Q4: Biophysical Profile, Multiple Gestation, & Skeletal Dysplasia

What is the purpose of the biophysical profile?

• Evaluate fetals well-being, detect dysplasia, identify at risk from death, and facilitate management

What two requirements must be present if a fetus is to have normal biophysical activity?

• NST = reactive

• AFI = more than 5cm

List 3 ways the fetus responds to an inadequate placental supply of oxygen

• Loss of HR accelerations

• Decreased body movement and breathing

• Hypotonia

• Decreased amniotic fluid volume

What is prolonged cessation of fetal activity strongly suggestive of?

• Hypoxemia, fetal demise, or adverse outcomes in pregnancy

List 5 other factors that can alter biophysical activity?

• Monotonous picket-fence breathing or gasping

• Seizures

• Sleep-wake cycles

• Partial extension or flexion of an extremity w/o quick return

• Premature aging of the placenta (grade III)

How can we differentiate the asphyxiated fetus from a normal fetus in quiet sleep?

• 40 minutes accommodates fetal sleep-wake cycle

• Assess heart rate variability

What are the five components of the biophysical profile?

• Fetal tone

• Movements

• Breathing

• Amniotic fluid

• NST

Which components are considered acute markers of fetal well-being?

• NST and movements

• Biophysical profile and fetal heart rate monitoring

Which component is considered a chronic marker of fetal well-being?

• NST

• Fetal tone

• Amniotic fluid

Why does oligohydramnios occur in the asphyxiated fetus?

• Placental dysfunction may result in diminished fetal renal perfusion

At what gestational age is biophysical profile testing generally started?

• 26-28 weeks

How long is the exam?  What is the scoring method?

• 30 minutes

• Fetal tone, movement, breathing, heart rate, and amniotic fluid volume; 2 points each, maximum score of 10

List the normal & abnormal criteria for each of the five components

• Fetal breathing movement – 1 episode for 30 secs continuous during a 30-min observation

• Gross body movement – 3 discrete body or limb movements in 30 mins, unprovoked. Continuous movement for 30 mins should be counted as 1 movement.

• Fetal tone – active extension & flexion of at least 1 episode of limbs or trunk

• Fetal heart rate (FHR) – AKA the nonstress test. At least 2 episodes of FHR changes of 15 beats/min & at least 15 secs duration in a 20-min period

• Amniotic fluid index (AFI) – 1 pocket of AF at least 2 cm in 2 perpendicular planes or AFI total fluid measures of 5-22 cm

What is the incidence of twins in North America?

• 33%

What is the perinatal death rate for twins compared to singletons?

• 7-10 times greater

What is the most common reason on physical exam for suspecting a multiple gestation pregnancy?  What are other differentials for this finding?

• Larger than expected uterine size, patient’s pregnancy symptoms seem excessive (ex. Hyperemesis gravidarum), and patient became pregnant using assisted reproductive technology

• Differentials: misdated pregnancy, polyhydramnios, uterine fibroid tumors, cysts, and hydatiform mole

What are other physical & lab findings for suspecting a multiple gestation pregnancy?

• Elevated maternal serum alpha fetal protein (MS-AFP)

What is the role of sonography in the evaluation of a multifetal pregnancy?

• Determine # of fetuses

• Chorionicity/amnionicity

• Presentation

• Location of placenta

What is a monozygotic (MZ) twin? Discuss the incidence of MZ twins worldwide, factors that influence the incidence of MZ twins, its influence on the incidence of anomalies in twins, & percentage of twins that are monozygotic in North America

• Monozygotic twin = identical twin (30% of twins)

• One sperm + one ovum into one zygote; same genetic makeup; contemporaneous (“clones”). Timing of cleavage determines the type of placentation and the likelihood of complications

• 1 in 250 pregnancies

What is a dizygotic (DZ) twin? Discuss the percentage of twins in North America that are dizygotic, factors that affect the incidence of DZ twins, & the incidence of anomalies in DZ twins compared to singletons

• Fraternal (70% of twins)

• Two fertilized ova; implants in separate uterus

• Varies by race, geographic area, maternal age, and availability of assisted reproductive technology

• DC/DA = 18-32% of monozygotic twin, MC/DA = 70% of monozygotic twins, and MC/MA = 1% of monozygotic twins

What is the hallmark sonographic image demonstrating a multifetal pregnancy?

