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Prediction &Prevention of spontaneous preterm birthLaleh Eslamian MD, Prof of Obstet& Gynecol, Perinatologist, TUMS
- 130 106 birth annually in the world.
- 4 106 die in the 1st 4 weeks of life.
- Main causes of neonatal death: PTB,
severe infection & asphyxia.
- PTB is responsible for about half of
neonatal deaths.
Iran, Health ministry data: 1,247,315 birth in 1392 in hospitals,1,481.734 total .
7.7% < 37w : 96000 7.7% < 2500g Iatrogenic PTB rate ? (20% in USA) 12% of births in Iran occurred <37 weeks in
2011 ( according to WHO data).
In theory, identification of risk factors for preterm delivery before conception or in early pregnancy provides an opportunity for intervention to prevent this complication.
However, many preterm births occur among women with no risk factors and there are few interventions that have been proven to prolong pregnancy in women at risk.
IDENTIFICATION OF RISK FACTORS FOR PRETERM BIRTH
The risk of PTB is highest when: 1)The previous PTB was in the pregnancy
prior to the current pregnancy (ie, no intervening term pregnancies) (15-30%)
2)There is a history of multiple PTBs (60%: 2)
Whether PTB of twins is associated with an increased risk of PTB in a subsequent singleton pregnancy is unclear.
Data are conflicting, but the bulk of evidence suggests that a prior preterm twin birth is associated with an increased risk of preterm birth in a subsequent singleton pregnancy.
Singleton after prior preterm twin gestation
The overall risk of spontaneous preterm birth in twin pregnancy is significantly higher in multiparous women whose previous singleton delivery occurred preterm:
67.3 versus 20.9% if the previous singleton delivery was at term (OR 7.8; 95% CI 5.5–11.2).
Twins after prior preterm singleton birth
Hx of abortion Short inter pregnancy interval Assisted reproduction Multiple gestation (reduction) Vaginal bleeding Infection (asymptomatic bacteriuria, periodontal disease, bacterial
vaginosis…) Genetic factors (maternal not paternal) Maternal age and race Life style (physical activity and work, stress, weight and weight changes,
smoking, substance abuse) Cervical & uterine factors (CL: 16-28w) Chronic maternal medical disorders, autoimmune disease, anemia, chronic
infection. Fetal: FGR, anomalies, male gender Hx of SIDS Biomarkers ( fibronectin & 30 others)
Risk factors for PTB
What should be done for prevention of PTB in primiparas?
Cervical shortening (effacement) is one of the first steps in the parturition process, preceding labor by several weeks.
As CL decreases in the 2nd trimester, the risk of spontaneous PTB increases, especially when effacement occurs early in the 2nd trimester.
Because effacement begins at the internal cervical os and progresses caudally, it is often detected on ultrasound exam before it can be appreciated on physical exam.
The cause of preterm cervical shortening is often unclear.
Cervical length (CL)
Routine US screening for short cervix in singleton pregnancies is suggested.
The protocol for initiating CL measurement is based on prior OB Hx.
CL measurement is not a sensitive screening test for prediction of PTB in multiple gestations with short cervix.
Cervical length
Normally, cervical length: stable between 14-28w
15 mm – 2nd centile 20 mm – 5th centile 25 mm – 10th centile 35 mm – 50th centile ***** 45 mm – 90th centile
NORMAL CERVICAL LENGTH
1) After 28 – 32w, a gradual decline in cervical length is normal.
2) The median cervical length is: 40 mm< 22w 35 mm @ 22 -32 w 30 mm> 32 w3) Cervical length is not significantly affected
by parity, race/ethnicity, or maternal height.
NORMAL CERVICAL LENGTH
TVS:
The most reproducible technique for CL assessment.
No management should be done on TAS results.
Procedure of CL measurement:- GA (14 – 24w)
- Empty the bladder ,dorsal lithotomy position
- Apply gel on probe and on the covering condom.
- Place the transducer in anterior fornix.
- Avoid pressure on the anterior lip.
- Enlarge the image to fill at least one half of the screen
- Locate int.os below the lower edge of mat. empty bladder.
- Place calipers between int. and ext. os
- Anterior & posterior lips of cervix should be equal.
- Measure 3 times: record the “shortest best”.
- Minimum of 3 minutes is needed to see funneling after pushing.
- Record absence or presence of funneling & CL.
Dx of short cervix when cervical length on TVS @16 -28 w:
≤20 mm in women with no prior preterm delivery
<25 mm in women with a prior preterm
delivery
DEFINITION OF SHORT CERVIX
The following strategies have no benefit in reducing recurrences:
Bed rest (adverse effects: DVT, muscle atrophy & stress)
mimetics (prophylactically)
Life style interventions :↓ manual labor
↑ Prenatal visits
Psychosocial supports
Diet supple: Fe, FA, Ca, Zn, Mg, fish oil
Prevention of PTB in women with previous PTB
These 2 strategies have proved to have benefit in
reducing recurrence:
1) Cervical cerclage
2) Progesterone
Prevention of PTB in women with previous PTB:
In cases with previous PTB:↓ 25% in PTB<34w ( 2 protocols)
1-Cerclage soon after 11 – 13w (normal scan)
2- CL measurement q2w (14 – 24w) → cerclage when CL < 25mm
Similar results for PTB but cerclage rate is reduced 50% in the
2nd.
