Prenatal diagnosis Flashcards
Frequency of abnormalities in LIVEBORNS
Chromsomal abnormality: 0.5%
Mendelian disorder: 1%
Polygenic/multifactorial: 1%
unknown etiology: 2-3%
Recurrent risk after birth of child with chromosomal abnormality?
T21 1.5%
or the maternal age related risk, whichever is higher
Recurrence risk for children with NTD
Recurrence Risk:
o For mother with NTD: 5%
o For couple with previous affected child: 2-3%
o For couple with 2 affected children: 6-10%
Microarray analysis
- to find small deletions or duplications (copy number variants)
- Case presentation:
o Amnio = 46 XX, t(9;14)(p23;q23)
o Apparently balanced translocation between chromosome 9 and 14
o Parents have normal karyotype - Microarray analysis can detect abnormalities below the level of detection of a routine karyotype, as well as whole chromosome abnormalities
- May detect CNV of unknown significance
- CANNOT detect balanced translocations, inversions, low level mosaicism, or point mutations
- Most beneficial when US identifies anomaly
- With IUFD/stillborn cells won’t grow in culture for karyotype, but can be assed by microarray
What can microarrays NOT detect
Balanced rearranagement
Chance of multifactorial inheritance with cleft lip?
1-5%
What are considerations of ultrasound? Based on thermal and mechanical effects?
- Thermal bioeffects refer to heat generated within or around cells exposed to ultrasound
- Mechanical effects refer to potential impact on tissue from phsiical forces generated by ultrasound waves, such as radiation, streaming, free radicals, and cavitation
- ODS (output display standard) – an approximation of risk of thermal injury is the therma index (TI); and the standard for mechanical mechanisms is the mechanical index (MI)
- A low risk of thermal or miechanical bio effects is seen with TI or MI value of < 1, and if ultrasound machine is capable of producing output levels of greater than 11, then either the TI or MI must be displayed on the screen
- Recommended scanning time with TI 0.5-1 = < 60 minutes; if TI 1-1.5 = < 30 min
Microarray diagnoses and anomalies
Microarrays analysis detects clinically relevant deletions or duplications in 6% of fetuses with structural anomaly and normal karyotype
Acrania/anencephaly, recurrent risk
Lethal, multifactorial, IDDM, antiepileptic drugs
r/o spina bifida
5-6% recurrence risk
Ventriculomegaly
o VM: most common associated anomaly is spina bifida; if cyst, could be DW
Shrinkage of CP at 14 weeks(dialted VS with small CP)
Posterior horn > 10mm
(mom’s trial – fetal surgery for OSB – decreased need for shunting; more babies walking without assistance; but increased PTB rate and uterine dehiscence)
Agenesis of the corpus callosum
Dilated posterior horns
Absent CSP
If isolated, normal outcome in 90% of cases
Tear drop/wide posteriorly
CC is formed at 22 weeks
Holoprosencephaly
single ventricle; fusion of thalami; midline defects (cyclopia, clefts, proboscis)
Recurrence: 6%
Dx: semilobar = separate ventricles except frontal horns
Hydrancephaly
: fluid filled cranium; no cortex liquefied brain
Work up: thrombophilia – thrombosis of internal carotids can cause this
Porencephaly
o Porencephaly: result of infarct
Communicates with lateral ventricles; arachnoid cysts does NOT communicate
One or more cystic cavities communicating with ventricles (infarction or hemorrhage)
