StudyMRCOG

DELIVERING MEDICAL EDUCATION BEYOND BOUNDARIES

MRCOG Part 2
Summary

Topic – Antenatal
corticosteroids to reduce
neonatal morbidity & mortality
Delivered By: Dr.Swati Varma
Course Director Mentor @ StudyMRCOG

MEMBER
The CPD Certification
+91 9094 200 800 +447464245285 +447341981539 Service [email protected]
Visit us at www.studymrcog.com StudyMEDIC - ACCREDITED GLOBAL PARTNER FOR EFOG-EBCOG COURSES Contact: +91 9094 200 800 StudyMEDIC - ACCREDITED GLOBAL PARTNER FOR EFOG-EBCOG COURSES
Email: [email protected]
 • Maternal administration of antenatal corticosteroids before
anticipated preterm birth is one of the most important
interventions to improve neonatal outcomes
• They are effective in reducing neonatal respiratory morbidity and
other complications of prematurity.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Benefits of corticosteroids in preterm labour & birth

• A course of antenatal corticosteroids given within 7 days prior to

preterm birth reduces perinatal and neonatal death and respiratory
distress syndrome
• A Cochrane systematic review investigating the effects of
corticosteroids administered prior to anticipated preterm birth found
high certainty of the benefit of antenatal corticosteroids for the
neonate
• There was moderate certainty evidence that antenatal
corticosteroids reduce intraventricular haemorrhage and reduce
developmental delay in childhood.
• No studies were identified that showed direct beneficial effects of
antenatal corticosteroids for the women.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Benefits in planned caesarean birth at term

• Compared with vaginal birth, infants born by caesarean birth are

at greater risk of respiratory distress syndrome, transient
tachypnoea of the newborn and admission to the neonatal
intensive care unit (NICU).

Recommendation
• NICE Clinical Guideline CG132 Caesarean Section recommends
that planned caesarean birth should not routinely be carried out
before 39 weeks gestation

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Evidence for Recommendation
• Risk of respiratory morbidity at term is low (5%) and decreases
with advancing gestational age. Ideally, planned caesarean
births should be undertaken at or after 39 weeks gestation
When a planned caesarean birth is being undertaken before 39
weeks gestation, corticosteroids may be considered to reduce
the risk of neonatal respiratory morbidity.
• Recommendation
• For women undergoing planned caesarean birth between 37
and 38 weeks an informed discussion should take place with the
woman (and her family members or carers as
appropriate) about the potential risks and benefits of a course of
antenatal corticosteroids.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Although antenatal corticosteroids may reduce admission to the
neonatal unit for respiratory morbidity in planned caesarean birth
at 37 to 38 weeks gestation, it is uncertain if there is any reduction
in respiratory distress syndrome, transient tachypnoea of the
newborn or neonatal unit admission overall.

• Antenatal corticosteroids may result in harm to the

neonate which includes hypoglycaemia and potential
developmental delay.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Evidence for recommendation
• Recommendation supported by a Cochrane systematic
review that found that steroids may reduce admission to the
neonatal unit for respiratory morbidity, but the quality of the
evidence was low and came from a single trial.

• Further studies of higher quality and larger sample sizes are

required. There are several ongoing trials that may inform future
guidelines.
•

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Risks and benefits of antenatal corticosteroids to inform discussions with
the woman

• Risks and Benefits at 22 to 34 weeks gestation

Benefits Reductions in these conditions are most likely to

be seen if birth is 24 to 48 hours after starting
Highly likely to reduce: treatment.

• perinatal mortality
A reduction in respiratory morbidity
(but not mortality or intraventricular
• neonatal death
haemorrhage) likely to be seen if birth within 7
days of starting treatment.
• respiratory distress syndrome
Likely to reduce:
• intraventricular haemorrhage
• developmental delay in childhood
+91 9094 200 800 +447464245285 +447341981539 [email protected]
Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Harms

Likely to affect:
• maternal glucose tolerance for up to 5 days after administration (with higher
risk in diabetic women)

Likely to reduce:

• birthweight if birth more than 7 days after steroids

•
No benefits are likely to be seen if birth is more than 7 days after starting
treatmen

May increase psychiatric and behavioural diagnoses if children born at term

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Uncertainties
• There is less evidence for women with multiple pregnancy

Effects of unnecessary antenatal corticosteroids (ie. if birth more

than 7 days after steroids) are not well described.
• While no long term harms have been proved, large scale
observational studies for necessary pharmacovigilance are
lacking

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Risks and Benefits at 35 to 36 weeks gestation

• Benefits

Likely to reduce:
• respiratory support
• Harms

Likely to increase:
• neonatal hypogylcaemia
• May increase:
• psychiatric and behavioural diagnoses if children born at term

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Uncertainties

While no long term harms have been proven, large scale

observational studies necessary for pharmacovigilance are
lacking.
• Benefits seem unlikely if birth is more than 7 days after starting
treatment, but this has not been studied in women at this
gestation.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Risks and Benefits before planned caesarean birth at term 37 to 39
weeks gestation

• Benefits

May decrease:
• admission to NNU with respiratory morbidity
• Harms

May reduce:
• educational attainment at school age

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Uncertainities
• There is uncertainty as to whether there is any reduction in respiratory
distress syndrome, transient tachypnoea of the newborn or neonatal unit
admission overall.
• Short term complications such as hypoglycaemia have not been
rigorously studied but are likely to also apply at these gestational ages.
• Benefits seem unlikely if birth is more than 7 days after starting treatment,
but this has not been studied in women at this gestation.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Risks and Benefits of rescue course if treatment more than 7 days ago

• Benefits of Rescue Course

• Likely to reduce:
• need for respiratory support

Harms
• Likely to reduce:
• birthweight (mean difference 80g), head circumference and
length and neonatal blood pressure
• Uncertainities

Dose effects are seen for harms

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 At what gestational age should antenatal corticosteroids be discussed
and offered?

