NT AND ANEUPLOIDY

.Monosomics for all human autosomes die in utero.A sex-chromosome monosomic complement of 44 autosomes + 1 X produces the phenotype of Turner syndrome.The most common type of viable human aneuploid is Down syndrome occurring at a frequency of about 0.15 percent of all live birthsThe only other human autosomal trisomy to survive to birth are afflicted with either trisomy 13 (Patau syndrome) or trisomy 18(Edwards syndrome). Trisomies chromosome 2, 16, and 22 are relatively common in abortuses but never survive to birth. Trisomy of the sex chromosomes is possible, such as in (47,XXX), (47,XXY), and (47,XYY).

NUCHAL TRANLUCENCY

USG MARKERS NT - MOST ROBUST MARKER NASAL BONE TRICUSPID FLOW DUCTUS VENOSUS FLOW

WHY FIRST TRIMESTER COMBINED SCREENING MA+NT+BIOCHEMICAL MARKERS  Advantages compared to second trimester biochemical screening  include: Earlier diagnosis (11-14 weeks) Higher detection rates  for fetal Down syndrome (80-90% or perhaps even higher compared to 75% for the second trimester "quad" screen and 60-70% for the older "triple" screen) Detection of most major chromosome abnormalities other than trisomy 21 Acts as a nonspecific marker for other birth defects  including some major cardiac defects and syndromic conditions Can detect a number of major structural birth defects associated with normal chromosomes The primary disadvantage is Narrow window of entry (11-14 weeks with ideal entry at 11-12 weeks).

NT AND ANEUPLODY

MATERNAL AGE + NTM A + NT + BIOCHEMICAL MARKERS

M A + NT + B M + NB/DV FLOW/TCV FLOW.

RISK 1 TO 50 NB –N NO CHANGE IN RISKRISK UPTO 1 TO 1000 NB- N RISK REDUCED NB-AB RISK INCREASEDHYPOPLASTIC NB ALL OTHER MARKERS N –REPEAT SCAN

REVERSE a WAVE RISK ALWAYS INCREASED

NT AND EUPLOID FETUS

INCREASED NT A/W INCREASED FETAL MORTALITY INCREASED NT A/W STRUCTURAL ABNORMALITIES

MAJOR CARDIAC DEFECTS DIAPHRAGMATIC HERNIA EXOMPHALOS SKELETAL DEFECTS BODY STALK ANOMALIES

Cardiac defectsDiaphragmatic herniaExomphalosAchondrogenesis type IIAchondroplasiaAsphyxiating thoracic dystrophyBeckwith-Wiedemann syndromeBlomstrand osteochondrodysplasiaBody Stalk anomalyCampomelic dysplasiaEEC syndromeFetal akinesia deformation sequenceFryn syndromeGM1-gangliosidosisHydrolethalus syndrome

Jarcho-Levin syndromeJoubert syndromeMeckel-Gruber syndromeNance-Sweeney syndromeNoonan syndromeOsteogenesis imperfecta type IIPerlman syndromeRoberts syndromeShort-rib polydactily syndromeSmith-Lemli-Optiz syndromeSpinal muscular atrophy type 1Thanatophoric dysplasiaTrigonocephaly 'C' syndromeVACTEREL associationZellweger syndrome

THE 11-14 WEEK SCAN

I Fetal abnormalities

ABNORMAL NT NORMAL FETUS

Normally nuchal translucencydisappears by 14 weeks.

