Introduction

What is Triploidy?

A healthy adult human body is made up of approximately 28 to 36 trillion cells.¹ Information needed for the formation and functioning of the body that makes each of us unique, is stored in genes as different DNA patterns. Genes in turn are arranged together in thread-like structures called chromosomes which are contained in the nucleus of each cell.²

Normal human somatic cells (those except for germ cells - i.e. sperms and eggs) contain 46 chromosomes as 23 pairs, one copy of the pair received from the mother and the other copy from the father.² In triploidy there are 3 copies of each pair of chromosomes and thus 69 chromosomes in total. It is a rare condition affecting around 1% of pregnancies.³

Triploidy commonly results in miscarriage, early infant death and a number of congenital anomalies.⁴ Therefore, it is important to diagnose triploidies during pregnancy for optimum antenatal management and provision of support and guidance for parents and caretakers. 

The genetics of Triploidy

During fertilisation the sperm and the egg contribute by one set of chromosomes (haploid cells with unpaired 23 chromosomes) each to form the diploid zygote (with 46 chromosomes). In triploidy an additional set of chromosomes is received from the maternal or paternal side.³ 

This can occur in three ways:⁴

• Fertilization of an egg by two sperm
• Fertilization of an egg by a sperm with an extra set of chromosomes
• Fertilization of an egg with extra set of chromosomes by a sperm

The egg or the sperm can have an additional copy of chromosomes if an error in division (meiosis) occurs during germ cell production.

According to the origin of the extra set of chromosomes, triploidy can be divided into:⁵

• Digynic triploidy (69 XXX) – extra set of chromosomes from mother
• Diandric triploidy (69 XXY or 69 XYY) - extra set of chromosomes from mother

Clinical presentation of Triploidy

Triploidy results in changes in both the placenta and the foetus, which manifest in different organ systems.⁶

Clinical features of the foetus & newborn:

• Growth restriction 
• Facial deformities such as wide spaced eyes, low nasal bridge, low set ears, cleft lip and palate
• Enlarged head (macrocephaly)
• Fused fingers and toes
• Heart defects such as Atrial Septal Defects, Ventricular Septal Defects and Tetralogy of Fallot
• Cystic kidneys
• Twisted intestines
• Abnormal development of the brain and seizures
• Intellectual disability
• Genital defects
• Defects in adrenal and thyroid glands

Clinical features of the placenta and mother:

• Large placenta with multiple cysts
• Features of preeclampsia including high blood pressure, swelling of the body and passage or protein in urine

Generally these clinical manifestations will depend on whether the triploidy is digynic or diandric⁴:

• Type 1 - normal sized fetus with small head and large cystic placenta is associated with diandry (paternal origin)
• Type 2 - growth restricted fetus with a large head and non-cystic placenta is associate with digyny (maternal origin)

Outcomes of a Triploid pregnancy

Most triploid foetuses are spontaneously miscarried between the 7th and 17th week of gestation.⁴ Rarely, the foetus might survive the full term of pregnancy and the newborn would have severe birth anomalies incompatible with life, resulting in death in a few hours to days or weeks. 

Generally, digynic triploid foetuses tend to survive longer durations compared to diandric triploid foetuses.⁴

Diagnosis of Triploidy

Changes in the foetus and placenta in triploidy can be detected via screening tests which include ultrasound scanning, biochemical testing and detection of circulating foetal DNA via non-invasive prenatal testing.⁴ Once these tests show abnormal results, confirmation can be done via karyotyping using cells obtained by amniocentesis or chorionic villus sampling.⁴ These are classified as diagnostic tests.

Screening tests for Triploidy

Various screening tests exist for triploidy, however they can only provide a risk estimate of triploidy of the foetus, and not a confirmed diagnosis.⁷ However, these tests are easy to perform and safe for the foetus and mother.

Ultrasound scan (USS)

Features of triploidy vary considerably as some foetuses show notable abnormalities while others seem normal⁵.

