Prenatal ultrasound prediction of homozygous α⁰-thalassemia

Abstract

Homozygous α0-thalassemia is a serious autosomal recessive disorder with

poor fetal outcome and severe maternal complications. Conventionally, prenatal

diagnosis is performed by an invasive test. A non-invasive approach using serial

ultrasonography can effectively reduce the need for invasive tests in unaffected

pregnancies.

For two-dimensional ultrasound prediction, a total of 777 at-risk fetuses were

studied from 12 to 20 weeks between 1995 and 2006. At 12–15 weeks’ gestation, the

highest sensitivity (98.3%) was achieved by the combination of fetal cardiothoracic

ratio (CTR) and/or middle cerebral artery peak systolic velocity (MCA-PSV) at a

false-positive rate of 15.8%. At 16–20 weeks’ gestation, the sensitivity of CTR was

100.0%, but the false-positive rate was 5.2%. In contrast, the false-positive rate of

MCA-PSV alone was 1.4% and that of the combination of CTR and MCA-PSV was

0%, although their sensitivities were less than 65%.

In a cross-sectional retrospective study of 546 samples at-risk and control (268

fetal and 278 neonatal cord blood), the degree of anemia was only mild in 27.5% of

the affected fetuses (see chapter 3 for definition of mild anemia). Because MCA-PSV

is not very predictive of mild anemia, this may be one of the reasons why MCA-PSV

is not very sensitive in predicting an affected pregnancy.

A total of 832 at-risk pregnancies were studied using same noninvasive approach

at Maternal and Neonatal Hospital of Guangzhou (MNH) and Tsan Yuk Hospital

(TYH). The overall sensitivity and specificity of the noninvasive approach was 100%

and 95.6% respectively. At MNH, the need for an invasive test was reduced by 78.6%,

and all the affected pregnancies were diagnosed before 24 weeks’ gestation. After

adequate training and monitoring the quality of the subsequent ultrasound

examinations, the results achieved at MNH were comparable to TYH, with at-risk

pregnancies including the affected ones being seen at a more advanced gestation at

MNH.

In a retrospective review of 361 women at risk of carrying an affected fetus, 311

(86.2%) opted for the non-invasive approach using CTR and/or placenta. The cost

saving of this non-invasive approach was relatively small (HK$ 2,651) in comparison

to the cost of the whole prenatal screening program. On the other hand, the

non-invasive approach was more expensive than the direct invasive approach for low

MCV couples, as well as couples discordant for α-thalassemia and β-thalassemia.

ages. These results support the adoption of non-invasive approach in which routine

invasive test or karyotyping is no longer performed.

A total of 106 at-risk pregnancies and normal controls were prospectively studied

using three-dimensional ultrasonography. Placental volume (PV) at 11-14 weeks, and

PV/CRL quotient at 9-14 weeks’ gestation of affected pregnancies were significantly

greater than unaffected pregnancies (P<0.05). Using a cut-off point of 1.2ml/mm for

PV/CRL quotient to predict an affected pregnancy, the sensitivity, and specificity was

96.2%, and 100.0% respectively.