Plausible explanations for the detection of false positive results in NIPT of fetal aneuploidies are which of the following?

• a)
  

  Low fetal DNA fractions

  
  
• b)
  

  Confined placental mosaicism

  
  
• c)
  

  An increased maternal weight

  
  
• d)
  

  Presence of a tumor in the mother

  
  
• e)
  

  Presence of vanishing twins in pregnancy

In which scenarios would the use of an exclusionary approach, analyzing a paternally inherited allele in maternal plasma, be clinically significant?

• a)
  

  Pregnancy where the mother is affected by an autosomal dominant disease

  
  
• b)
  

  Pregnancy in couples sharing the same mutations for an autosomal recessive disease

  
  
• c)
  

  Pregnancy in couples being carriers of different mutations for an autosomal recessive disease

  
  
• d)
  

  Pregnancy where the mother is affected by an X-linked recessive disease

  
  
• e)
  

  Pregnancy where the father is affected by an X-linked recessive disease

The following statement(s) is/are true about the relative haplotype dosage (RHDO) approach?

• a)
  

  The RHDO analysis is more conveniently performed using DNA information obtained from the dPCR rather than sequencing analysis of maternal plasma

  
  
• b)
  

  The RHDO analysis enables one to identify maternally inherited mutations in maternal plasma

  
  
• c)
  

  The RHDO analysis can be used for the detection of paternally inherited mutations

  
  
• d)
  

  The informative SNPs for deducing the maternal inheritance are heterozygous in the father and homozygous in the mother

  
  
• e)
  

  The RHDO analysis could be performed on targeted sequencing data

The following statement(s) is/are true about the NIPT of thalassaemia?

• a)
  

  The exclusionary approach based on the lack of detection of the thalassaemia mutation enables one to distinguish between thalassaemia major and thalassaemia minor

  
  
• b)
  

  Several enrichment strategies, such as a size-based fractionation, PNA-clamp PCR, PIRA-PCR, full COLD-PCR have been developed for the detection of fetal thalassaemia mutations

  
  
• c)
  

  The agarose gel-based size fractionation has been shown to be the most successful method for the enrichment of fetal mutations from maternal plasma by physically selecting fetal DNA fragments, which are longer in size as compared to maternal DNA

  
  
• d)
  

  The targeted sequencing approach is a robust and powerful method for the analysis of monogenic diseases using plasma cell free DNA

  
  
• e)
  

  NIPT of monogenic diseases is currently a cost-effective strategy in prenatal testing

What are the main technical challenges associated with deriving an accurate genotype when using amplification-based PGD analysis on (usually) single embryo cells?

• a)
  

  Complete amplification failure

  
  
• b)
  

  Contamination with foreign DNA

  
  
• c)
  

  Whole genome amplification

  
  
• d)
  

  The time-limit if embryos are to be transferred in a fresh cycle

  
  
• e)
  

  Allele-drop out.

A 25 year old Asian woman presents at 31 weeks gestation with three-plus oedema and the symphysio-fundal height measuring 38cm. A diagnosis of hydrops fetalis with maternal mirror syndrome is considered. Which of the following would be appropriate clinical actions?

• a)
  

  A complete blood count should be taken

  
  
• b)
  

  An obstetric ultrasound should be performed

  
  
• c)
  

  A complete workup for pre-eclampsia including coagulation profile should be performed

  
  
• d)
  

  Vaginal delivery should be allowed if the subsequent presentation is cephalic

  
  
• e)
  

  Prophylaxis for postpartum hemorrhage should be undertaken at delivery

A 30 year old Chinese nulliparous woman was found to have anaemia with a hemoglobin level of 9.0 g/dl at routine antenatal screening at 10 weeks gestation. Which of the following would be appropriate clinical actions?

• a)
  

  She should be prescribed iron supplementation

  
  
• b)
  

  A complete blood count should be performed

  
  
• c)
  

  A complete blood count should be taken from her partner if her MCV is 78 fL

  
  
• d)
  

  Her fetus could have a neural tube defect if the couple have both microcytosis and hypochromia

  
  
• e)
  

  She should be prescribed folic acid

A 39 year old woman with Thalassaemia Major consults for antenatal care of her IVF pregnancy at 8 weeks gestation. She has had a splenectomy performed last year and her frequency of transfusion is markedly reduced. Which of the following would be appropriate clinical actions?

