NIPD for fetal sex determination

A guide for patients and healthcare professionals

How can NIPD determine fetal sex?

We know that there is a small amount of the baby’s DNA in the mother’s blood. NIPD looks for the presence of Y chromosome DNA sequences in the blood sample.  If Y chromosome material is detected, the fetus is male.

View the video below to see Stephanie Allen, clinical scientist at Birmingham Women’s Hospital, describe how the test works.

Why would NIPD for fetal sex determination be needed?

NIPD for fetal sex determination would be offered to couples if:

  • The mother is a carrier of an altered gene for a serious X-linked condition – view this video animation explaining X-linked inheritance.
  • Both parents are carriers of alterations for congenital adrenal hyperplasia (CAH). CAH is an autosomal recessive condition – view this video animation explaining autosomal recessive inheritance.

Usually women at high risk of these conditions will already be known to their local genetics department. However, if you suspect that a pregnancy is at increased risk and the family has not been reviewed by a geneticist, it is best to seek advice from your local genetics centre as soon as possible.

The British Society for Genetic Medicine and Genetic Alliance UK have a list of local genetics centres.

‘If the family has not been seen by a geneticist, seek advice from your local genetics centre’

How does NIPD for fetal sex determination work?

Maternal blood is tested for the presence of Y chromosome DNA.

If Y chromosome DNA is detected, the fetus is male.  If Y chromosome DNA is not detected, the fetus is female.

NIPD for fetal sex determination is 99.5% accurate.

Who is eligible for fetal sex determination NIPD?

Read through the following scenarios where the eligibility of NIPD would be considered.

stylised-patientFrom the patient’s perspective:

“I mentioned to my midwife that my sister had just had a child with Duchenne muscular dystrophy”

Duchenne muscular dystrophy (DMD) is an X-linked single gene disorder, which means a male fetus has a 50% chance of inheriting the condition from the mother. However, in this instance the woman would first need to have a genetic test herself to determine if she is a carrier of DMD. If the woman was found to be a carrier of DMD, then NIPD could be offered to determine the fetal sex. If NIPD shows the fetus is female, an invasive test may not be warranted, as females are not generally affected with the condition as they have two copies of the X chromosome.  If NIPD shows the fetus is male, there is a 50% chance that it will inherit the condition, so an invasive test for DMD can be performed to determine if the male fetus is affected.

“My partner has haemophilia”

Haemophilia is an X-linked single gene disorder where fetal sex determination is used to inform management of the delivery. However, it may therefore be more appropriate to determine fetal sex by 20-week anomaly scan than by NIPD. In this instance, a male fetus has a 50% chance of being affected with haemophilia.  During delivery, the use of vacuum extraction and certain instruments such as fetal scalp monitors should be avoided due to the risk of bleeding, and there should be a lower threshold for consideration of Caesarean section.

stylised-midwifeFrom the healthcare professional’s perspective:

 “My patient has a child with adrenoleukodystrophy and is a carrier herself”

Adrenoleukodystrophy is an X-linked single gene disorder, which means a male fetus has a 50% chance of inheriting the condition from the mother. If NIPD shows the fetus is male, an invasive test for adrenoleukodystrophy can be performed to determine if he is affected. If NIPD shows the fetus is female, an invasive test may not be warranted, as females are not generally affected with the condition as they have two copies of the X chromosome.

“My patient and her partner are both carriers for congenital adrenal hyperplasia”

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder where fetal sex determination informs the management of the pregnancy. If a pregnancy is at risk of CAH, the fetus can be treated with dexamethasone from 6 to 7 weeks’ gestation to prevent the abnormal development of external genitalia (virilisation) in a female fetus.  Dexamethasone treatment can then be discontinued if NIPD shows the fetus is male.

‘NIPD for fetal sex determination is 99.5% accurate’

What needs to be done?

Pregnancy dates must be confirmed by ultrasound scan. The scan should look carefully for multiple pregnancies and empty gestational sacs.

Testing for fetal sex determination is reliable from 7 weeks’ gestation, but different laboratories have different testing criteria. Before taking blood for fetal sex determination, it is important that you contact the genetics unit performing the laboratory analysis to make the relevant arrangements for taking and delivering the blood to them. You should also make sure you discuss how the patient will receive the results.

For information about NIPD for fetal sex determination offered at the North East Thames Regional Genetics laboratory at Great Ormond Street Hospital (GOSH), see our factsheet. To request a test from GOSH, download this form.

Samples should be sent to arrive in the laboratory within 24 hours of sampling if possible.

Please click here to see a list of laboratories offering NIPD for sex determination.

‘Testing for fetal sex determination is reliable from 7 weeks’ gestation, but laboratories have different criteria’

What results can be given?

Male fetus: Y chromosome DNA detected in the blood sample indicates the fetus is male. In the case of a serious X-linked condition, this will mean that there is a 50% chance that the fetus is affected by the condition and an invasive testing will be offered. In pregnancies at risk of CAH, if a male fetus is identified there is no need for dexamethasone treatment, but if parents want a definitive diagnosis, invasive testing will still be required.

Female fetus: The child will not be affected by the X-linked condition and so standard antenatal care will be given. In pregnancies at risk of CAH, where parents have requested antenatal treatment, this will need to be continued and invasive testing will be required for definitive diagnosis.

Inconclusive: This result occurs when there is not enough fetal DNA in the sample to provide an accurate result.

View the video below of Stephanie Allen explaining inconclusive results in more detail.

What happens with an inconclusive result?

A repeat NIPD can be offered, as the amount of cell-free fetal DNA increases throughout the pregnancy. An invasive test could also be offered. Parents can await the 20-week scan when sex can be accurately determined. Alternatively, they can be referred to a fetal medicine unit for fetal sex determination by ultrasound, which is reliable in expert hands after 12 weeks’ gestation.

‘Results will be given by a genetic counsellor, midwife or other healthcare professional’

How are the results given?

The way in which results are given is usually discussed before the test is carried out.

Results are typically returned within one week and will be given to the woman by a genetic counsellor, midwife or other healthcare professional so that the appropriate ongoing care can be planned.