Australia - Babies Born With A Curved Spine: Nature And Nurture At Work

Scientists have shed new light on the relationship between hypoxia during pregnancy and congenital birth defects.

An international team of scientists has made a landmark discovery that could help women minimize their risk of having a baby born with congenital birth defects.

The team, led by scientists from Sydney’s Victor Chang Cardiac Research Institute (VCCRI), show for the first time in the journal Cell how ‘nature’ and ‘nurture’ interact to increase the severity and likelihood of developing birth defects, including abnormalities in the heart, kidneys, brain, limbs, and cranio-facial regions (ie. cleft palate).

They demonstrated how hypoxia, or insufficient oxygen during pregnancy, when combined with a genetic risk factor of having only one functioning copy of the MESP2 and HES7 genes, dramatically increases the chances of a baby being born with congenital scoliosis, a malformation of the spine that affects around one in 1000.

Hypoxia during pregnancy can be caused by a variety of circumstances including poorly controlled sugar levels in diabetics, smoking, high altitude, prescription and recreational drug-use, anemia, or a poorly functioning placenta.

“We’ve long suspected that it is genes or our environment that cause birth defects, but up until now, the majority of these have been largely unknown,” said senior author Professor Sally Dunwoodie, Head of the Embryology Laboratory at the VCCRI.

Apart from studying individuals with congenital scoliosis, the team also tested the genetic risk factor in a mouse model combined with the presence of hypoxia. They found a marked increase in spinal abnormalities in the offspring, when the mothers were exposed to just eight hours of low oxygen during an entire 21-day pregnancy.

“We found that the combination of the genetic risk as well as exposure to low oxygen, resulted in our subjects being up to ten times more likely to develop congenital scoliosis, than those that only had the genetic risk factor,” said Dunwoodie.

“What this brief period of low oxygen essentially did was disrupt the pathway responsible for development of the spine, and we know that the same pathway is used in the development of limbs and many organs, including the heart, kidneys, brain and cranio-facial region,” she added.

According to Professor Bob Graham, Executive Director of the VCCRI, around a quarter of patients with congenital scoliosis also have some form of congenital heart defect, indicating that a single environmental insult, such as hypoxia, can potentially affect the development of more than one organ in the body.

“It may not necessarily be a lack of oxygen that allows the underlying gene defect to be revealed, it could be a lot of other environmental factors, such as anemia or lack of folate. But the message is, if you have family history of disease or you know you have a defective gene, mums need to be extra careful during pregnancy,” added Graham.

The team has begun working on similar studies in congenital heart defects, which affect around one in every 100 babies born in Australia every year.

The article can be found at: Sparrow DB et al. (2012) A Mechanism for Gene-Environment Interaction in the Etiology of Congenital Scoliosis.

Rebecca Lim | Health & Medicine

AsianScientist

Source: VCCRI