• More than one head in an image

What may mimic an early twin gestation pregnancy?

• Marginal subchorionic hemorrhage

What does chorionicity & amnionicity refer to & what is their significance?

• Chorionicity = # of placentas; help determine specific risks associated with different types of chorionicity or amnionicity.

• Amnionicity = # of amnions that surrounds the fetus in multiple pregnancy; pregnancies with one amnion = monoamnotic, twins or triplet pregnancies with 3 amnions = triamniotic

What are the possibilities of chorionicity & amnionicity of a DZ twin pregnancy?

• Each zygote forms its own placenta

• Each fetus has its own chorion and amnion; diamniotic-dichorionic twin gestation

What are the possibilities of chorionicity & amnionicity of a MZ twin pregnancy & what determines them?

• Monozygotic twin pregnancy = one fertilized egg splits into two embryos

• Chorionicity and amnioticity depend on when the zygote splits after fertilization

• Timing of embryonic division determines where one or two chorions and amnions develop

• Fertilization by a single sperm confirms monozygosity but placental characteristics depends on when single embryo splits

KNOW how to determine chorionicity & amnionicity in the 1^st, 2^nd, & 3^rd trimesters

• 1^st trimester = done by EV in 8 weeks gestation, # of gestational sacs determine number of chorions, evaluate for presence of yolk sac, embryo, and cardiac activity, and determine gestational age

• 2^nd and 3^rd trimester = Dichorionic (2 separate placentas or a merged one, different or same fetal sex, thick membrane, and twin peak sign). Monochorionic/diamniotic (single placenta, same sex, and thin membrane). Monochroionic/Monoamniotic (single placenta, same sex, no membrane, and entangled cords)

Under what circumstance could a monochorionic (MC) twin pregnancy be mistaken for a dichorionic (DC) twin pregnancy?

• Placenta appears fused together, making it difficult to differentiate number of placentas

What is the “twin peak” sign?  If seen, what is its significance? If not seen, what is its significance?  What is the significance of the “T” sign?

• Aka. lambda sign; produce by proliferating chorionic villi growing into the potential space b/t the 2 layers of chorion in the intertwin membrane.

• Seen = dichorionicity; not seen = monochorionicity (especially in the 2^nd or 3^rd trimester)

• 2 layers of amnion extended perpendicular to the single placenta

When is the evaluation of the thickness of the interfetal membrane most reliable?  What happens to it as the pregnancy progresses?

• Near the end of the 1^st trimester (20 weeks)

• Pregnancy progresses = harder to see the interfetal membrane

What are the limitations associated with evaluating the thickness of the interfetal membrane?

• Assess membrane close to the placental attachment site and avoid membrane perpendicular; causes thin membrane to appear thick

What may mimic the interfetal membrane?

• Amniotic band

• Uterine synechiae

• Partial uterine septations

• Intrauterine bands

List 3 reasons why the interfetal membrane may not be visualize?

• Thin/ not perceptible

• Monoamniotic twin pregnancy

• Too early to visualize

What are the leading causes of perinatal mortality in multiple gestations?

• Premature delivery and IUGR; 2-3 times higher mortality for MC twins than DC twins

How is discordant growth defined in the 1^st trimester & later in pregnancy? What is its significance in the 1^st trimester & later in pregnancy?  What are the sonographic findings that indicate growth discordance later in pregnancy?

• Significant difference in growth rates between multiple gestations

• 5+ days difference in estimated gestational age; CRL normal in 1st trimester; 28-30 weeks twins growth rate is similar to singletons

• Sono findings: difference birth weight of 20% or more increases significantly for morbidity and mortality compared to twins with nearly equal weight

List a four causes of discordant growth in twins

• Uteroplacental insufficiency

• IUGR

• TTTS

• Velamentous cord insertion

• Single umbilical artery

Why do monochorionic twins have a higher mortality rate than dichorionic twins?  This condition gives rise to what 3 abnormalities unique to monochorionic twins?  Discuss each abnormality regarding their specific cause & sonographic findings

• Shared placenta creates potential for vascular anastomoses; uneven distribution of blood between twins (TTTS) + hemodynamic instability

• Sono findings = oligohydramnios (donor twin), polyhydramnios (recipient twin), and “stuck twin” (donor twin appears immobile and trapped against uterine wall due to severe oligo, AV anastomoses; donor twin to become anemic and recipient twin to become polycythemic

What is TOPS & what are some its causes?

