Alcohol | | Fetal alcohol syndrome: IUGR, maxillary hypoplasia, reduction in width of palpebral fissure, microcephaly, mental retardation | High for alcohol consumption of 6 oz or more per day; lower exposures also can induce detrimental effects |
Amphetamines | | Congenital heart disease, IUGR | |
Analgesics and antipyretic drugs | Aspirin | Prolonged gestation; increased risk of maternal and fetal hemorrhage | |
| Acetaminophen | Maternal and fetal renal toxicity with chronic ingestion of high doses | |
| Nonsteroid antiinflammatory drugs | Constriction of the ductus arteriosus | |
Analgesics (narcotics) | Codeine | Respiratory system malformations | Risk not clearly defined because of confounders such as lifestyle and use of multiple drugs; risk of medical use appears to carry little, if any, fetal risk |
Androgens | | Masculinization of the female embryo, clitoromegaly with or without fusion of labia minora | Effects are dose and stage dependent; stimulates growth and differentiation of sex steroid receptor-containing tissue |
Angiotensin-converting enzyme inhibitors | | IUGR, oligohydramnios, pulmonary hypoplasia, skull hypoplasia, neonatal anuria, and neonatal death | Risk when used during the second or third trimester over prolonged periods; no teratogenic effect or abortigenic effect when used in the first trimester |
Antibiotics | Chloramphenicol | Neonatal cardiovascular collapse in women treated near term | |
| Nitrofurantoin | Hemolysis, anemia, hyperbilirubinemia, especially in glucose-6-phosphate-dehydrogenase-deficient infants | |
| Streptomycin; gentamicin, tobramycin, amikacin | Interference with hearing by affecting the eighth nerve | Relatively low-risk phenomenon, mainly associated with long-term maternal exposure |
| Sulfonamides | Increased bilirubin levels in the newborn and increased risk for kernicterus in exposures near term | |
| Tetracycline | Bone and tooth staining | Effects seen only if exposure is late in the first or during second or third trimester because tetracyclines have to interact with calcified tissue |
Anticonvulsants | Carbamazepine | Upslanting palpebral fissures, epicanthal folds, short nose with long philtrum, fingernail hypoplasia, developmental delay | |
| Diphenylhydantoin | Microcephaly, mental retardation, cleft lip/palate, hypoplastic nails, and distal phalanges | Associations documented only with chronic exposure; risk of malformation appears no greater than 10%; short-term therapy (i.e., prophylaxis of a head injury) is not associated with a substantially increased risk |
| Oxazolidine-2,4- diones: trimethadione, methadione | V-shaped eyebrows, low-set ears with anteriorly folded helix, high-arched palate, irregular teeth, CNS anomalies, severe developmental delay | Characteristic facial features documented only with chronic exposure |
| Valproic acid | Neural tube defects and facial dysmorphology | Small head size and developmental delay have been reported with high doses Risk of spina bifida is approximately 1% Risk of facial dysmorphology may be greater |
Antihistamines | Diphenhydramine | Genitourinary malformation | Not a lot of data on these compounds |
Azathioprine | | Abortion | |
Busulfan | | Stunted growth, corneal opacities, cleft palate, hypoplasia of ovaries, thyroid and parathyroids | Dependability of evidence is doubtful |
Caffeine | | Excessive consumption (>300 mg/day) is associated with IUGR and embryonic loss in some studies | |
Chorionic villus sampling | | Limb reduction defects of the congenital amputation type; orofacial malformations | For chorionic villus sampling performed <9 weeks |
Cocaine | | Microcephaly, vascular disruptive phenomena (limb amputations and cerebral infarction), IUGR, neurobehavioral abnormalities, preterm delivery, fetal loss | Low for disruptive phenomena and high for deleterious effects on fetal outcome |
Cyclophosphamide | | Ectrodactyly, syndactyly, cardiovascular anomalies, other minor anomalies, IUGR | Dose related; at the lowest therapetic dose the risk is small |
Chloroquine | | Deafness | Dependability of evidence: suggestive |
Diethylstilbestrol | | Clear cell adenocarcinoma of the vagina | 1:1000 to 1:10,000 of female fetuses exposed in utero |
| | Vaginal adenosis | 75% of female fetuses exposed before 9 weeks |
| | Increased incidence of genitourinary lesions and infertility in males Increased risk of prematurity | |
Electromagnetic fields | Video display terminals | | No increased risk of abortion or malformations |
| Power lines | | Small or nonexistent |
| Appliances | | Small or nonexistent |
Folic acid antagonists | Aminopterin, Methotrexate | Microcephaly, hydrocephaly, cleft palate, meningomyelocele, IUGR, abnormal cranial ossification, reduction in derivatives of first branchial arch, mental retardation, postnatal growth retardation | |
Infectious agents | Cytomegalovirus | IUGR, brain damage with mental retardation, characteristic parenchymal calcification | Fetal infection in approximately 20% of maternal infections; risk of brain damage is moderate after fetal infection in early pregnancy |
| Herpes simplex | Generalized organ infections, microcephaly, hepatitis, eye defects, vesicular rash | Risk of abortion agreed to be increased after herpes simplex 2 infection |
