Ultrasound markers of chromosomal abnormalities Prof. Z. Babay

General Facts: The general incidence of Down is 1:1000 The risk by maternal age: at the age of 35 -----------1:365 at the age of 40-----------1:109 at the age of 45-----------1:32 Risk of recurrence is 1% ( 0.75% higher than maternal age related risk ** In case of parental aneuploidy---- 30% risk of Trisomy in offspring

Methods available for screening Maternal age Biochemical---1st trimester---PAPPA&β HCG, Adam12 2nd trimester---Triple & quadriple Test Ultrasound NT + Other markers Fetal DNA

Sensitivity of screening False Positive Rate 5% Detection rate 61% for Down 63% for Trisomy 18 1st trimester (Biochemical) <5% for Down <1% for Trisomy 18 70% for Down 80% for Trisomy 18 2nd trimester (Biochemical) 10% 33% Age alone 8% 82% for Down 78% for Trisomies Ultrasound NT

First trimester markers: Fetal growth: CRL< 7mm indicate 3 times higher risk of Chromosomal abnormality Fetal heart rate: Normal is 100 beats/min at 6 weeks 160-170 beats /min at 9 weeks A significant increase in heart rate is seen in trisomies

Fetal structural malformations: 11-14 weeks Holoprosencephaly: 3% of trisomy 18 39% of trisomy 13 Facial clefts: 1% of trisomy 21 10% of trisomy 18 2% of triploidy

Central cleft palate & lip

Fetal Structural malformations: Micrognathia: 1% of trisomy 21 53% of trisomy 18 9% of trisomy 13 44% of triploidy Cystic Hygroma: 88% of Turners

Fetal Structural malformations: Chest & cardiac malformations: 26% of trisomy 21 52% of trisomy 18 43% of trisomy 13 48% of turners 16% of triploidy

Fetal structural malformations: Malformations of the abdomen: Exomphalos 31% of trisomy 18 17% of trisomy 13 Nasal bone hypoplasia at 15-24 weeks (<2.5 mm): 2/3 of trisomy 21 If combined with N.T. –90% sensitivity 3% false positive

Fetal Structural abnormality: Megacystis: Normally the bladder is seen at 10-14 weeks Megacystis if longitudinal diameter is 6-8mm or bladder / CRL ratio is 13% or more It resolve in 60% of cases 20% risk of chromosomal abnormality

Megacystis

N.T. Skin fold thickness behind the fetal cervical spine Due to Venous or lymphatic engorgement Landmarks: Cavum septum pellucidum, Cerebral peduncles, Cerebellar hemispheres Timing: 11-13 +6days weeks of pregnancy

N.T. Continuation Risk estimate: 3 mm----3 times the incidence by maternal age 4mm----18 times 5mm----28times 6mm----36times

Measurement of N.T. CRL between 45-84mm Good sagital section Fetal head lines with the spine Enlarge the view Measure the widest part of the thickness

Measurement of N.T. (cont.) Measure from the inner border of the horizontal line of the calliper placed on the line that defines the N.T. thickness

Cont. The gain should be low in the magnified image Distinguish between fetal skin & amnion Take more than one measurement

N.T.

N.T.

N.T.

N.T. 75-80% of trisomy 21 5-10% normal karyotype ( but could be associated with cardiac defects, diaphragmatic hernia, Exomphalos) If NT is abnormal ---indicate fetal ecchocardiogram

Fetal Structural malformation: Umbilical cord diameter: At 10-14 weeks Increase in diameter above the 95th centile is associated with abnormal karyotype

Umbilical cord pulsatility index: Trisomy fetus show small muscular artery/villi ratio UAPI increase in trisomy (controversial)

Ductus venosus velocimetry: Absence of or inversion of ductus venosus atrial (ACV)---- 70-90% of abnormal karyotype

Second trimester markers: Nuchal fold: Cut off 5mm---at 14- 18 weeks 6 mm--- at 18-20 weeks The most sensitive and specific marker in the second trimester Sensitivity 77.8% False positive rate 2%

Nuchal fold

BPD/FL BPD/FL ratio Its value varies with gestational age PPV= 1/294 for general population PPV= 1/112 for maternal age >35 1.5 S.D. above the mean of BPD/FL Sensitivity 50% False positive 7%

Humerus length: Measured to expected length <0.9 50% sensitivity 6.2% false positive

Pyelectasis: Found in 1% of fetuses Mild--A-P diameter of renal pelvis >4mm at 15-19 weeks A-P diameter of renal pelvis >5mm at 20-29 weeks A-P diameter of renal pelvis > 7mm at 30-40 weeks Moderate-- > A-P diameter of renal pelvis >10 mm + pelvi-calyceal dilatation

Pyelectasis: 17% incidence of Down 2% false positive rate In severe hydronephrosis, multicystic kidneys, renal agenesis---risk of trisomy 18 &13

Echogenic intra-cardiac focus: 18% incidence of Down 2 fold increase over the age based risk More significant if Right ventricle is involved

Choroid Plexus cyst: Present in 1/3 of trisomy 18 present in 1-2% of normal fetuses If isolated the risk is 1/374 If an additional abnormality is found the risk increase 20 folds

Choroid plexus cyst

Echogenic bowel(compared to surrounding bone) Risk of abnormality is 0.5-1% Also seen in meconium ileus, congenital infection, severe IUGR, intra-amniotic bleeding, cystic fibrosis Increase the risk by 3-5 times the maternal age risk

Short proximal bones Syndactaly is associated with Triploidy Sandal gap with Trisomy 21 Polydactaly with Trisomy 13 Overlapping fingers, Rocker bottom feet and talipes with trisomy 18

Simian crease

Trisomy 18

Double pubble 30-40% risk of aneuploidy ( trisomy 13& 18)

Minor markers: Wide iliac crest angle >90 degree Brachycephaly Frontal lobe shortening Abnormal short ear length Flat face Clinodactaly Hypo-plasia of middle phalanx of the 5th digit Sandal gap of great toe Simian crease Small cerebellar diameter

Wide iliac crest

Mild Ventricolomegaly (10-12 mm) 5% risk of later severe brain abnormality 15% risk of mild problems later The commonest abnormality is trisomy 21, 18, 13 & Triploidy

Echogenic intra-cardiac focus Combination of markers: Score of > 2 ----–81% detection rate & 4.4% false +ve Score of 0----- risk is 1.5/1000 Score Findings 2 Major anomaly Nuchal fold> 6 mm 1 Short femur Short humerus Pylectasis > 4mm Hyper-Echoic bowel Echogenic intra-cardiac focus

Absence of any markers conveys 70% reduction in Down Syndrome

Final remarks: Detection by ultrasound depend on personal experience Proper timing of scan

Good Day