Prognosis: related to size and location of lesion; development may be normal
Schizencephaly
clefts connecting the lateral ventricles with sub-arachnoid space – absent CSP
Occluded MCA thrombophilia
Prognosis: severe neurodevelopmental delay
Schizencephaly
clefts connecting the lateral ventricles with sub-arachnoid space – absent CSP
Occluded MCA thrombophilia
Prognosis: severe neurodevelopmental delay
Arachnoid cyst
o Arachnoid cyst: not communicating with ventricles; one or more cystic cavities
No blood flow
Prognosis: related to mass effect; development may be normal (80%)
Encephalocele
o Encephalocele: skull defect (75% occipital); herniated brain tissue
Diff dx: meckel gruber; amniotic band syndrome
Prognosis: depends on amount of brain tissue; 80% are impaired)
Meningocele
o Meningocele: skull defect with no herniated brian tissue
Prognosis good
Vein of Galen
o AV malformation: Vein of Galen
Midline cystic tubular structure posterior to the thalamus with blood flow
3rd trimester MR should be done
Prognosis:
* Alive and well (35%); alive and MR (15%); Overall PND rate (55%)
Intracranial tumors
o Intracranial tumors: usually distorted intracranial anatomy; prognosis usually poor
Craniopharyngioma
Teratoma
Undifferentiated tumor
Intracranial hemorrhage
o Intracranial hemorrhage: r/o AIT (50%)
Test mom for anti platelet antibodies
Cleft lip
o If have cleft lip: have 75% chance of having cleft palate
Worse prognosis = bilateral cleft
Nuchal fold vs cystic hygroma and diagnoses associations
- Nuchal fold/nuchal edema – think T21
- Septated cystic hygroma – think 45 XO
Cystic hygroma
- Cystic hygroma:
o Multiseptated cystic masses; intact skull and spine
o Hydrops present in 80%
o Prognosis good if isolated
Fetal goiter
- Fetal goiter: if hypothyroid: thyroxine injected into amniotic sac
o If hyperthyroid: PTU/Tapozole for mom
o Enlarged thyroid below level of larynx; poly in 3rd trimester
o r/o maternal grave’s disease; 80% are hypothyroid
o prognosis: good if euthyroid at birth
CHAOS
- CHAOS (congenital high airway obstruction Syndrome)
o Prepare for EXIT – c/s; use of relaxants; delivery of head to the shoulders – allow enough time for bronchosopic evaluation of airway and tracheostomy placement
Sacrococcygeal teratoma
- Sacrococcygeal teratoma: huge vascular teratoma from the top of the sacrum; intact spine
o w/u: rule out AV shunting, CHF, hydrops
o prognosis: perinatal morality (50%) due to PTD or hydrops
o without surgery, malignant transformation (80% by 4 months)
o 1st sign of CHF = pericardial effusion, then ascites
Hemivertebrae
- Hemivertebrae
o r/o VATER, Klippel-Feil, Noonan’s , sirenomelia/caudal regression, Carco-Levin
Congenital diaphragmatic hernia
- CDH: 95% are left sided
o Left: mediastinal shift to the R
Absence of normally placed stomach
Liver in chest (50%)
o Right: mediastinal shift to the left; GB in the chest; normally placed stomach
o Portal vessels in the chest
4CV cardiac anomalies
TEF
- TE Fistula/Esophageal atresia:
o Absent stomach; poly
o Dilated proximal esophageal pouch
o Survival 95% if isolated
BPS
- Pulmonary sequestration:
o White lesion (lower lobes or upper abdomen); feeding vessel from aorta
o Diff dx: CCAM type III
o Prognosis: good if isolated; poor if hydrops
Abdominal anomalies- Duodenal atresia
- Duodenal atresia:
o Associated anomalies 20% (*cardiac); performe fetal echo)
o Prognosis: good
Abdominal anomalies- Duodenal atresia