| HIV | Symptomatic maternal HIV infection, other sexually transmitted diseases and opportunistic infections may increase the risk of low birth weight, postnatal CNS deterioration, and perinatal morbidity | Overall risk of vertical transmission is 25-40% |
| Parvovirus B19 | Hydrops fetalis and fetal death | |
| Rubella virus | Mental retardation, deafness, cardiovascular malformations, cataracts, glaucoma, microphthalmia | >80% for infection <12 weeks; 54% for infection at 13-14 weeks; 25% at the end of the second trimester; |
| | Diabetes mellitus or rubella panencephalitis may develop later in life | 100% at term |
| Syphilis | Maculopapular rash, hepatosplenomegaly, deformed nails, osteochondritis at joints of extremities, congenital neurosyphilis, abnormal epiphyses, chorioretinitis | |
| Toxoplasmosis Varicella zoster | Hydrocephaly, microphthalmia, chorioretinitis Skin and muscle defects, IUGR, limb-reduction defects | No measurable increase risk of early teratogenic effects Risk of severe neonatal infection is high if maternal infection occurs in last week of pregnancy |
| Venezuelan equine encephalitis | Hydranencephaly, microphthalmia, CNS destructive lesions, luxation of hip | |
Lead | | Levels <50 μg%: developing CNS in the fetus and child may be susceptible to lead toxicity resulting in decreased IQ and behavioral effects Levels >50 μg%: in children, result in anemia and encephalopathy; may have serious effects on CNS development | |
Lithium carbonate | | Increased incidence of Ebstein's anomaly and other heart and great vessel defects | Clear teratogenic effect in animals; effects in humans still unclear Increased risk on early reports The strength of the association has diminished with publication of more studies |
Mepivacaine | | Bradycardia, death | Dependability of evidence: conclusive |
Methyl mercury | | Minamata disease: cerebral palsy, microcephaly, mental retardation, blindness, cerebellar hypoplasia | At low exposure, the teratogenic effect predominates |
Methylene blue | | Intestinal atresia Hemolytic anemia and jaundice in neonatal period | Risk still not clear for intestinal atresia after intraamniotic injection |
Misoprostol | | Limb reduction defects and Möbius syndrome | |
D-penicillamine | | Cutis laxa, hyperflexibility of joints | Low risk; condition appears to be reversible |
Polychlorinated biphenyls | | Cola-colored babies: pigmentation of gums, nails and groin, hypoplastic deformed nails; IUGR, abnormal skull calcification | Body residues in exposed women can affect pigmentation in offspring for up to 4 years after exposure |
Progestins | | Masculinization of female embryo exposed to high doses of some testosterone-derived progestins | Dose of progestins present in modern oral contraceptives presents no masculinization or feminization risks; no risks for nongenital malformations |
Radiation (external irradiation) | | Microcephaly, mental retardation, eye anomalies, IUGR, visceral malformations | Risk is dependent on dose and time of exposure; exposures from diagnostic procedures present no increased risk of abortion, IUGR or malformations; no measurable risk from exposures ≤5 rad (50 mGy) of x-rays at any stage of pregnancy; exposure of the pregnant uterus to therapeutic doses of ionizing radiation used in radiation therapy significantly increases the risk of aborting the embryo; the fetus is more resistant |
Radioactive isotopes | | Fetal thyroid hypoplasia | I131 after the 8th week of development Radioisotopes used for diagnosis present no risk for inducing abortion |
Retinoids, systemic | Isotretinoin, etretinate | CNS, cardioaortic, ear and clefting defects; microtia, anotia, thymic aplasia, other branchial and aortic arch abnomalities and certain congenital heart malformations | |
Retinoids, topical | Tretinoin | Epidemiologic studies, animal studies and absorption studies in humans do not suggest a teratogenic risk | |
Smoking and nicotine | | Placental lesions, IUGR, increased postnatal morbidity and mortality | |
Thalidomide | | Limb-reduction defects (preaxial preferential effects, phocomelia); facial hemangioma; esophageal, duodenal or anal atresia; anomalies of the external ears, eyes, kidneys and heart; increased incidence of neonatal and infant mortalitiy | |
Thyroid | Iodides, radioiodine, antithyroid drugs (propylthiouracil), iodine deficiency | Fetal hypothyroidism or goiter with variable neurologic and aural damage | |
Toluene abuse | | IUGR, craniofacial anomalies, microcephaly | Occupational exposures should present an increase in the teratogenic or abortigenic risk |
Vitamin A | | CNS, cardioaortic, ear and clefting defects; microtia, anotia, thymic aplasia, other branchial and aortic arch abnormalities and certain congenital heart malformations | Exposures <10,000 IU present no risk to the fetus |
Vitamin D | | Supravalvular aortic stenosis, elfin facies and mental retardation | The quality of information upon which the association is suspected is poor; risk may be increased |
Warfarin derivatives | | Nasal hypoplasia, stippling of secondary epiphysis, IUGR, anomalies of eyes, hands and neck, variable CNS anatomic defects (absence of corpus callosum, hydrocephalus, asymmetric brain hypoplasia) | 10–25% risk from exposure during 8–14 weeks' gestation |