Teratogens AM Report: August 1, 2007 Sarah, Rachana, Diana

Teratogens
AM Report: August 1, 2007
Sarah, Rachana, Diana
Periods of Sensitivity During Development
Case Vignette
You are called to the newborn nursery to
evaluate a baby who has dysmorphic
features. The baby was born at term. He
has a wide anterior fontanelle, a broad
depressed nasal bridge, short nose,
hypertelorism, and hypoplastic nails. On
auscultation of his heart, you appreciate a
holosystolic murmur.
What is the teratogen?
Dilantin Exposure
in utero
Fetal Hydantoin Syndrome
• Affects ~10% of babies born to moms on phenytoin
• May alter placental tx of Vit K and metabolism of Vit D
Hemorrhagic Disease of Newborn/ Hypocalcemia
remain small after birth
• Growth: IUGR
• Craniofacial anomalies: microcephaly, midface
hypoplasia (broad depressed nasal bridge, short
nose), cleft lip/palate, hypertelorism, short neck,
ophthalmologic abnormalities
• Cardiac anomalies: pulmonic/aortic valve stenosis,
VSD
• Neurodevelopmental Abnormalities: DD/MR
• Other: hirsutism, hypospadias, hypoplasia of distal
phalanges and nails, digitalized thumbs, rib anomalies
• A preterm baby whose prenatal US were
significant for IUGR is born. She is LBW and
microcephalic. The baby has seizures on day 2
of life and head imaging reveals evidence of
stroke.
What is the teratogen?
COCAINE !!!
Gastroschisis secondary to
maternal cocaine abuse
COCAINE
• Crosses placenta and concentrates in amniotic
fluid
• Associated with:
- placental abruption
- PROM & preterm delivery
- gastroschisis
- vascular malformations
- microcephaly
- neurobehavioral and learning disorders
What is the teratogen?
• You are called to evaluate an infant in the
NICU with contractures, lung hypoplasia,
and craniofacial defects. Similarly, the
infant has renal tubular dysplasia, PDA,
and had prolonged neonatal hypotension.
Answer: ACE Inhibitors!
ACE Inhibitors and the Second
and Third Trimesters
• Most common effects involve kidney,
oligohydramnios, in-utero death, anuria,
and renal failure
• Other effects include hypocalvaria, lung
hypoplasia, and limb contractures
• ARBs demonstrate similar fetal outcomes
How do ACE inhibitors cause
adverse fetal effects?
• ACE inhibitors and ARBs cross placenta
and interfere with fetal renal
hemodynamics
• ACE inhibitor-induced decline in GFR in
fetal kidneys leads to decreased urine
production and oligohydramnios
• Results: limb contractures, lung
hypoplasia, cranial ossification defects,
renal tubular dysplasia, prolonged
hypotension, and PDA
Case Vignette
A mother brings in her newborn for her first visit after
being discharged from the hospital. On exam, the
baby has epicanthal folds, a broad nasal bridge,
anteverted nostrils, a long philtrum and a small
mouth. Knowing the mother’s medical history, you
are especially concerned for a teratogenic exposure
as a cause for the baby’s dymorphic features.
What is the teratogen?
Valproic Acid exposure
in utero
Fetal Valproate Syndrome
• Craniofacial Anomalies: high forehead, epicanthal folds,
broad nasal bridge, anteverted nostrils, long philtrum,
small mouth, cleft lip, microcephaly
• Cardiac Anomalies: Coarctation of aorta, HLHS, aortic
valvular stenosis, ASD, VSD
• Neurodevelopmental Abnormalities: Neural tube defects,
DD/MR
• Other: Long thin digits, hyperconvex nails, hypospadias
Case Vignette
This medication was initially introduced in
the mid-1950s as a mild sedative to help
combat nausea. It was taken off the
market in the 1960s due to unexpected
effects on fetuses. The deformity it best
known to cause is phocomelia.
What is the teratogen?
Thalidomide Exposure in utero
Thalidomide Baby
• Increased risk of miscarriage
• Limb defects: symmetric preaxial limb defects, phocomelia (long
bones of limb are shortened or completely absent); upper limb >
lower limb)
• Craniofacial anomalies: developmental abnormalities of the ear
and eye (deafness, coloboma), and abnormalities of innervation
of the external ocular muscles, the facial muscles, and the tear
glands (crocodile tears: tears produced at inappropriate times,
i.e. while eating)
• Internal organ defects: many affect any organ system
•
Neurodevelopmental Defects: DD/MR, seizure d/o, behavioral
d/o, involuntary movements
Case Vignette
A newborn is evaluated for a heart murmur
and found to have a VSD. History is notable for
lack of prenatal care. At the time of delivery
ultrasound evaluation showed IUGR.
On exam the child is noted to have
symmetric growth retardation, small palpebral
fissures, thin upper lip, and underdeveloped
philtrum.
What is the teratogen?
Alcohol !!
Fetal Alcohol Syndrome
To Diagnose
•
•
•
•
Confirmed maternal EtOH exposure
Characteristic facial anomalies
Growth retardation
CNS neurodevelopmental findings
Characteristic Findings of FAS
• Facial: short palpebral fissures, flat midface, upturned
nose, smooth philtrum, thin upper lip, ptosis (later)
• Growth Retardation: SGA, poor growth postnatally
• Neurodevelopmental: Microcephalic, structural brain
anomalies, hypotonia, irritable/poor bonding
• Behavioral Abnormalities: LD, MR (mean IQ 66), ADHD
• Congenital Defects: CHD (VSD), skeletal deformities,
ophthalmologic problems, hypoplasia of nails
Case Vignette
You are called to deliver a newborn of
mother who did not receive any prenatal
care. At the time of delivery, the baby is
found to have a myelomeningocele and
dysmorphic facial features.
