Clinical Pearls:
·
Women receiving transvaginal cerclage plus
17α-hydroxyprogesterone caproate had a 69% relative reduction in delivery at
less than 24 weeks of gestation when compared with women receiving cerclage alone.
·
These women also delivered babies that were heavier (2,547±1,009
g) as compared to women with only cerclage (2,326±1,250 g). (P=.03)
·
They also had fewer neonates with with 5-minute Apgar score
less than 7,10% in the cerclage plus 17α-hydroxyprogesterone caproate cohort
compared with 20% in the control cohort (P=.04).
·
There was no significant difference in delivery at less than
28 and less than 37 weeks of gestation, neonatal complications and admission to
NICU between the two cohorts.
·
The pilot study results indicate that the two therapies,
17α-hydroxyprogesterone caproate and cerclage, appear to be cumulative in their
benefit.
Preterm
birth is a major cause of neonatal morbidity and mortality with most
preterm-related deaths occurring among babies who were born very preterm
(before 32 weeks). Preterm birth is also a leading cause of long-term
neurological disabilities in children.[1]
As per WHO
statistics every year nearly 15 million babies are born preterm (1 in 10 babies) and it was
responsible for nearly 1 million deaths in 2013.
In
India, 3,341,000 babies are born preterm each year and 361,600 children under
five die due to direct preterm complications.[2]
More than 90% of babies born before 28 weeks of gestation in developing
countries succumb within first few days of birth while in developed countries
less than 10% babies of the same gestation die.[3]
Beside other
risk factors, a history of prior preterm birth is the single most important
risk factor for subsequent preterm birth.
A meta-analysis
by Berghella V et al published in obstetrics and gynecology journal compared
the outcome in singleton gestations with prior preterm birth that were managed
either by cervical length screening with cerclage for short cervical length or
history-indicated cerclage. The study concluded that cerclage is not indicated
in every woman with previous history of preterm birth but reserved for the
minority of women who develop a short cervical length.[4]
ACOG February 2014 Practice Bulletin reviews the guidelines for cervical cerclage in
women with a history of preterm birth based on history, physical examination,
and ultrasonographic findings.[5]
The
second modality of treatment for women with a prior preterm birth is 17α-hydroxyprogesterone
caproate. A study by Meis PJ et al
showed that weekly injection of 250 mg 17
alpha-hydroxyprogesterone caproate reduced the risk of preterm birth before 37
weeks by nearly 34%.[6]
The additive
effects of cerclage plus 17 alpha-hydroxyprogesterone caproate versus only
cerclage in patients with a prior spontaneous preterm delivery has not been
studied.
The
recent study published in obstetrics and gynecology November 2016 issue compared
the prolongation of pregnancy and perinatal outcome in among women with a prior preterm birth
who received cerclage compared with cerclage plus 17α-hydroxyprogesterone
caproate.
This
retrospective cohort study recruited patients with vaginal cerclage and prior
history of preterm birth between 16-36 weeks of gestation were identified over
a course of 10-year period from July 2002 to May 2012.
A total
of 411 women with cerclage were identified out of whom 260 met the inclusion
criteria. Of these, the control arm of 171
women continued the pregnancy with cerclage alone while 89 women in the study arm
received 250 mg of 17α-hydroxyprogesterone caproate injections weekly along
with the cerclage. In 46 women with a history based cerclage the injections
were started prior to surgery and in 43 patients they were started after the
procedure.
The primary
outcome was delivery before 24 weeks while the secondary outcomes were delivery
at less than 28 and less than 37 weeks of gestation as well as preterm prelabor
rupture of membranes (PROM), delivery mode, neonatal intensive care unit
admission, 5-minute Apgar score less than 7, necrotizing enterocolitis, grade 3
or 4 intraventricular hemorrhage, and birth weight.
The two
groups were identical in terms of maternal demographics and gestational age of receiving
cerclage.
It was
seen that women receiving transvaginal cerclage plus 17α-hydroxyprogesterone
caproate had a 69% relative reduction in delivery at less than 24 weeks of
gestation when compared with women receiving cerclage alone.
These
women also delivered babies that were heavier (2,547±1,009 g) as compared to
women with only cerclage (2,326±1,250 g). (P=.03)
They
also had fewer neonates with with 5-minute Apgar score less than 7. 10% in the
cerclage plus 17α-hydroxyprogesterone caproate cohort compared with 20% in the
control cohort (P=.04).
There
was no significant difference in delivery at less than 28 and less than 37
weeks of gestation between the two cohorts.
Both
the cohorts also have similar mode of delivery, neonatal intensive care unit
admission, intraventricular hemorrhage (grade 3 or 4), or necrotizing
enterocolitis.
A
secondary analysis studies the relationship between examination and ultrasound
indicated cerclage with the additive effect of 17α-hydroxyprogesterone caproate
as compared to history indicated cerclage. There was a 91%
and 89% reduction in delivery at less than 24 and less than 28 weeks of
gestation, respectively when progesterone was continued.
The
study has multiple strengths and limitations. The investigators understand that
the study had a small sample size and limitations of adjusting for several
variables. They also caution the readers to interpret the results of the study carefully
as more large, adequately powered multicenter prospective trial studies are needed
before a recommendation can be made.
The pilot
study results indicate that the two therapies, 17α-hydroxyprogesterone caproate
and cerclage, appear to be cumulative in their benefit.
[1]http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm
[2] http://www.everypreemie.org/wp-content/uploads/2016/02/India-revJan2016.pdf
[3] http://www.who.int/mediacentre/factsheets/fs363/en/
[4] http://journals.lww.com/greenjournal/Abstract/2011/07000/Cervical_Length_Screening_With.20.aspx
[5] Cerclage
for the management of cervical insufficiency. Practice Bulletin No. 142.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2014;123:372–9.
[6] https://www.ncbi.nlm.nih.gov/pubmed/12802023
