Preterm labor

An update on tocolytics & corticosteroids

• Update in Dec 2014 deferred

2014 Update deferred

20 Nov 2015

Jan 2016

When to consider repeat course of corticosteroids

Update #1

“…should only be considered with caution in those pregnancies where the first course was given at <26+0 weeks of gestation and another obstetric indication arises later in pregnancy.”

“…may be considered if the previous treatment was given >2weeks prior, the gestational age is <32+6weeks, and the women are judged by the clinician to be likely to give birth within the next week.”

Which tocolytics?

Update #2

• Tocolytics reviewed:

MgSO4, NO2, B2-agonist, PSI, Nifedipine, Atosiban

• Choice of first line therapy:

either atosiban or nifedipine

Expert Opin Drug Saf 2016 May 9

• 510 women in TPL between25+0 and 34+0 wks

• Randomized to receive nifedipine / atosiban

• Corticosteroid (+ MgSO4 if <32wk)

www.thelancet .com Published online March 1, 2016

Primary outcome: a composite of adverse perinatal outcomes

Conclusion: nifedipine or atosiban results in similar perinatal outcomes.

www.thelancet .com Published online March 1, 2016

• Time to delivery longer with nifedipine than atosiban in women with intact membranes

– Median 24d vs 14d, p=0.0412

• Side effects leading to discontinuation

– Nifedipine 6% vs atosiban 3%, RR 2.2 (0.91-5.33)

www.thelancet .com Published online March 1, 2016

www.thelancet.com Published online March 1, 2006

Tocolysis for 48hrs

0

10

20

30

40

50

60

70

80

Cost (GBP)

Nifedipine Atosiban

• Nifedipine

• oxytocin receptor antagonist

– if nifedipine contraindicated

• Do not offer betamimetics for tocolysis

Maintenance tocolysis?

Update #3

Peri-viable birth

Update #4

• Assessment for resuscitation does not mean

– resuscitation always undertaken or deferred, or

– every possible intervention need be offered

• A stepwise approach concordant with neonatal condition and parental wishes is appropriate.

• Corticosteroid

– 23+0 to 23+6 weeks: Discuss with the women

– 24+0 to 25+6 weeks: Consider

– 26+0 to 33+6 weeks: Offer

– 34+0 to 35+6 weeks: Consider

Late preterm

Update #5

• 17 MFM units across USA 2010-2015

• Singleton (34+0 - 36+5 wk) at high risk for preterm delivery – Preterm labor (Cx ≥3cm dilated or 75% effaced)

– PPROM

– Planned preterm delivery between 24hr and 7d

• Ineligible if – Likely to deliver within 12hrs (e.g. active bleeding,

PPROM + UC≥6/hr, Cx dilatation ≥8cm, NRFS) – Previously received a course of betamethasone – Pregestational diabetes – Chorioamnionitis – Major fetal malformations

• Intervention: Betamethasone vs placebo

• Primary outcome – Need for respiratory support within 72hrs after birth

• CPAP or high-flow nasal cannula for ≥2hrs,

• Supplemental O2 with FiO2 ≥0.3 for ≥4hrs,

• ECMO, or

• Mechanical ventilation.

• Tocolysis not part of the protocol

• >80% in the trial delivered <37wk

– Time from randomization to delivery: similar

• 60% in betamethasone group received 2 doses

• Primary outcome: significant ↓ – 11.6% vs 14.4%, RR 0.80, 95% CI 0.66-0.97

• Neonatal hypoglycemia (glu <40mg/dl): significant ↑ – 24.0 vs 14.9%, RR 1.61, 95% CI 1.38-1.88

– Rate in betamethasone gp ≈ that expected in late preterm

• Maternal outcome: similar

• Routine glucose monitoring for late preterm newborns advocated by AAP

• Lack of long-term info

Recommendation • Singleton (34+0, 36+6 wk) at high risk for preterm birth in 7 days (<37wk):

Recommend betamethasone

• Symptomatic: 3cm dilatation or 75% effacement before betamethasone

• Standard guidelines for neonatal hypoglycemia in late preterm newborns

• Against use of tocolysis to complete the steroid

• NO for conditions not studied in the trial

• Singleton (34+0, 36+6 wk) at imminent risk of preterm birth

in 7 days: Betamethasone may be considered

• Not with chorioamnionitis

• No tocolysis or delay in indicated preterm delivery

• No if already exposed to antenatal corticosteroids

• Monitoring of neonatal blood glucose for late preterm infants recommended

• Corticosteroid

– 23+0 to 23+6 weeks: Discuss with the women

– 24+0 to 25+6 weeks: Consider

– 26+0 to 33+6 weeks: Offer

– 34+0 to 35+6 weeks: Consider

On the horizon

Update #6

“LIPINDORA”

Take-home

• A single repeat course of corticosteroid – If prior course ≥7 days previously and

– Risk of preterm birth <34wk remains

• Nifedipine 1st line; Atosiban as indicated; No B-agonist

• Maintenance tocolysis not recommended

• Corticosteroid & tocolysis considered at 23 wk

• Corticosteroid considered for late preterm

Thank You