Teratogenic birth defects Flashcards
Definition of a teratogen
VACTERL association
Definition of a teratogen: an environmental factor that causes a permanent structural or functional abnormality, growth restriction, or death of the embryo or fetus
The physical effects of teratogens are widely varied (see individual conditions for specific manifestations):
VACTERL association:
Vertebral, anal, cardiac, tracheoesophageal fistula, renal, and limb abnormalities
defect during the development of embryonic mesoderm
Diabetic embryopathy
Onset: first trimester
Pathophysiology: hyperglycemia → inhibition of myoinositol uptake → abnormalities in the arachidonic acid-prostaglandin pathway → birth defects and spontaneous abortion
Effects
transposition of the great vessels; ventricular septal defect; truncus arteriosus
Neural tube defects
Caudal regression syndrome
aplasia or hypoplasia of the sacrum or lumbosacral spine
Clinical features
paralysis; bladder incontinence
Anorectal malformations and sacral agenesis
Lower limb or foot deformities
Prognosis
infant death
Diabetic fetopathy
Onset: second and third trimester
Pathophysiology: chronic fetal hyperglycemia → fetal hyperinsulinemia + islet cell hyperplasia, insulin-like growth factor, and growth hormones → ↑ metabolic effects and oxygen demand → fetal hypoxemia
Effects
Macrosomia
Polycythemia
Neonatal hypoglycemia and other electrolyte imbalances (hypocalcemia, hypomagnesemia)
Respiratory distress
Hypertrophic cardiomyopathy; polycythemia
maternal Graves disease
Clinical features
Hyperthyroidism: irritability, restlessness, tachycardia, diaphoresis, hyperphagia, poor weight gain, diffuse goiter (can cause tracheal compression), microcephaly (due to craniosynostosis)
May arise directly after birth or delayed up to 10 days later as a result of transplacental maternal antithyroid medication (including propylthiouracil or carbimazole)
Treatment
Neonatal Graves disease resolves within 1–3 months
Infants with symptomatic hyperthyroidism: methimazole and propranolol
Complications: Untreated symptomatic hyperthyroidism in infants can cause cardiac failure and intellectual disability.
maternal hypothyroidoism
Congenital hypothyroidism
Children with congenital hypothyroidism may have general signs and symptoms of hypothyroidism in addition to those typical in neonates
Postpartum:
Umbilical hernia
Prolonged neonatal jaundice
Hypotonia
Decreased activity, poor feeding, and adipsia
Hoarse cry, macroglossia
Congenital iodine deficiency syndrome; impaired development of the brain and skeleton, resulting in skeletal abnormalities (e.g., short stature and delayed fontanelle closure) and intellectual disabilities
Alcohol: Fetal alcohol syndrome (embryo-fetal alcohol syndrome)
Epidemiology Most common cause of intellectual disability in the US! Clinical findings Dysmorphic features Thin upper lip Smooth hypoplastic philtrum Down-slanting, short palpebral fissures Narrow, receding forehead Hypertelorism Microcephaly Features of specific systemic defects Heart defects (mainly ventricular septal defect) Hyperactivity, intellectual disability (e.g., learning disabilities, memory and reasoning deficits, and impaired language development) → problems in social interactions and school performance
Cigarette smoking
Pathophysiology
Nicotine: ↑ catecholamine release → vasoconstriction of uteroplacental blood vessels → compromised blood flow and oxygen delivery to fetus
Carbon monoxide: ↑ COHb causes tissue hypoxia
Effects
Intrauterine growth restriction and low birth weight
Increased risk of preterm labor and miscarriage (e.g., due to placental abnormalities such as placental abruption)
Attention deficit hyperactivity disorder (ADHD) and conduct disorder
Sudden infant death syndrome (SIDS)
Opioids
Placental abruption
Respiratory depression
Neonatal abstinence syndrome
Cocaine
Causes vasoconstriction in the placental vessels
Intrauterine growth retardation and low birth weight
Increased risk of preterm labor and placental abruption
maternal medications
The following drugs are no longer approved for clinical use. See pharmacotherapy during pregnancy for a comprehensive list of teratogenic drugs. Diethylstilbestrol Effects Vaginal clear cell adenocarcinoma Congenital müllerian anomalies Thalidomide Effects: thalidomide embryopathy Symmetrical amelia (complete absence of limbs)
