A test for premature birth?

“A simple saliva test could help to cut the toll of potentially dangerous premature births,” the Daily Mail has reported. It says that new research has created a test that detects levels of the hormone progesterone, which can be used to identify those pregnant women most likely to give birth prematurely. According to the newspaper, high levels of progesterone help to stop the womb contracting before the full term of 40 weeks, whereas low levels put women at risk of delivering more than six weeks early.

In the study, the researchers analysed saliva samples from 92 pregnant women who were considered to be at risk of an early birth because of a previous premature delivery. The researchers then compared the levels of the hormone seen each week from 24 to 34 weeks of pregnancy with levels found in women who had babies born after 37 weeks.Twelve women who gave birth before 34 weeks were found to have lower levels of progesterone than those who had their babies at 37 weeks or later.

The small study had a few limitations but demonstrated the concept that a simple hormone test can have some predictive value. The research will also add to an understanding of the problem of early birth, hopefully leading to improved care for the 7% of babies born prematurely each year.

Where did the story come from?

This study was carried out by Dr Lachelin and colleagues from University College London and Kings College London. The study was funded by Tommy’s the Baby Charity and supported by an award from the National Institute for Health Research. It was published in the peer-reviewed, British Journal of Obstetrics and Gynaecology .

What kind of scientific study was this?

This was a cohort study in which the researchers measured the levels of the hormones oestriol (E3) and progesterone in the saliva of pregnant women known to be at risk of premature delivery.

The researchers explain that the rates of premature birth in developed countries have remained unchanged over several decades, affecting about 7% of deliveries. They also knew from previous work and animal studies that labour is preceded by biological changes, namely a decrease in progesterone and an increase in concentrations of the oestrogen-like hormone oestradiol (E2).

While studies have found no increase in the ratio of E2 to progesterone before the onset of term labour, there is an increase in the ratio of E3 to progesterone in the saliva prior to full-term labour and in women who deliver preterm.

In this study, the researchers took weekly saliva samples from women at increased risk of
preterm delivery from 24-weeks gestation onwards. The women were mainly recruited from 12 centres, (with a few self-referrals), as part of another study, the PREMET study. In the PREMET study, the researchers assessed the potential benefit of a drug in preventing premature birth in 892 women. Only the 111 women who provided saliva samples in this study were eligible for this subsequent research, and only 92 of these women consented or had sufficient samples taken for a complete analysis to be performed.

The researchers measured progesterone concentration, E3 concentration and E3 to progesterone ratio. They then made statistical adjustments to account for expected weekly changes in hormone levels and to allow for repeated measurements.

In the main analysis, they compared 64 women who delivered at term with the 12 women who delivered before 34 weeks and the 52 who delivered between 34 and 37 weeks.

The researchers also say that because of promising data from clinical trials, progestogen supplementation is now being widely investigated as a preventative intervention in women at risk of preterm labour.

What were the results of the study?

Salivary progesterone was significantly lower in the 12 women who delivered before 34 weeks than in those who delivered both at between 34 and 37 weeks or at term. The E3:progesterone ratio was also higher in the women who delivered before 34 weeks: this was in line with the progesterone results, but was not a statistically significant result.

What interpretations did the researchers draw from these results?

The researchers say that the measurement of saliva progesterone “may be of value in the prediction of early preterm labour” and in “determining which women might benefit from progesterone supplementation”.

What does the NHS Knowledge Service make of this study?

The lower progesterone concentration seen in the women who delivered before 34 weeks lends support to the theory that an imbalance between these hormones may be associated with preterm labour in some women.

As an exploratory study, this research does have some limitations in its methods, which should be considered when interpreting its results:

• This was a small, non-randomised study and therefore the 12 women who delivered before 34 weeks may have differed from those who delivered later in ways the researchers were unaware of. For example, most of those who delivered early already had lower levels of progesterone at 24 weeks. This could suggest that the women may have a predisposition to both lower progesterone and premature labour because of some other unknown factor.
• The selection methods used in the trial that originally supplied these women means they will not necessarily be representative of all women at risk of preterm labour. This means that further research will be needed to assess how applicable this test might be for general use among all pregnant women.
  ● A statistical test of how well the saliva samples discriminate between those women who will deliver early or not (its predictive power) was low. This suggests the test will need to be used alongside other clinical tools to improve its predictive power.
• As the study did not test progesterone supplementation, it is not possible to say from this research if this will be useful in preventing preterm births.

Overall, this study has shown that this simple test has some potential for use alongside other clinical tests and may, following further study, prove useful in identifying women at risk of preterm labour.