Cervical cerclage:
Progesterone supplementation reduces the risk of preterm birth by about one-third:
1) in women with a singleton pregnancy who have had a previous spontaneous singleton preterm birth and
2) in women with a short cervix on ultrasound examination in the current pregnancy.
Meta-analyses of randomized trials have concluded that progesterone supplementation is protective against recurrent preterm birth and improves neonatal outcome. (2013 meta-analysis including 36 trials, comparing the benefits of progesterone supplementation with placebo)
Birth <34 weeks (relative risk [RR] 0.31, 95% CI 0.14-0.69) Birth <37 weeks (RR 0.55, 95% CI 0.42-0.74) Neonatal death (RR 0.45, 95% CI 0.27-0.76) Use of assisted ventilation (RR 0.40, 95% CI 0.18-0.90) Necrotizing enterocolitis (RR 0.30, 95% CI 0.10-0.89) Reductions in intraventricular hemorrhage, neonatal sepsis, and
retinopathy of prematurity were not statistically significant.
Spontaneous singleton preterm birth in prior pregnancy
Tx interventions is based upon both cervical length and prior pregnancy history.
The change in cervical length on subsequent US exams also appears to impact the risk of PTB in women diagnosed with a short cervix (<25 mm).
For women with a singleton pregnancy who have had
a previous spontaneous singleton preterm birth:
Progesterone Tx is suggested.
im injections of hydroxyprogesterone caproate
rather than vaginal progesterone.
Beginning @16 -20 and continuing to 36th w.
17-OHC 250 mg weekly.
Women with a singleton pregnancy who have had a prior spontaneous twin birth:
Progesterone Tx is suggested.
im injections of hydroxyprogesterone
caproate rather than vaginal progesterone.
Beginning @16 -20 and continuing to 36th
w.
17-OHC 250 mg weekly.
Women with midtrimester cervical shortening (≤20 mm <24 w) and no prior spontaneous singleton preterm birth:
vaginal progesterone Tx through the 36th w. Reasonable options include a vaginal
suppository (100 or 200 mg), gel (90 mg), or tablet (100 mg micronized progesterone).
Routine progesterone supplementation does not appear to be useful for preventing preterm birth in unselected multiple gestations.
For women with twin pregnancies and a previous spontaneous preterm birth: hydroxyprogesterone caproate.
For women with twin pregnancies and a short
cervix in the current pregnancy: vaginal progesterone.
Routine progesterone supplementation does not appear to be useful for preventing preterm birth in the setting of:
1) PPROM 2) After an episode of arrested preterm labor. There is no information on efficacy in
women with a positive fetal fibronectin test. The effect in women with a cerclage is
unclear.
A synthetic progestogen with minimal to no androgenic activity.
It is typically administered im. Doses have ranged from 25 mg every 5 days to
1000 mg/ w, beginning as early as 16w. We use 250 mg dose/w. Standard contraindications to progesterone
administration include hormone-sensitive cancer, liver disease, or uncontrolled hypertension.
FDA approved. Hypospadias in male offsprings. (when<11w) GDM: 3 fold in one study.
Hydroxyprogesterone caproate
Natural progesterone is typically administered vaginally. The advantage of vaginal progesterone is its high
uterine bioavailability since uterine exposure occurs before the first pass through the liver.
It also has few systemic side effects, but vaginal irritation can be bothersome and the drug needs to be administered daily.
Doses of 90 to 400 mg have been effective, beginning as early as 18 w.
Other options include a 100 mg micronized progesterone vaginal tablet or an 8 vaginal gel containing 90 mg micronized progesterone per dose.
Not FDA approved.
Vaginal progesterone preparations
An oral micronized preparation of natural progesterone also exists.
Daily doses of 900 to 1600 mg have been given.
Reported side effects include sleepiness, fatigue and headache.
Oral progesterone
Use of a pessary to prolong pregnancy in women with a short cervical length may be an effective, inexpensive, and easy to implement intervention.
In 2012, a multicenter trial randomly assigned 385 pregnant women with cervical length ≤25 mm at 20 to 23 w to use of a cervical pessary or expectant management . The majority of these patients (89%) had no history of previous PTB, and none were treated with progesterone or cerclage. The pessary group had a lower rate of spontaneous PTB than the expectant management group:
Delivery <28 w 2% vs 8% ,OR: 0.23, (95% CI 0.06-0.74)
Delivery <34 w 6% vs 27%; OR: 0.18, (95% CI 0.08-0.37)
A subsequent RCT published in 2013 found that use of a pessary did not reduce the rate of preterm delivery <34 w compared with no Tx.
Pessary
