Fetus and Newborn

TERATOGEN DEFECTS
ACE inhibitor • IUGR, renal failure, Potter-like syndrome, pulmonary hypoplasia, increased risk of orofacial clefts and
and cardiovascular
angiotensin defects (especially cardiac septal defects)
receptor • Mechanism: inhibiting fetal urine production (oligohydramnios) leads to renal dysplasia and renal
antagonists failure, hypoplastic calvaria (skullcap covering the cranial cavity containing the brain is not fully
developed), and IUGR
Alcohol (Fig. 6- • Mental impairment (leading cause in the Western Hemisphere), microcephaly, congenital heart
28 defects (VSD, ASD), attention deficit, diagnostic facial features (upper lip thinning, epicanthal folds,
A, B) flat nasal bridge, short nose, hirsute forehead, and short palpebral fissures)
• Mechanism: acetaldehyde (breakdown product of alcohol metabolism) disrupts cellular differentiation
and growth
(disrupts retinoic acid and hedgehog signaling pathways), disrupts DNA and protein synthesis, and inhibits
cell migration
Amphetamine • Congenital heart defects, IUGR, behavioral deficiencies, learning disabilities, cranial abnormalities, oral
cleft and limb
defects, and abnormal brain development closely resembling those in ill, asphyxiated infants
• Mechanism: neurotoxicity on mature neurons due to the production of reactive oxygen species and nitric
oxide, and p53
activation resulting in apoptosis, and mitochondrial dysfunction
Aspirin • Increased risk of orofacial clefts and cardiovascular defects, especially cardiac septal defects
(acetylsalicylic • Mechanism: acetylsalicylic acid (aspirin) is the only NSAID that irreversibly inhibits cyclooxygenase by
acid) acetylation. Cyclooxygenases produce prostaglandins that play a significant role in keeping the ductus
arteriosus open and increasing blood flow in the placenta.
Carbon • Cerebral atrophy, microcephaly, seizures
monoxide • Mechanism: activation of an inflammatory cascade resulting in oxidative damage and brain lipid
peroxidation (free
radical damage)
Cocaine • Microcephaly, low birth weight, renal agenesis, intestinal atresia, congenital heart disease, urinary tract
abnormalities
(urethral obstruction, hydronephrosis, hypospadias [urethra opens on undersurface of penis])
• Mechanism: disruption of normal growth and development as a result of vascular insufficiency
DES • Vaginal and/or cervical clear cell carcinoma (develops from remnants of paramesonephric ducts; see Fig.
22-3 B)
paramesonephric duct defects (uterine abnormalities, cervical incompetence)
• Mechanism: DES inhibits normal differentiation of paramesonephric structures.
Phenytoin • Nail and distal phalanx hypoplasia, cleft lip and/or palate, neuroblastoma, bleeding (vitamin K
deficiency)
• Mechanism: embryonic hypoxia during susceptible periods. Oxidative stress (free radical damage).
Progesterone • Virilization of female fetus
• Mechanism: progesterone structurally related to testosterone and can virilize female fetuses (enlarged
clitoris)
Retinoic acid • Craniofacial dysmorphisms, cleft palate, thymic aplasia, and neural tube defects
• Mechanism: disrupts Hox gene function (important in determining the different structures that develop
in the anterior- posterior axis)
Statin drugs • IUGR, limb deficiencies, VACTERAL (vertebral, anal, cardiac, TE fistula, renal, arterial, limb)
• Mechanism: interference with Hedgehog proteins, which are key regulators of embryonic growth,
patterning and morphogenesis of many structures; therefore, downregulation of the synthesis of
these proteins may lead to birth defects.
Thalidomide • Amelia (absent limbs), phocomelia (seal-like limbs), deafness
(Fig. 6-29) • Mechanism: oxidative stress and anti-angiogenesis; drug binds to thalidomide-binding protein, cereblon
(CRBN), and
inhibiting its ubiquitin ligase activity
Tobacco • IUGR, low birth weight, prone to sudden infant death syndrome; does not produce congenital
(nicotine) malformations
• Mechanism: oxidative stresses (free radicals)
Valproate • Neural tube defects (valproate is a folate antagonist), autism
• Spina bifida, facial and cardiac anomalies, limb defects, impaired neurologic function, autism spectrum
disorder
• Mechanism: folic acid antagonist (neural tube defects)
• Oxidative stress
Warfarin • Nasal hypoplasia, agenesis corpus callosum, fetal bleeding, death
• Mechanism: hemorrhages into developing organs
Methotrexate • Craniofacial and limb abnormalities
• Mechanism: folic acid antagonist

Tetracycline • Teeth pigmentation, hypoplasia of enamel, retarded skeletal growth, cataract, limb malformations
• Mechanism: crosses the placental membrane and deposits in bones and teeth in the embryo

Lithium • Ebstein tricuspid valve abnormalities

• Mechanism: targets glycogen synthase kinase-3, which is a negative regulator of the Wnt signaling
pathway, which
regulates embryonic patterning and organogenesis
Streptomycin • Ototoxicity
• Mechanism: enters hair cells where it induces cell death via free radicals, disruption of mitochondrial
protein synthesis,
and activation of caspases and nucleases leading to apoptosis

TABLE 6-5 Congenital Infections Associated With Congenital Defects

INFECTION TRANSMISSION CLINICAL FINDINGS
Cytomegalovirus (Fig. Transplacental • Deafness, IUGR, CNS calcification (periventricular in 40% of cases),
6-30 A, B) petechiae (50% of cases), hepatomegaly with jaundice (40% of cases),
thrombocytopenia
• Culture urine (best fluid to culture); urine cytology findings: large cells
with eosinophilic intranuclear inclusions
Herpes simplex type 2 Birth canal • IUGR, vesicular lesions or scarring, keratoconjunctivitis, microcephaly
Rubella (Fig. 6-30 C, D, E) Transplacental • Deafness (sensorineural), PDA, cataract, thrombocytopenia (“blueberry
muffin” rash), hepatomegaly
Syphilis (Fig. 6-30 F, G; Transplacental • Occurs after 20 weeks gestation
Fig. 18-3 H) • Hepatitis, saddle nose, blindness, notched/peg teeth
Toxoplasmosis Transplacental • Blindness (chorioretinitis), deafness (sensorineural), CNS calcification
(Fig. 26-16 D, E) (basal ganglia), IUGR, hydrocephalus, hepatosplenomegaly
• Pregnant women should avoid cat litter, raw meat
Varicella Transplacental • Limb defects, mental impairment, blindness (chorioretinitis), cataracts,
skin scars
HIV Transplacental, birth • Oral thrush, recurrent bacterial infections, intracranial calcification, failure
canal, breast-feeding to thrive