• Twin oligohydramnios polyhydramnios sequence

• Monochronic twin pregnancy (two fetuses share same placenta), unbalanced blood exchanged (recipient = poly, larger, bladder seen, hydrops; donor = “stuck twin”, smaller, and no bladder seen)

What are the sonographic findings in monoamniotic twins?

• Visualization of two cord insertion into chorionic plate of placenta in very close proximity to one another

• Cord entanglement or Doppler different heart rates in entangled cord

What is the mortality rate of monoamniotic twins?  Why is it so high?

• High mortality rate due to umbilical cord entanglement

What causes twins to be conjoined? What is their zygosity, chorionicity, & amnionicity? What is the most common type of conjoined twin?  What is craniopagus?

• Incomplete cleavage of embryonic disc by day 13

• Monochorionic monoamniotic twins

• Most common = omphalopagus or thracopagus twins

• Joined at the head

What congenital anomalies in MZ twins occur late & are due to limited space?  What are the early defects of development?  What is the concordance rate of the majority of anomalies in MZ twins?  How often are genetic defects concordant in MZ twins?

• Limb defects and facial deformities

• Neural tube defects and congenital heart diseases

• High; often exceeding 60%

• More than 90% of the time

How does a molar pregnancy with coexisting fetus come about?

• Occurs when fertilized egg develops abnormally, leading to a hydatidiform mole while simultaneously developing a normal twin

• Rare; abnormal placental growth alongside a viable fetus

What is a heterotopic pregnancy?  What are predisposing factors for heterotopic pregnancy

• Presence of IUP and ectopic pregnancy simultaneously

• Patients undergo ovulatory induction or IVF

What is superfetation & superfecundation?

• Superfetation = second conception during pregnancy; gives rise to embryos of different ages in the uterus.

• Superfecundation = fertilization of 2+ ova from same cycle by sperm from separate acts of sexual intercourse

What is the most common fetal & maternal complication of multiple gestations?

• Prematurity

• IUGR

List 6 other maternal complications that occur with higher incidence in multiple gestations

• Polyhydramnios

• Hemorrhage

• Miscarriage

• Anemia

• Operative delivery

• Maternal mortality

• Pre-eclampsia

• Hyperemesis gravidarum

What tissues are abnormal in skeletal dysplasia?

• Chondro-osseous tissue caused by single-gene disorders with prenatal and postnatal manifestations

What effect can this have on the appearance of bones?

• Severe micromelia, proximal bones (rhizomelia), cloverleaf deformity (kleeblattchadel skull), narrow thorax with shortened ribs, protuberant abdomen, frontal bossing (bludging forehead), hypertelorism (widely spaced eyes), and flat vertebral bodies (platyspondyly).

What are the two general classes of short-limb skeletal dysplasias?

• Lethal skeletal dysplasias

• Nonlethal or variable prognosis skeletal dysplasias

What six additional a require examination if a short-limb skeletal dysplasia is suspected?

• Long bones

• Spine

• Thorax

• Hands and feet

• Calvarium

• Facial feature

What is the definition of an abnormally short femur?

• Below -2 standard deviations (SD) for GA

If an abnormally short femur is present, when should a follow-up ultrasound be performed?

• Ultrasound should be done in 3-4 weeks to evaluate interval growth to assess potential changes in the fetus's growth

What results on the follow-up ultrasound would suggest the fetus does NOT have a skeletal dysplasia?  What results would suggest the presence of a skeletal dysplasia?

• Interval growth is norma; = does not have skeletal dysplasia

• Further deviation from the mean by at least 1 SD suggests presence of skeletal dysplasia or severe IUGR

• FL measures below -4SD for GA = skeletal dysplasia

What results would be suggest a high likelihood of a skeletal dysplasia?

• FL = < 5mm below the -2SD point

What is rhizomelia, mesomelia, acromelia & micromelia?

• Rhizomelia = shortening of the proximal segment (femur & humerus)

• Mesomelia = shortening of the middle segment (radius, ulna, tibia, & fibula)

• Acromelia = shortening of the distal segment (hands & feet)

• Micromelia = shortening of the entire limb (mild, mild/bowed, or severe)

Other than shortening what other bony characteristics should be assessed?

• Shape, contour, and density of the bones should be assessed for the presence of: bowing, angulations, fractures, and thickening.

What are the sonographic appearances of fractures? Of demineralization?