Noteworthy are cases with abnormal NT that resolve spontaneously around 14 weeks and show healthy outcome

Chromosomally and structurally normal fetuses with history of thickened NT with no evidence of nuchal fold thickening or non-immune hydrops, at 20 weeks -- no increased risk for perinatal or long-term morbidity and mortality

Chromosomally and structurally normal fetuses with

Altered dermal collagen composition (eg, Down syndrome)

Abnormal nuchal lymphogenesis (eg, Turner syndrome)

Hemodynamic alterations and cardiac dysfunction( heartdefects)

Abnormal endothelial cell differentiation

PATHOPHSIOLOGY OF NT-

NASAL BONE ABSENT PRESENT

MAXILLO FACIAL ANGLE NORMAL REDUCED INCREASED TRISOMY 21

DUCTUS VENOSUS FLOW reverse a wave a/w chromosomal

defects cardiac defects and adverse fetal outcome

TRICUSPID FLOW Prevalence of TCV regurgitation in fetuses with trisomy 21 is about

74% whereas only 7% of chromosomally normal fetuses have this finding There is an increased prevalence of cardiac defects with TC regurgitation, irrespective of the presence or absence of aneuploidy

FETAL MEASUREMENTS AS MARKERS FETAL GROWTH/ CRL - REDUCED GROWTH CAN BE SEEN IN

TRISOMY 13 ,18, TURNERS SYNDROME HOWEVER NOT IN TRISOMY 21

FETAL HEART RATE -BRADYCARDIA SEEN IN TRISOMY 18 AND TRIPLOIDY AND TACYCARDIA IN TRISOMY 13 AND TURNER SYNDROME

FETAL STRUCTURAL DEFECTS AS MARKERS

SINGLE UMBILICAL ARTERY/ TWO VESSEL CORD SEVEN FOLD INCRESED RISK FOR TRISOMY 18

MEGACYSTIS MEGACYSTIS LONG. BLADDER OF >7MM 7-15 MM A/W INCREASED RISK OF TRISOMY 13 AND 18 EUPLOID FETUSES –SPONTANEOUS RESOLUTION >15 MM LESS LIKELY CHROMOSOMAL ANOMALIES MORE LIKELY TO CAUSE OBSTRUTIVE UROPATHY

OMPHALOCOELE HIGH ASSOCIATION WITH TRISOMY 18 ONE OF THE REASONS TO PERFORM NT SCREENING AT

11WEEKS NO PHSIOLOGICAL BOWEL HERNIATION

OMPHALOCOELES WITH ONLY BOWEL HERNIATION STRONGER ASSO. WITH ANEUPLOIDY

Aneuploid fetuses with omphalocoeles containing only bowel show resolution in significant no of fetuses, most likely developmental delay.

HOLOPROSENCEPHALY EXTREME FORM ALOBAR HOLOPROSENCEPHALY CAN BE

DETECTED IN FIRST TRIMESTER INCREASED RISK OF ANEUPLOIDY MOSTLY TRISOMY 13

THE FIRST TRIMESTER ANOMALY SCAN DETECTABLE ABNORMALITIES

THE FIRST TRIMESTER SCAN IS NO LONGER A NT SCAN BUT A

FETAL ANATOMY SCAN

INTRACRANIALTRANSLUCENCYIN OPEN NEURAL TUBE DEFECTS

a case of open spina bifid demonstrating compression of the fourth ventricle with no visible translucency.

The fourth ventricle presents as an intracranial translucency (IT)between the brain stem and the choroid plexus.

ARNOLD CHIARI 2Lemon sign: Scalloping of frontal bonesBanana sign: Caudal displacement of cerebellum , obliteration of CMNot consistently seen in first trimester.

POSTERIOR FOSSA AT 11 TO 13.6 WEEKS NORMAL POST FOSSA CYST OPEN

SPINA B

NEURAL TUBE DEFECTS Meningoenc Occipital (MC) – A/w skull defect (cf D/D Nuchal cystic hygrom Parietal Frontoethmoidal

A/w Microcephaly, Hydrocephalus, Spina bifida, Meckel Gruber Syn.

d/d : Cystic Hygroma

ACRANIA–EXENCEPHALY-ANENCEPHALY

SKULL OSSIFICATION AT 11 WEEKS OF OCCIPITAL BONE

Varying degrees of distortion of brain

MECKEL GRUBER SYNDROME Encephalocoele Polycystic kidneys Polydactyly

DANDY WALKER COMPLEX Complete or partial absence of cerebellar vermis 4th Ventricle Dilatation End point of chromosomal abn. , Genetic

