Key protein in childbirth contractions identified
"Australian scientists discover protein that triggers child birth," the Mail Online reports. The protein (β-inhibitory protein) is thought to cause the uterus to contract and could possibly be used to induce labour in obese women.
The website reports on a study looking at what causes the muscles of the uterus (womb) to contract during labour. Researchers found decreased activity of the gene that produces β-inhibitory protein in the uterine muscle leads to stronger contractions.
However, the study did not prove these mechanisms trigger the complex process of childbirth. Nor did it uncover any mechanisms that have any bearing on preventing premature births.
In this snapshot of women undergoing caesarean section, the study found lean women had increased levels of β-inhibitory protein activity. However, overweight women with a body mass index (BMI) over 30 had lower levels (associated with weaker contractions).
The researchers suggest they might be able to suppress this gene in the future. This could increase the strength of contractions in obese women, who may be more at risk of failure to progress during labour. However, this potential treatment was not assessed in the study.
Where did the story come from?
The study was carried out by Australian researchers from Monash University, the University of Melbourne, the Royal Women's Hospital, Victoria, and the University of Newcastle, New South Wales.
It was funded by the National Health and Medical Research Council of Australia and was published in the peer-reviewed medical journal, Nature Communications.
The Mail Online's reporting on the study was both inaccurate and confusing. Claims that the trigger for labour has been definitely identified are incorrect. This was a small study that can only suggest an association and not prove cause and effect.
Also, somewhat oddly, the Mail claims that the research could be used to prevent premature births. While it could conceivably lead to a medication that could be used to induce labour in women who are overdue, it is difficult to see how it could lead to a treatment to prevent premature births.
What kind of research was this?
This was a cross-sectional study comparing the activity of muscle cells in the uterus in women at term but not in labour, compared with women at term in labour.
It aimed to see if the ability of the muscle cells to take longer to contract (leading to stronger contractions) differed between the two groups. They then analysed whether any differences were associated with increased body mass index (BMI).
As this was a cross-sectional study, it can only assess the activity and muscle contractibility at one point in time. It cannot prove that the gene expression was responsible for labour not progressing in these women. But this study can provide associations that may be used in further research.
Previous research has found that in obese women, the uterine muscle is less able to contract compared with women of a normal weight. This can lead to failure for the labour to progress and ultimately the requirement for caesarean section.
The researchers wanted to investigate whether this was a result of a problem in the ability of the uterus muscle to contract.
A gene called "human ether-à-go-go-related gene" (hERG) plays a role in the number of potassium channels in heart muscle. The channels are essentially the building blocks of muscle activity in the same way brain cells are essential for thinking.
The channels influence the length of time between muscle contractions. When the time period is short (a short time for the muscle to relax in between contractions), the contractions are weak.
During pregnancy, it is important that the muscle cells do not contract strongly so that the foetus can grow. However, strong contractions are required during labour.
This study wanted to see if these hERG protein channels for potassium are also present in the muscle cells in the uterus.
What did the research involve?
The researchers recruited women who required a caesarean section so that they could compare muscle contractibility before and during labour using tissue samples.
They looked at biopsies of the uterine muscle of women who had undergone planned caesarean sections but had not gone into spontaneous labour, comparing these samples with those from women who required an emergency caesarean section.
The researchers recruited a group of 43 women with singleton pregnancies undergoing planned caesarean section between 37 and 40 weeks who had no signs of labour.
These planned caesareans happened if:
- a woman had had a previous caesarean section
- a woman had had a third or fourth-degree tear
- if the baby was in breech presentation (head up)
The second group were 27 women undergoing emergency caesarean section after the spontaneous beginning of labour at term.
These emergency caesareans happened if:
- there were signs of foetal distress or foetal "compromise"
- there was failure to progress in labour
Women were excluded from the study if they had an infection, high blood pressure or diabetes.
After delivery, all women were given an injection of oxytocin into the bloodstream. Oxytocin is a hormone that controls bleeding following delivery and stimulates the flow of milk.
Biopsies of the uterine muscle were taken three to five minutes after the oxytocin was administered. The samples were used for protein analysis and electrophysiology and conduction studies. The results from each group were then compared.
What were the basic results?
The researchers found that hERG potassium channels are present in the muscle of the uterus. When they are blocked with a drug (dofetilide), the muscle takes longer to relax between contractions so the contractions are stronger.
In women who had gone into spontaneous labour before they had a caesarean section, the level of activity of the potassium channels was reduced compared with women who had not yet started labour. This means that stronger contractions were possible – a necessity for successful labour.
This reduced activity was associated with a higher number of the β-subunit of the hERG potassium channel. This subunit inhibits the potassium channel, compared with the α-subunit, which encourages it.
The level of activity of the potassium channel had not reduced in 14 out of 16 women with a BMI over 30 whose labour had started but failed to progress. These women required a caesarean section.
These women also had higher activity levels in the potassium channels because they had proportionately lower levels of the inhibitory β-subunit.
The researchers say that the β-subunit is increased by oestrogen and that oestrogen levels can be dysfunctional in the pregnancies of women with a high BMI. They also report a link between higher cholesterol levels and hERG function.
How did the researchers interpret the results?
The researchers concluded that, "hERG proteins, both α-pore-forming and β-inhibitory subunits, are present in human [uterine muscle] in late pregnancy.
"The levels of β-inhibitory subunit are elevated in labour tissues and are associated with a decrease in hERG activity and an increase in contraction duration.
"These changes that occurred in lean labouring women did not occur in obese labouring women, and could explain the increased incidence of failure to progress in labour, necessitating caesarean delivery in obese women."
Conclusion
This study has found that hERG potassium channels, which have a role in the speed and strength of heart muscle contractions, are also present in uterine muscle in late pregnancy.
The study suggests that the activity level of the potassium channels increases in normal labour because of a reduced number of the β-inhibitory subunit. This increase makes it possible for longer and stronger contractions.
This finding was the opposite for obese women who had started labour but failed to progress. These women had a higher proportion of the β-inhibitory subunit compared with the α-subunit. The researchers say this could be because of their increased levels of oestrogen and cholesterol.
A drug that inhibits the α-subunit could theoretically prolong the ability of the muscles to contract, but this was not looked at in this study.
The drug (dofetilide) used on the muscle cells in the laboratory in this study is licensed for people with atrial fibrillation. However, its effects and safety have not been studied in pregnant women.
There are several limitations of the findings of this study. It was based on a small number of women and presumed that the level of activity of the potassium channels in the uterine muscle was related to the stage of pregnancy.
Rather than being a single cause of labour failing to progress, a change in the ability of the muscle to contract is likely to be one of several factors that influence childbirth.
We need to see more research before any changes to the care of pregnant women or a new drug treatment would be advised.
If you are pregnant and overweight, trying to lose weight during your pregnancy is not recommended (unless specifically advised by a health professional).
The best way to protect your and your baby's health is to go to all your antenatal appointments so that the midwife, doctor and any other health professionals can keep an eye on you both.
They can manage the risks that you might face related to your weight, and act to prevent – or deal with – any problem.
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