Why we don't know what causes most birth defects

The development of a baby, from the time of fertilisation through to the moment of birth, is an incredibly complex journey. Most of the time the result is a perfect new baby. However, in about 3% of babies mistakes happen and a birth defect occurs. This is when an anatomical difference has come about as the baby develops in the womb.

Birth defects (also known as congenital anomalies) are a major cause of infant hospitalisation and deaths in the first year of life. These are not only costly to manage in the health-care system, but can also have an enormous impact on the lives of the child and their family.

Some birth defects are relatively mild, can be repaired with simple surgery and the child will go on to lead a perfectly normal life. These include an additional little finger or webbing between two toes.

Other types, including serious heart defects and facial deformities such as cleft lip and palate, are more complex to manage. These may involve treatment spanning childhood and into adolescence.

Some birth defects are so severe the baby cannot live outside the womb. These kinds usually involve major malformation of essential structures, such as anencephaly where the brain fails to form.

When a single cause affects multiple systems in the body the birth defect is described as a syndrome. An example is Down syndrome. This is one of the most common birth defects in Australia and causes intellectual disability and other physical and learning challenges.

The outlook for children with syndromes, like the syndromes themselves, is highly variable. A syndromic birth defect is not necessarily more severe than an isolated birth defect. However, the involvement of multiple systems or structures may require ongoing management to ensure the best outcomes for the child and their family.

What causes birth defects?

Birth defects have two major causes, environmental and genetic.

Environmental causes (known as teratogens) include medicines that can harm the unborn baby. The most high-profile of these was thalidomide, which women took for morning sickness in the late 1950s and early 1960s. It led to thousands of babies born with irreversible congenital defects ranging from limb deformities (phocomelia) to facial malformations.

A more recently identified environmental cause of birth defects is the Zika virus, which leads to microcephaly (babies born with smaller-than-normal heads).

More everyday factors include alcohol and smoking, which have been associated with an increased risk of abnormalities. Estimates from the USA suggest 0.1-1% of children may be affected by alcohol in the womb. And smoking during pregnancy is associated with a range of conditions, including heart defects and facial clefts.

Environmental factors can also involve physical restriction that may occur in the womb from twin pregnancies.

The genetic causes of birth defects are equally diverse. These include chromosomal abnormalities in conditions like Down syndrome (an extra copy of chromosome 21) and errors in specific genes such as the FGFR3 gene, which causes a form of dwarfism.

But most causes remain a mystery

Recent US research examined the frequency and causes of birth defects by looking at medical records for over 270,000 births between 2005 and 2009. The researchers found 5,504 cases of birth defects, or about 2% of total births.

But they found the cause behind only one in five of these birth defects. The rest (79.8%) remained a mystery.

Of the known causes, 94.4% were genetic, 4.1% resulted from environmental exposure (teratogens) and 1.4% were linked with twin pregnancies.

The study also confirmed Australian findings that individual birth defects seem to affect a higher proportion of males than females; we still don’t know why.

Where to from here?

This study highlights reasons for hope. The 4.1% of birth defects resulting from teratogen exposure were mainly caused by uncontrolled diabetes in women before becoming pregnant. While the mechanism for this is unclear, this figure could be reduced through increased education of women intending to become pregnant to ensure their diabetes is controlled before and during pregnancy.

Yet, the finding that the cause of nearly 80% of birth defects remains unknown is confronting and highlights the scale of the task ahead.

In Australia, for instance, we do not have a clear picture of the types and frequencies of birth defects across the nation. This is because we have state-based systems that collect different information.

Birth defects are also diverse, affecting many different structures in the body. Each specific birth defect results from a different cause, most of which are genetic. Identifying the factors responsible requires each birth defect to be examined independently so that individuals with a particular condition can be grouped and studied together. This takes time, research and funding.

Greater support for genetics research and information collection on birth defects would allow us to understand the origins of these conditions. Only then can we be begin the task of intervention and prevention to reduce the burden of these conditions on health-care systems and families.

If you have concerns about birth defects, please speak to your doctor. For more information and support, contact the Genetic Support Network of Victoria or the Genetic and Rare Disease Network.

Peter Farlie receives funding from the National Health and Medical Research Council Australia.