Syndromes , congenital infection or Isolated abn

HYDRANENCEPHALY Total absence of cerebral hemispheres

Large head Small hemispheres Fluid-filled intracranial cavity

with no midline echoes

HOLOPROSENCEPHALY Alobar and Semilobar a/w facial abnormalities Lobar

INIENCEPHALY Rare Cervical dysraphism with

occipital(inion) defect + encephalocoele

Persistently extended fetal head -clue

CARDIAC ANOMALIES Fetal 4 chamber view can be demonstrated at 11to 14 weeks

scan

RAISED NT PERSISTENT BRADYCARDIA (60BPM) COMPLETE AV CANAL DEFECT

A 14 WEEK SPECIALIST SCAN CAN REVEAL MAJOR ABN OR RAISE SUSPICION FOR LATER DETAILED SCAN

4 CHAMBER VIEW AV CANAL DEFECTS VSD

MUSCULOSKELETAL ABN. CAUDAL REGRESSION SYNDROME DEGREES OF VERTEBRAL ANOMALIES FROM PERTIAL SACRAL

AGENESIS TO ABCENCE OF LUMBAR SPINE. 250 TIMES MORE COMMON IN POORLY CONTROLLED DIABETIC

MOTHERS

ABSENT LIMBS

BODY WALL ANOMALIES PHSIOLOGIC BOWEL HERNIATION

AT 9 TO 11 WEEKS

EXOMPHALOS - a/w CHROMOSOMAL DEFECTS .CORD INSERTION AT APEX OF SAC VS GASTROCHISIS PARA MIDLINE HERNIA SAC

URINARY ANOMALIES PYELECTASIS RANGE

MEGACYSTIS CYSTIC DYSPLASTIC KIDNEY RENAL AGENESIS POLYCYSTIC KIDNEYS

SECOND TRIMESTER FETAL ANOMALY

CARDIOVASCULAR ANOMALY

Fetal cardiac examinations optimally performed between 18-22 weeks.

Some anomalies may be identified in late first and early second trimester especially when increased nuchal translucency is identified.

4 chamber view, 3 vessel view and outflow tracts can detect 80% -85% of cardiac anomalies

four chamber view

BASIC VIEW

Right ventricular outflow tract(RVOT)

Left ventricular outflow tract(LVOT)

EXTENDED BASIC VIEWS

VSD• One of the most common congenital cardiac anomaly• VSD is easily diagnosed on the four-chamber view

alone. • However, color Doppler US may be needed to

demonstrate smaller defects and some may not be detected until after birth.

Small VSD (MUSCULAR)show spontaneous closure

ENDOCARDIAL CUSHION DEFECT When the endocardial cushions fail to fuse, a

wide range of atrioventricular septal defects occur.

(four-chamber view)shows absence of the interventricular and interatrialsepta, thus producing connectionsbetween the ventricles and between the atria.

PERSISTENT TRUNCUS ARTERIOSUS The undivided truncus receives blood from

both ventricles. A VSD is almost always present

a.(four-chamber view) shows a VSD (arrow). Dao descending aorta. b.(base view)shows a single trunk (arrow) overriding both ventricles.

HYPOLPASTIC LEFT HEART SYNDROME Small left ventricle, which is associated

with aortic atresia. Atretic or hypoplastic mitral valve.

Hypoplastic left heart syndrome in a fetus(four-chamber view) shows that the left ventricle issmall relative to the right ventricle and the left atrium issmall relative to the right atrium.

EBSTEIN ANOMALY CAUDALLY PLACED TRICUSPID VALVE /OFFSET BETWEEN MITRAL AND

TRICUSPID VALVE /ENLARGED RT VENTRICLE /TRICUSPID REGURGITATION

DOUBLE OUTLET RIGHT VENTRICLE PARALLEL OUTFLOW TRACTS , LARGE RT VENTRICLE ,SMALL LT

VENTRICLE

RHYTHM AMNORMALITIES OF HEART NORMAL HEART RATE 2ND IS 120BPM TO 160BPM FETAL ARRYTHMIAS  can now be defined precisely for mechanism-

specific therapy and for subsequent monitoring of response.

