Offering a standard biomarker test earlier in pregnancy could
potentially help doctors to better identify women at risk of giving
birth prematurely, thus enabling health services to focus
treatments on women at highest risk, according to a new study led
by King's College London.
A number of factors are used to determine if a woman is at risk
of giving birth prematurely, including a history of preterm births
or late miscarriages. Two further factors which clinicians normally
consider are the length of cervix and levels of a biomarker found
in vaginal fluid known as fetal fibronectin. The fibronectin
threshold traditionally used to categorise women's risk is 50
ng/ml, above which women are considered 'positive' and to be at
higher risk of giving birth prematurely. The researchers at King's
have further developed this into a quantitative test that provides
levels across the range (1 to 500 ng/ml).
In the study, researchers compared measurements of this new
fetal fibronectin test in the vaginal fluid of women at 18 to 21
weeks of gestation with measurements made at 22-27 weeks of
gestation, to see which time period offered the best prediction of
spontaneous preterm birth. Researchers also explored whether using
a low (10 ng/ml) and high (200 ng/ml) threshold would more
accurately classify a women's risk of giving birth prematurely.
Of the 898 high risk women followed in the study, only 3.8 per
cent of women with concentrations less than 10 ng/mL (tested at
18-21 weeks) delivered before 34 weeks of gestation, a similar rate
to that expected in a normal pregnancy. This compared to 2.9 per
cent in those tested later (22-27 weeks). In those woman over 200
ng/ml, similar proportions delivered after 34 weeks whether tested
early or late (39 versus 43 per cent).
The authors conclude that measuring fetal fibronectin at 18-21
weeks pregnancy appears to offer a similar predictive value to
measurements at 22-27 weeks. For both the early and standard tests,
there was a noticeable increase in relative risk between the lowest
and highest thresholds used in the study. Combining cervical length
with the biomarker test was found to improve the diagnostic
accuracy further.
However, the authors caution that these findings should not be
used as the basis of deciding whether to use an early test as well
as, or instead of, a later test. Further studies are required to
establish and validate the feasibility of using one and/or both
tests to determine risk in pregnant women.
Limitations of the study included the fact that interventions
were routinely offered to women with a history of pregnancy loss or
early preterm birth if a short cervix was detected, which may have
influenced the pregnancy outcome and slightly reduced the
predictive ability in this study, but ethically the study could not
be conducted without providing some intervention.
Professor Andrew Shennan, Professor of Obstetrics at King's
College London and consultant obstetrician at Guy's and St Thomas'
NHS Foundation Trust, said: "The aim of our study was to find
better ways of establishing the risk of women giving birth
prematurely in early pregnancy, to enable us to focus on the women
most likely to benefit from earlier intervention and close
monitoring during pregnancy. Instead of relying on the traditional
single threshold later in pregnancy we now can more accurately
identify those likely to be normal and those most in need of early
interventions, from the first half of pregnancy.
"We hope to carry out further trials to establish whether
biomarker testing at an earlier stage of pregnancy could help us to
intervene where necessary before cervical shortening is normally
detected, and thus improve the prospects of giving birth safely for
more women."
The paper, Quantitative Fetal Fibronectin at 18 Weeks of Gestation to Predict
Preterm Birth in Asymptomatic High-Risk Women, is published inObstetrics and Gynecology.