unknown | Cardiovascular
Can also cause oral cleft, urinary tract, and neural tube defect |
Thalidomide | 35-40 days after 1st day
of LMP [50-100mg/d] | 20-30% | Defects of limbs, skeletal defects,
craniofacial, CNS, major organs |
Vitamin A (Acitretin-
Etretinate, Accutane) | 15 days after conception
to end of 1st trimester | 30-50% | SAB, CNS, craniocial, cardiovascular, thymus
gland, miscellaneous |
Warfarin | 6th - 9th week
- throughout | --> fetal warfarin syndrome 5-10%
--> CNS defects 4-5% | Fetal warfarin syndrome, CNS, optic, cardiac, IUGR
(warfarin has very long half life) |
Alcohol | Throughout | NO SAFE DOSE!!!
Can cause fetal alcohol
syndrome, disruption of NTs
(Glutamate, GABA) | IUGR + MR + Facial anomalies=classical triad
Microcephaly, long term neurobehavioral
abnormalities |
Cigarette smoking | 1st trimester
2nd - 3rd trimester | -> Malformations, SAB
-> growth | Cleft lip, club foot, cardiac defects,
carniosynostosis, Poland syndrome,
transverse limb reduction |
Toluene | Unknown | Unknown | Similar to FAS |
Cocaine | Unknown | Unknown | Causes vascular disruption -- SAB, stillbirths,
IUGR, preterm delivery, etc |
ACE-I, ARBs | 2nd - 3rd trimester | Dose / duration dependent | Renal failure, IUGR, hypocalvaria, hypotension |
Androgenic hormones | 8-13th week
2nd - 3rd trimester | Unknown | Masculinization of female fetus
(labial fusion, and clitoral hypertrophy) |