MSK ANOMALIESFETAL SKELETAL STRUCTURES TO BE SEEN:FETAL CRANIUM(BPD, HC)ABDOMINAL CIRCUMFERENCE(AC)MANDIBLECLAVICLESCAPULACHEST CIRCUMFERENCEALL FETAL LONG BONES( RHIZOMELIA, MESOMELIA, MICROMELIA)FETAL FACIAL PROFILE(GLABELLAR BOSSING, FLATTENED NASAL BRIDGE, MICROGNATHIA)VERTEBRAL BODIESHAND AND FEET( EXTRA/MISSING/MALFORMED DIGITS)MINERALISATION PATTERN.CHEST:ABDOMEN CIRCUMFERENCE( <0.6 ABNORMAL)FL:AC RATIO(<0.16 ABNORMAL)FL: FOOT LENGTH RATIO(<1 ABNORMAL)

CONTD.. FETAL LONG BONES:

PRESENCE/CURVATURE/MINERALISATION/FRACTURES The femur length–abdominal circumference ratio (<0.16 suggests lung hypoplasia) femur length–foot length ratio(normal = 1, <1 suggests skeletal dysplasia) THORAX: CHEST CIRCUMFERENCE/ CT RATIO MEASURED AT THE

LEVEL OF FOUR CHAMBER VIEW OF HEART. HAND AND FEET: PRE AND POSTAXIAL

POLYDACTYLY/SYNDACTYLY/CLINODACTYLY/OTHER DEFORMITIES SKULL:HC/BPD/SHAPE/MINERALISATION/OSSIFICATION. FACIAL STRUCTURES:MICROGNATHIA/ SHORT UPPER LIP/ABNORMALLY

SHAPED EAR/FRONTAL BOSSING/CLOVERLEAF SKULL. PELVIS: HYPOPLASTIC ACETABULAE/FLAT ILIAC BONES.

FETAL SKELETAL DYSPLASIA LIMB DEFICIENCY: complete absence –

amelia, incomplete absence-meromelia.

lack of a normal hand and the abnormal soft tissue at the distal end of theforearm

THANATOPHORIC DYSPLASIA Disproportionate dwarfism with very short

extremities,which are bowed in type 1 and may be straight in type 2.

Thorax is narrow. Cloverleaf skull deformity is generally seen in type 2. Polyhydramnios is present in almost 50% of cases. Pulmonary hypoplasia.

telephone receiver–shapedfemur

hypoplastic thorax

OSTEOGENESIS IMPERFECTA Rib fractures Thin cortex in tubular bones, and, in more severe

cases thin shafts with fractures and bowing deformities.

The skull may be thinner than usual and the weight of the US probe may deform the head quite easily. In severe cases, the cranial vault has a wavy outline and is easily compressed.

OSTEOGENESIS IMPERFECTA

bone fractures anddeformities.

decreased skull ossification

irregularshape of the ribs a finding that also suggestsfractures.

CHONDRODYSPLASIA PUNCTATA

Craniofacial dysmorphismVery short humeri and relatively short femora Punctate calcification of epiphyses may be seen prenatally multiple contractures

DIASTROPHIC DYSPLASIA• diastrophic” implies twisting and describes the

twisted habitus in diastrophic dysplasia

short broad long bones bilateral clubfeet with limb shortening

bilateral clubfeet with limb shortening (arrowheads)and bilateral hitchhiker’s thumb (arrow)

?RACIAL VARIATION UNIFORMLY SMALL LONG BONES CASE OF SHORTENING OF LONG BONES MANIFESTED AFTER 20

WEEKS FEMUR FOOT RATIO .9 THORACIC CIRCUMFERENCE /AC AND CARDIAC THORAX

RATIOS

CONT

THORAX ABNORMALITIES Diaphragmatic hernia- Abdominal organs will be in the chest.