• a)
  

  Prenatal diagnosis should be arranged

  
  
• b)
  

  Chelation therapy should be discontinued

  
  
• c)
  

  She should see a cardiologist for assessment of her cardiac status

  
  
• d)
  

  Her risk of thromboembolic complications is much reduced following splenectomy

  
  
• e)
  

  There is no need to screen for infections since she is receiving less frequent transfusions

You are providing shared care with a family physician for a 35 year old Chinese woman confirmed to have Hb H disease. She is now at 28 weeks gestation and fetal growth has been satisfactory. You should do which of the following?

• a)
  

  Monitor her complete blood count at regular intervals until delivery

  
  
• b)
  

  See her again at 36 weeks gestation

  
  
• c)
  

  Arrange an oral glucose tolerance test to rule out gestational diabetes mellitus even though there is no relevant family history

  
  
• d)
  

  Admit her for assessment and monitoring if she complains of continuous back pain and abdominal cramps

  
  
• e)
  

  Arrange for an elective cesarean delivery at 38 weeks gestation

The following statement(s) is/are true about maternal cell contamination (MCC)?

• a)
  

  The chance of MCC can be reduced by discarding the first 2 ml of sample withdrawal in amniocentesis.

  
  
• b)
  

  Culture of the amniotic fluid can decrease the risk of MCC.

  
  
• c)
  

  CVS culture can decrease the risk of MCC.

  
  
• d)
  

  MCC can be excluded if it had no evidence of visible blood staining in amniotic fluid.

  
  
• e)
  

  Testing maternal contamination is necessary in molecular prenatal diagnosis.

The following statement(s) is/are true about ultrasound in the prenatal diagnosis of thalassemia?

• a)
  

  Ultrasound can detect homozygous α-thalassemia.

  
  
• b)
  

  Ultrasound can detect homozygous β-thalassemia.

  
  
• c)
  

  Invasive procedures are not necessary if ultrasound detects a hydropic fetus.

  
  
• d)
  

  For a couple at risk for α-thalassemia, the pregnancy will have no chance of being complicated by fetal hydrops if homozygous α-thalassemia has been excluded by invasive testing at early gestation.

  
  
• e)
  

  In skilled hands, homozygous α-thalassemia can be detected by ultrasound in the first trimester.

The majority of fetuses affected by homozygous α ⁰ -thalassemia show the following abnormal ultrasonographic features in the first trimester?

• a)
  

  Fetal cardiomegaly at 11 weeks

  
  
• b)
  

  Placentomegaly

  
  
• c)
  

  Increased middle cerebral artery peak systolic velocity >1.5 multiple of medians

  
  
• d)
  

  Nuchal translucency ≥ 3.5mm

  
  
• e)
  

  Hydrops

The majority of the fetuses affected by homozygous α ⁰ -thalassemia show the following abnormal ultrasonographic features in the second trimester?

• a)
  

  Fetal cardiomegaly

  
  
• b)
  

  Placentomegaly

  
  
• c)
  

  Increased middle cerebral artery peak systolic velocity >1.5 multiple of medians

  
  
• d)
  

  Hydrops

  
  
• e)
  

  Limb reduction

Compared to Rhesus iso-immunisation, using middle cerebral artery peak systolic velocity to predict fetuses affected by homozygous α ⁰ -thalassemia is less optimal because of which of the following reasons?

• a)
  

  The anaemia in an affected fetus can be mild

  
  
• b)
  

  The blood viscosity of the majority of the affected fetuses is high

  
  
• c)
  

  The physical properties of haemoglobin Bart’s may differ from haemoglobin F

  
  
• d)
  

  It is difficult to accurately measure middle cerebral artery peak systolic velocity in the first trimester

  
  
• e)
  

  There is a lot of overlap in the measurements between affected and unaffected pregnancies.

Fetal cardiomegaly can be due to which of the following disorders other than homozygous α ⁰ -thalassemia?

• a)
  

  Alpha thalassemia trait

  
  
• b)
  

  Haemoglobin H disease

  
  
• c)
  

  Congenital heart disease

  
  
• d)
  

  Fetal growth restriction

  
  
• e)
  

  Homozygous beta thalassemia

The following is/are indicative of a typical β -thalassaemia carrier:

• a)
  

  HbA ₂ level <3.5%

  
  
• b)
  

  Microcytosis

  
  
• c)
  

  HbF level >10%

  
  
• d)
  

  HbA ₂ level >3.5%

  
  
• e)
  

  Hypochromia

A 17 years old women visits a clinic for a general check-up. She complains of irregular menstruation and feeling fatigue for several days. Her peripheral blood tests are indicative of mild anaemia, and microscopic analysis of the blood smear is reported to be hypochromic and microcytic. Her blood test results are presented below for reference.