What is the teratogen?
Carbamazepine Exposure in
utero
Carbamazepine Exposure
• May alter placental tx of Vit K and metabolism of Vit
D
Hemorrhagic Disease of Newborn/
Hypocalcemia
• Craniofacial Defects
• Neurodevelopmental Abnormalities: NTD, DD/MR
• Other: Nail Hypoplasia
• A pregnant female has an eating disorder
and is regularly using a “diet pill”
throughout pregnancy. The baby is born
preterm and noted to be irritable, jittery,
and with a high pitched cry.
What is the teratogen?
Amphetamines
•
•
•
•
•
Preterm delivery
IUGR and SGA
Placental abruption
Withdrawal symptoms
Congenital heart disease
What is the teratogen?
• You are in your continuity clinic and see a
patient with Ebstein’s anomaly. What
question should you ask the infant’s
mother about her medical history?
Ebstein’s Anomaly
Answer: Lithium
Summary: Lithium
• Lithium has no documented association
with fetal development
• Soft evidence exists that it is associated
with Ebstein’s anomaly
• Pregnancy class D: evidence of risk, but
benefits to mother may outweigh risks to
fetus
What is the teratogen?
• You are in the GCN, and you are called to
evaluate a 5-day-old infant. You are
concerned because he is tremulous, has a
high-pitched cry, poor feeding, and
diarrhea.
Answer: Heroin…Or Other
Opioids
Neonatal Narcotic Abstinence Syndrome
•
•
•
•
•
•
Tremors
Irritability
Increased wakefulness
High-pitched crying
Increased muscle tone
Hyperactive deep tendon
reflexes
• Exaggerated Moro
• Seizures
• Frequent yawning and
sneezing
• Poor feeding
• Uncoordinated and
constant sucking
• Vomiting and diarrhea
• Poor weight gain
• Nasal stuffiness
• Fever
• Mottling
• Temperature instability
Case Vignette
The anxious parents of a 7 day old baby
bring her back to see you with the concern
that she has been acting different for the
last 2 days. They report restlessness,
jitteriness, and an insatiable hunger. They
also report that she has been difficult to
console and has been sleeping less than
usual. At the time of birth, she was noted to
have a cleft lip but otherwise has been
healthy.
What is the teratogen?
Phenobarbitol Exposure in
utero
Phenobarbitol Exposure
• Exposure during 3rd trimester is most detrimental
• May alter placental tx of Vit K and metabolism of Vit D
Hemorrhagic Disease of Newborn/ Hypocalcemia
• Craniofacial Defects: Cleft Lip/Palate
• Cardiact Defects
• Neurodevelopmental Abnormalities: Risk of withdrawal
presenting at DOL ~4-7. Sx include: overactivity,
restlessness, insomnia, tremors, hypertonicity, vasomotor
instability, and hyperphagia. Withdrawal sx may last up to
weeks or months.
What is the teratogen?
• You are called to evaluate an infant in the
NICU with microcephaly, microphthalmia,
microtia with atresia of the ear canal,
truncus arteriosus, and an absent thymus.
What medicine do you think that the
mother took during pregnancy?
Microtia and Truncus Arteriosus
Answer: Isotretinoin
Summary: Isotretinoin
• Ear anomalies: microtia with or without atresia of the
ear canal
• CNS malformations: hydrocephalus, neuronal brain
migration defects, cerebellar abnormalities
• Severe MR
• Seizures
• Dysmorphic features
• Absent thymus
• Truncus arteriosus
• Pregnancy class X: contraindicated in pregnancy
What is the teratogen?
• You are in the GCN and note one of the
newborns has a depressed nasal bridge, a
short nose, and hypoplastic distal
phalanges. You have x-ray vision, and
you also see stippling of his epiphyses.
Depressed Nasal Bridge and Short Nose
Answer: Warfarin
Summary: Warfarin
• Teratogenic effects during 6th-9th week
• Most common effects are on bone and
cartilage
• Mechanism of teratogenicity may be
related to drug’s interference with posttranslational modifications of calciumbinding proteins that are key to the
development of bony structures
Summary: Warfarin
• Less well-documented risks during any
stage of pregnancy
– Optic atrophy
– Microcephaly
– MR
– Spasticity
– Hypotonia
• Pregnancy risk factor X: contraindicated in
pregnancy
Neonatal Abstinence Scores
• Used to initiate, adjust, and wean
pharmacologic therapy.
• Domains of scoring system
– Vasomotor, metabolic, and ventilatory
disturbances
– CNS disturbances
– Gastrointestinal disturbances
ƒ A full term baby is born SGA and with a
cleft lip. Mom did not have any
infections during pregnancy and had
regular PNC. Her ultrasounds
consistently demonstrated poor prenatal
growth. She denies illicit drug use.
Family history is notable for a 4 mo old
sibling who died from SIDS.
ƒ What is the most likely cause of the
newborn’s findings?
TOBACCO !!!
Tobacco exposure
• Poor prenatal growth:
- Dose related
- symmetric
- up to 5% weight reduction for every
pack per day smoked
• SGA
• Cleft lip & palate
• Placental abruption
• Associated with SIDS