Fluid filled mass just behind the left atrium and ventricle.Suspicious if stomach not visualized in abdomen.shift in the mediastinumSmall abdominal circumferencePolyhydramnios

Peristalsis of bowel in fetal chest.

.

.

CCAM/ CPAM SOLID /CYSTIC/ MIXED MASS CAM can displace mediastinal structures with compression of

the heart and IVC.Generally unilateral involving a single lobe.Associated with Hydrops,polyhydramnios,

and pulmonary hypoplasia. Many times small with little mass effect

PULMONARY SEQUESTRIAN Well circumscribed,uniformly echogenic mass in the fetal thorax. May be associated with fetal hydrops and maternal polyhydramnios. Color-Doppler todetect the arterial supply from the descending aorta to the mass.d/d CCAM

TRACHEAL/ LARENGEAL ATRESIA

If trachea or larnx is partially or completely obstructed, fluid is secreted by the lungs cannot be expelled. So distended lung, appears hyperechogenic and bronchi become dilated. Associated with fetal ascites.

Echogenic Bowel

ECHOGENIC BOWEL To call it echogenic bowel the echogenicity should be equal to bone.IN THIRD TRIMESTER ECHOGENIC IS NORMAL AS MECONIUM IS ECHOGENIC50% CASES OF ISOLATED ECHOGENIC BOWEL RESOLVE OVER TIME

Truly echogenic bowel in a second-trimester fetus, differential diagnostic considerations include Cystic fibrosis Chromosomal abnormalities-look for morphological anomalies ,congenital infection and intraamniotic bleeding, a/w IUGR

MECONIUM PERITONITIS

ECHOGENIC GASTRIC DUPLICATION CYST

1/3RD CASES A/W OTHER ABNORMALITIES GI and SPINAL

FETAL MASSES

NEUROBLASTOMA Associated malformations are unusual. Neuroblastoma is

characteristically a heterogeneous solid mass with cystic components that displaces the adjacent kidney inferiorly and

laterally. . Spontaneous regression occurs in up to 40% of cases.

SUBDIAPHRAGMATIC EXTRALOBAR PULMONARY SEQUESTRATION

MESOBLASTIC NEPHROMA Arteriovenous shunting, Heart failure and Polyhydramnios are

common. Mesoblastic nephroma is benign, and postnatal nephrectomy is curative

CARDIAC MASSES MC RHABDOMYOMA A/W TUBEROUS SCLEROSIS

TERATOMAS SACROCOCCYGEAL TERATOMAS – MC .HIGHLY VASCULAR

RESULTANT VASCULAR STEAL CAUSES HYDROPS/ POLYHYDAMNIOS AND PRE MATURE DELIVERY

NECK TERATOMAS

FETAL GENITOURINARY ABN

ABNORMALITIES PRESENTING IN THIRD TRIMESTER

OESOPHAGEAL ATRESIA Prenatally, the diagnosis of esophageal atresia is suspected

when, in the presence of polyhydramnios (usually after 25 weeks), repeated ultrasonographic examinations fail to demonstrate the fetal stomach.

SMALL BOWEL OBSTRUCTION The lumens of the small bowel and colon do not normally

exceed 7 mm and 20 mm, respectively. Diagnosis of obstruction is usually made quite late in pregnancy (after 25 weeks), as dilatation of the intestinal lumen is slow and progressive. Jejunal and ileal obstructions are imaged as multiple fluid-filled loops of bowel in the abdomen.

OVARIAN CYSTS  Fetal ovarian cysts are hormone-sensitive (human chorionic

gonadotropin from the pLacenta) and tend to occur after 25 weeks of gestation

cysts are benign and resolve spontaneously in the neonatal period

FUTURE DIRECTIONS

SCREENING AT 6 TO 10 WEEKS CRL GSD YSD FHR RECENT PAPER BY FMF HAS SHOWN A sonographically

detectable differences between euploid and trisomic embryos.