- Duodenal atresia:
o Associated anomalies 20% (*cardiac); performe fetal echo)
o Prognosis: good
Diagnosis of fetal SBO
- SBO: more than 2 fluid filled areas in the abdomen; peristalsis
o Diff dx: meconium illeus, volvulus, Hirschsprung, abdominal cysts
o r/o T 21; the higher the obstruction, the more the poly
Body stalk anomaly
- Body Stalk: omphalocele, severe kyphoscoliosis and a rudimentary UC; liver attached to placenta
GU- renal agenesis
- Renal agenesis: anhydramnios (by 16 weeks); no bladder; flattened adrenals; absent renal arteries
o Work up: renal ultrasound of parents (15% have unilateral renal agenesis)
o Prognosis: recurrence 3% (unless syndromic)
PCKD (Potter Type I)
o Large, echogenic kidneys; may have oligo and nonvisualized bladder, may not be diagnosed until 24 wk
o r/o meckel gruber – polycystic kidneys and omphalocele
o amnio CVS with microarray
o recurrence = 25%
Multicystic kidney disease (Potter type II)
- Multicystic kidney disease (Potter type II)
o Kidneys replaced by multiple non-communicating cysts of variable sizes; nonvisualized bladder if bilateral; oligo (if bilateral)
o Rule out associated anomalies (cardiac, chromosome, renal agenesis)
o Good prognosis if unilateral
Adult polycystic kidney disease (Potter Type III)
- Adult polycystic kidney disease (Potter type III)
o US usually normal
o Large kidneys with non-communicating cysts of variable sizes
o 30% have cysts in liver, pancrease, splee, lungs
o Cerebral aneurysms (20%)
o Diff dx: mendelian disorders; genetic syndromes
o Work up: amnio/cvs for microarray
r/o tuberous sclerosis, Jeune syndrome, sturge-weber syndrome, meckel gruber, zellweger syndrome
o Recurrence = 50%
Candidates and considerations for in utero shunting for uropathies
- Consideration for in –utero shunting:
o Potential candidates:
Bilateral mod-sev hydronephrosis and normal cortical echogenicity
Severe megacystitis and decreasing AFV or oligo
Normal levels of urinary Na, Ca, and b2 microglobulin
o Poor prognostic criteria:
Bilateral multicystic or echogenic kidneys suggestive of renal dysplasia
Anhydramnios
High urinary Ca, Ca, and b2 microglobulin levels
Limb anomalies
Poor prognostic factors for skeletal dysplasia
FL/AC < 0.16
Small (bell shaped) thorax
Short ribs
Marked bowing
Cloverleaf skull
Differential for club food
Idiopathic
Spina bifida
T18
Pena-Shokier
ABS
Arthrogryposis
Skeletal dysplasis
Thanatophoric dysplasia (type I and II) – 3rd trimester diagnosis
o Severe shortening of the limbs
o Narrow thorax
o Large head with prominent forehead
o Telephone receiver femurs (type I)
o Cloverleaf-shaped cranium (type II)
Achondroplasia (3rd trimester)
o Heterozygous:
Limb shortening (after 22 weeks)
Microcephaly
Frontal bossing
Normal intelligence and life expectancy
o Homozygous:
Small thorax – lethal
Overall risk of congenital anomalies in newborns
3-5%
Principles of teratogens
Teratogens:
- An agent which acts on developing embryo or fetus to create a structural abnormality or a deviation from normal morphology or function
- Principle 1: susceptibility depends on genotype of conceptus and how it interacts with environmental factors
o Classic: fetal hydantoin syndrome: related to metabolic defect in fetus
- Principle 2: susceptibility of conceptus to teratogens varies with developmental stage at time of exposure
o When does embryonic period of development end and fetal period begin?