Common features of triploidy seen on USS include:³

• Intrauterine growth restriction
• Macrocephaly (enlarged head) 
• Hydrocephalus (build up of fluid within the brain)
• Reduced amniotic fluid (Oligohydramnios)
• Abnormally large placenta (in diandric triploidy)
• Fused 3rd and 4th fingers (syndactyly)

Biochemical tests

Abnormalities in the levels of certain biomarkers in maternal blood are used to screen for triploidy.⁴

Alpha-fetoprotein (AFP)

• Decreased in digynic triploidy
• Increased in diandric triploidy

Human beta chorionic gonadotropin (hCG)

• Decreased in digynic triploidy
• Increased in diandric triploidy

Pregnancy-associated plasma protein A (PAPP-A)

• Decreased in both digynic and diandric triploidy

Unconjugated estriol

• Decreased in digynic triploidy

Non-invasive prenatal test

Foetal cells enter maternal circulation frequently across the placenta and by the second trimester there is approximately one foetal cell per 10,000 to 1 million maternal cells in blood. Breakage of these cells in the mother’s blood leads to formation of cell free DNA (cfDNA) which can be found in a concentration 25 times higher than the foetal cells.⁸ These DNA fragments can be used in the detection of the extra set of chromosomes in triploidy.⁹

Diagnostic tests for Triploidy

There are also tests that can confirm the presence of triploidy by direct analysis of chromosomes derived from foetal cells, but are more invasive and carry higher rates of complications for the foetus and the mother.⁷

Chorionic villus sampling (CVS)

This is usually performed between 11 and 14 weeks of gestation.¹⁰ A needle is inserted under ultrasound guidance through the vagina or abdomen, and a small piece from the finger-like projections of placenta (chorionic villus) is taken for analysis.

CVS carries a risk of miscarriage (around 1 to 2%),¹¹ bleeding, infection, limb deformities, and leakage of amniotic fluid due to rupture of membranes.¹² 

Amniocentesis 

Amniocentesis is usually done after 15 weeks of gestation.¹⁰ It involves insertion of a thin needle through the abdomen under ultrasound guidance to collect a small amount of amniotic fluid (liquid substance surrounding the fetus) which contains shedded foetal cells. The risk for miscarriage after amniocentesis is around 1%.¹¹ Other potential complications include infection, amniotic fluid leakage, foetal injuries, and increased risk of preterm labour.¹³

Management of a Triploid pregnancy

Triploidy is incompatible with life and most foetuses miscarry spontaneously. Therefore, treatment is aimed at providing counselling and psychological support for the parents and family during the pregnancy and afterwards, as this will be a difficult and painful time period.¹⁴

If the baby survives the pregnancy, the goal of the healthcare team would be to minimise the discomfort of the baby (i.e. provide palliative care).¹⁴ Medications and supportive devices will be used to help the baby with the symptoms and complications. 

Once the baby is diagnosed with triploidy in early pregnancy, some may decide to terminate the pregnancy by medical or surgical methods.¹⁴ Medical termination can be done by using medicines such as mifepristone and misoprostol. Surgical termination is usually done via suction curettage or dilation and evacuation.

Genetic counselling will be provided to the parents and family to better understand the condition and take decisions on the future pregnancies.

FAQs

What are the reasons for the genetic alterations in triploidy?

Triploidy occurs sporadically and randomly without any specific cause. It is not a result of anything the parents have done before or during the pregnancy that could have been prevented. There is no association with a positive family history or mother’s age.

Can triploidy recur in a subsequent pregnancy?

As triploidy occurs randomly, it is a one-off event. The chance of a triploid pregnancy happening again is not higher than it happening the first time.

What is the difference between triploidy and trisomy?

Both triploidy and trisomy are genetic conditions. In trisomy there is an additional copy of one chromosome (compared to an additional copy of all 23 chromosomes in triploidy). Therefore, in trisomy there are a total of 47 chromosomes whereas in triploidy it is 69. Common conditions that occur as a result of trisomy are Down’s syndrome (trisomy 21), Edwards’ syndrome (trisomy 18), Patau’s syndrome (trisomy 13) and Klinefelter syndrome (XXY).

Summary

• Triploidy is a rare genetic condition resulting from the presence of an extra set of chromosomes.
• Majority of triploid pregnancies end up in spontaneous miscarriages or still births
• A baby with triploidy, if born, would have severe congenital anomalies incompatible with life and will only survive for a few hours to days
• Screening for triploidy can be done through ultrasound scanning, biochemical testing of maternal blood and detection of fetal DNA by non-invasive prenatal testing
• Diagnosis can be confirmed by chorionic villus sampling or amniocentesis, although these carry higher risks
• The mainstay of management is counselling and provision of psychological support to the family