Multiple
births are steadily climbing all around the world. Developed countries making a
significantly higher contribution to this rising rate because of women delaying
childbirth, elderly mothers and increased use of ARTs.
US twinning
rate rose by 101% from 1980 – 2006. About 68,339 twins were born in 1980 that
doubled to 137,085 in 2006. The US current twin birth rate is 33.9 per 1,000
live births.
According to WHO the rate of singleton preterm
birth ranges between 5% to 18% for singleton pregnancy worldwide, the average
being 11%, while almost 60% of twins are delivered preterm. About 13% of twins are
born before 34 weeks and 7% before 32 weeks.
A multitude
of prophylactic therapies have been in use like to gain valuable gestational
weeks by supplementing progesterone, vaginal pessaries and strict bed rest without
substantially significant results.
The next
step was to develop essential biomarkers that can predict the chances of
preterm births. Cervical length(CL) has long been
used as a predictive indicator of preterm birth. An earlier review has shown
that a CL < or=20 mm at 20-24 weeks' gestation was the most accurate in predicting preterm
birth at <32 and <34 weeks respectively. Many other studies have combined
fetal fibronectin with CL.
Studies in singleton pregnancies have also shown
that the relationship between CL and spontaneous preterm birth (sPTB) is dependent
on the Gestational age (GA) at which the USG is done, a shorter CL early in pregnancy
has greater significance than the same measurement at a later GA.
Such studies
in twins are few with small sample size and are not comparable. Previous
meta-analysis has shown a relationship between CL and sPTB in twins, but did not
correlate the GA at screening with prediction of sPTB.
This recent
study published in the May, 2016 issue of BJOG is a meta-analysis of independent
patient data(IPD), and provides a new estimate in which CL and GA are treated
as continuous variables to predict weeks at delivery.
Specific
data collected for each patient from the original authors of the study included
the exact GA at CL screening, the CL measurement in millimeters and the exact
GA at birth in weeks and days.
23 studies
met the inclusion criteria, resulting in a total of 6188 transvaginal scans,
performed on 4409 twin pregnancies.
In the first
analysis, univariate regression was performed to see what other confounders like
maternal age, ethnicity, smoking, BMI,
chorionicity, parity and study location affects the GA at birth.
As second analysis
multinomial logistic regression model was derived predicting the probabilities
of very early preterm, early preterm, late preterm, and term birth using
GA at USG and CL as continuous variables.
Important
study results were:
- BMI was the only other variable that correlated significantly with GA at birth in the univariate analysis, but when it was incorporated into multinomial logistic regression model with CL and GA at ultrasound, prediction of GA at birth did not improve.
- A short CL measured at ≤20+0 weeks by USG indicates a probability of birth significantly earlier than if the same CL was taken at a later GA.
- When screening before 18+0 weeks, any cervical length <30 mm has a higher risk of sPTB at ≤28+0 weeks in twins than in singletons.Whereas the best prediction of birth between 28+1 and 36+0 weeks was provided by screening at ≥24+0 weeks.
- A 100% probability of preterm birth not occurring before 28 weeks is achieved by CL of 65 mm and 43 mm at ultrasound GA at ≤18+0 weeks and at 22+1 to 24+0 weeks, respectively.
In
the third analysis, the accuracy of the model to correctly predict term
delivery as compared to preterm was assessed. The model has a 68.2% true negative
rate, classifying correctly those who were predicted to deliver at ≥36+1 weeks, compared
with 26.2, 13.3 and 36.2% correctly predicted to deliver at ≤28+0,
28+1 to 32+0 and 32+1 to 36+0 weeks,
respectively (true positive rate).
Although
effective intervention for sPTB in twins are limited, the study provides risks
of very early, early and late preterm birth, so a personalized cost
effective delivery plan, optimal timing of corticosteroids and referring to
neonatal unit can be managed. It also justifies serial CL measurements, so that
early and late sPTB could be predicted.
To
conclude the authors, recommend to start the screening at ≤18+0 weeks
with repeat screening at >22+0 weeks; this best identifies
the patients that may deliver very early at ≤28+0 weeks as well
as the more common later group of sPTB between 28+0 to 36+0 weeks.
References:
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