• Angulations/ interruptions in the bone contour or as thick, wrinkled contours corresponding to repetitive cycles of fracture & callus formation

• Decreased/ absent acoustic shadowing

What abnormalities of the spine should we look for?

• Segmentation anomalies, kyphoscoliosis, platyspondyly, demineralization, myelodysplasia, and caudal regression syndromes

What measurements of the chest can be made?  Where are these measurements made? What fetal part is the chest compared to?

• Thoracic circumference (TC) measured at level of the 4-chamber heart and compared to nomograms

• Ratio of < 0.8 = abnormal

• Thoracic length (from the neck to the diaphragm) and ribs are assessed to determine if they are short

What is the most important factor in determining the lethalness of an anomaly? What findings imply this condition?

• Presence of pulmonary hypoplasia

• Diagnosis of a lethal skeletal dysplasia based on pulmonary hypoplasia

What features of the ribs should be evaluated?

• At the level of 4-chamber cardiac view; encircle at least 70-80% of the TC

• Relatively horizontal plane

What abnormalities of the hands & feet should we look for?

• Clubfoot or clubhand

• Hitchhiker thumb (abducted thumb); diastrophic dwarfism

• Hand and foot abnormalities occurs with skeletal dysplasia

• Hand anomalies: missing digits, fused digits, or a split hand (lobster-claw deformity), polydactyly.

What abnormalities of the cranium & face should we look for?

• Macrocranium, frontal bossing, cloverleaf skull deformity, and underlying brain abnormalities.

• Facial abnormalities: saddle nose, hypertelorism, and left lip & palate

What are the main characteristics of  lethal skeletal dysplasias?  What are two associated findings.

• Severe micromelia and small TC with pulmonary hypoplasia

• Thickened skin folds and polyhydramnios

What skeletal dysplasias account for 60% & 2/3 of lethal skeletal dysplasias?

• Thanatophoric dysplasia

• Achondrogenesis

• Osteogenesis imperfecta type II

What is the most common lethal skeletal dysplasia?

• Thanatophoric dysplasia

What are the findings in the most common skeletal dysplasia?

• Severe micromelia w/ rhizomelic predominance & macrocrania (disproportionately large head)

• Skin folds = thickened & redundant

• Clinical presentation = caused by large-for-date measurements secondary to polyhydramnios

What are the findings in Type I & Type II?

• Type I = “telephone receiver” shape of extremities, bowed/curved metaphysis’ at ends of shortened tubular bones

• Type II = femurs straight w/ flared metaphysis’, cloverleaf skull (most common), trilobed of skull in coronal plane

What are the findings of achondrogenesis?  How do the findings differ from thanatophoric dysplasia

• Achondrogenesis; 2nd most common lethal skeletal dysplasia

• Chondrodysplasias characterized by: severe micromelia, macrocranium, decreased TC & trunk length, decreased mineralization

• Differ from thanatophoric dysplasia = positive family history; both parents affected with heterozygous form of achondroplasia

What are the findings of osteogenesis imperfecta type IIA.

• Heterogeneous group of collagen disorders; brittle bones resulting in fractures

• 3 criteria/specific diagnosis of OI type II = FL> 3SD below the mean, demineralization of the calvarium, and multiple fractures within a single bone

What are the findings of congenital hypophosphatasia?

• Severe micromelia, decreased TC w/ normal trunk length, decreased mineralization w/ occasional fractures, cranial vault size remains normal, no macrocrania, and oligohydramnios

What are the differentials for congenital hypophosphatasia & what are the differences?

• Differentials = osteogenesis imperfecta, achondrogenesis, and skeletal dysplasias

• Key differences = patterns of mineralization, bone fragility, and limb length abnormalities

What are the findings of camptomelic dysplasia?

• Short & ventrally bowed tibia & femur, hypoplastic, or absent fibula, talipes equinovarus (clubfoot), hypoplastic scapulae, and bowing may also occur in the upper extremities

What is the most common non-lethal skeletal dysplasia?  What are the sonographic findings?

• Heterozygous achondroplasia

• Mild to moderate forms of rhizomelic limb shortening (more prominent in upper limbs), macrocranium, frontal bossing, depressed nasal bridge, midface hypoplasia, brachydactyly w/ a trident configuration of the hand, interpedicular distances progressively narrow from the upper to the lower lumbar spine, and progressive discrepancy in FL & BPD