At the end fo the 10th completed week after menstruation
o “fetal period effects”
May have substantial effect in CNS leading to altered behavior in life
Differences may not even be recognizable until long after birth
- Principle 3: Teratogenic agents act non-randomly on developing cells and tissues
- Principle 4: final manifestations of abnormal development are death, malformation, IUGR< and altered function
o Largely dependent on which stage of development exposure occurred
- Principle 5: For an adverse effect to cocur, an agent must reach conceptus
o Placental passage
o Large molecules (MW > 1000) do not easily cross the placenta
- Principle 6: amount of abnormal development increases in degree with dosage of agent exposed
o May vary from no effect to lethal with same agent
FDA categories
- A: controlled studies in women fail to demonstrate risk to fetus
- B: either animal studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women OR animal studies show adverse effect that was not confirmed in controlled studies in women
o Tylenol, narcotics, prednisone - C: animal studies show adverse effects AND there are no controlled studies in women OR studies in women and animals are not available
o Phenergan, lorazepam - D: posistive evidence of human fetal risk but benefits may be acceptable
o ACE I, PTU, warfarin, valproic acid, lithium, magnesium sulfate - X: studies have shown fetal risk in pregnant women clearly outweight any possible benefit
o DES, danazol, thalidomide, isoretinoin
Metabolic conditions that cause anomalies
- DM:
o Risk of anomalmies of poorly controlled is 11%
o NTD, CHD, renal/GI, skeletal/sacral
o HbA1c 10% - 25% risk of anomaly - Phenylketonuria: inborn error of phenylalanine hydroxylase leading to toxic accumulation of phenylalanine
o Treated from infancy with dietary restriction
o Normal growth and development
o If off diet prior to conception, toxic levels will affect fetus
Causes microcephaly and MR
Complex cardiac defects
o Autosomal recessive; check FOB status
o Recommend against aspartame in pregnancy because of high phe content
Mercury
- Mercury:
o Convered in muscle to methylmercery
o Fetal neurologic damage with psychomotor retardation
o Fish consumption of coated grains/contaminated fish
o Largest amount in large predator fish
o Canned tuna has less; usually limit to 2 cans/week in pregnancy
Lead
- Lead: risk for IUGR and MR
o Lead levels should be < 25 micrograms/dl; ideally less than 10
Fetal alcohol syndrome
- IUGR, MR, microcephaly, short palpebral fissures, smooth philthrum and thin upper lip, CHD, small 5th fingernail
- Effects seen with 2 drinks/day
- No lower limit to exposure known
Fetal hydantoin syndrome
- Growth delay, MR, wide anterior fontanel, metopic ridging, hypertelorism, broad flat nasal bridge, bowed upper lip, cleft lip and palate, hypoplastic distal phalanges and nails, hirsutism
- Affects 10% of fetuses exposed to dilantin
- Dilatin metabolized to dilantin epoxide; fetuses homozygous deficient for dilantin epoxide hydrylase have fetal dilantin syndrome; can be diagnosed through parental carrier status and amnio
- Tiny nails
- Valproic acid: 1% risk for NTD
Fetal Warfarin syndrome
Fetal Warfarin syndrome:
- Exposure during 6-9 weeks; 1/3 affected
- Appearance: nasal hypoplasia nd depressed nasal bridge; stippling of epiphyses, fingernail/fingertip hypoplasia, LBW, MR
Retinoic embryopathy
Retinoic Embryopathy:
- Isotretinoin (Accutane) exposure: 35% embryopathy if used > 2 weeks post conception
- Appearance: abnormalities of 1st and 2nd pharyngeal arches surrounding 1st pharyngeal cleft
- Microtia (small ears), anotia, micrognathia, hypertelorism, conotruncal cardiac defects, hydrocephalus, microcephaly
Fetal thalidomide syndrome
- Marketed for morning sickness in 50’s; no abnormalities in animal testing
- Malformation produced in tissues of mesodermal origin related to time of ingestion; single dose produced syndrome
- Affects: long bone development; limb reductions
o External ear abnormalities, normal intelligence, fusion of fingers - Absolute risk: 20% of those exposed
- Phocomelia – hand and feet close to the trunk (no long bones)
Effects of tetracycline
- Tetracycline: adverse effect on fetal teeth and bones
o Medication complexes with calcium orthophosphate; leads to bright yellow teeth
o Teeth undergo calcification at 5 months; use after causes staining of enamel
Effects of tetracycline
- Tetracycline: adverse effect on fetal teeth and bones
o Medication complexes with calcium orthophosphate; leads to bright yellow teeth
o Teeth undergo calcification at 5 months; use after causes staining of enamel
Substance use and fetal risks
Illicit Drug use:
- Marijuana: mild growth delay
- Opiates: increased risk for IUGR and risk for IUFD
- Amphetamines: cleft lip/palate, IUGR
- LSD: no anomalies
- PCP: postnatal irritability
- Cocaine: no pattern, but increased risk of:
o Genitourinary anomalies
o Cardiac anomalies
o CNS anomalies
o Ophthalmologic anomalies
o Limb anomalies
o Related to vasospasm and hypoxia
o Maternal effects: increased risk of elevated HR/BP; abruption, PPROM, LBW, previa