• The gestational age range at which antenatal corticosteroids

provide benefit and should therefore be considered or offered,
remains controversial
• Recommendation

Cortocosteroid administration has benefits when administered to

women in whom imminent preterm birth is anticipated (due to
established preterm labour, preterm prelabour rupture of
membranes (PPROM) or planned preterm birth) before 24 weeks
gestation
The obstetric and neonatal team should discuss the
administration of corticosteroids at the early gestations with the
woman in the context of her individual circumstances and
preference

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Evidence for Recommendation

The benefits of corticosteroids at the threshold of viability are

supported by a systematic review and meta-analysis of obervational
studies, and recommended by guidance from the British Association of
Perinatal Medicine.
Recommendation
Corticosteroids should be offered to women between 24 and 34
weeks gestation in whom imminent preterm birth is anticipated either
due to established preterm labour, [PPROM] or planned preterm birth
• Evidence for Recommendation

Corticosteroids recommended by a Cochrane systematic review of

randomised controlled trials and supported by NICE Guideline NG25
Preterm Labour and Birth
+91 9094 200 800 +447464245285 +447341981539 [email protected]
Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Recommendations
Clinicians and women should consider the balance of risks and
benefits of corticosteroids in women in whom imminent preterm
birth is anticipated from 35 to 36 weeks gestation.
Evidence for Recommendation
In late preterm birth, steroids have short term respiratory benefits
for the neonate but increase the likelihood of neonatal
hypoglycaemia.
• This is addressed in the Cochrane systematic review and in
• NICE Guideline NG25 Preterm Labour and Birth.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Multiple pregnancy
• Recommendation
Women with twins and triplets should be offered targeted antenatal
corticosteroids for early birth in line with recommendations for singletons
• Evidence for Recommendation

The majority of antenatal corticosteroid trials have excluded women

with multiple pregnancy so there is little direct evidence of benefit in
twins or higher order multiple pregnancy.
• However, there is no indication that the effects of corticosteroids are
different in multiple pregnancies than singletons in a Cochrane
systematic review of randomised controlled trials.
Recommendation
Uncertainties around the benefits and risks of antenatal corticosteroids
in twins and triplets should be discussed with women
+91 9094 200 800 +447464245285 +447341981539 [email protected]
Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Recommendation
Single or multiple untargeted (routine) courses of corticosteroids
should not be used in twin or triplet pregnancy.
• Women should be informed that there is no evidence of benefit
in using untargeted administration of corticosteroids.
• Evidence for Recommendation
NICE Guideline NG137 Twin and Triplet Pregnancy recommends
against the use of single or repeat doses of untargeted steroids
due to limited, low quality evidence.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Women with diabetes mellitus
• Recommendation
Diabetes should not be considered an absolute contraindication to
antenatal corticosteroids for fetal lung maturation
In women with diabetes who are receiving corticosteroids, additional
insulin should be given according to an agreed protocol. Close
monitoring should be undertaken.
• For women with diabetes undergoing planned caesarean
birth between 37 and 38 weeks an informed discussion should take
place with the woman about the potential risk and benefits of a
course of corticosteroids. Corticosteroid administration is associated
with increased rates of neonatal hypoglycaemia
Evidence for Recommendation
NICE Guideline NG3 Diabetes in Pregnancy addresses the use of
antenatal corticosteroids in women with diabetes. Guidelines on the
topic have also been produced by the Joint British Diabetes Societies
for Inpatient Care
+91 9094 200 800 +447464245285 +447341981539 [email protected]
Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Pregnancies complicated by fetal growth restriction,
pre-eclampsia or antepartum haemorrhage

• Recommendation
Birth should not be delayed for antenatal corticosteroids if the
indication for birth is impacting the health of the woman or her
baby.
NICE Guideline NG25 Preterm Labour and Birth recommends a
course of antenatal corticosteroids should be offered if planned
early birth is necessary for hypertension in pregnancy.

If imminent preterm birth is likely, a course of antenatal

corticosteroids should be offered to women whose babies are
thought to be small-for-gestational-age (SGA) or to have fetal
growth restriction.Women should be counselled about the lack of
evidence to guide care

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Evidence for Recommendation
There is little direct evidence of benefit in SGA babies, but
equally there is little evidence that antenatal corticosteroids
perform differently in babies with growth restriction compared to
the overall preterm population.
RCOG Green-top Guideline No. 31 on SGA babies recommends
that women with an SGA baby should receive antenatal
corticosteroids to accelerate fetal lung maturity and reduce
neonatal death and morbidity.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Preterm, prelabour rupture of membranes
• PPROM complicates up to 3% of pregnancies and is associated with 30%
to 40% of preterm births
Recommendation
Antenatal corticosteroids should be offered to women with PPROM, who
are at increased risk of preterm birth
Evidence for Recommendation
A meta-analysis of 17 randomised controlled trials has demonstrated
that the administration of corticosteroids to women with PPROM reduces
the risks of respiratory distress syndrome and intraventricular
haemorrhage
Recommendation
There is currently limited evidence to recommend repeat courses of
antenatal corticosteroids if a woman remains at imminent risk of preterm
birth seven days after administration of antenatal
corticosteroids.However, a further course may reduce the need for
respiratory support.
+91 9094 200 800 +447464245285 +447341981539 [email protected]
Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Evidence for Recommendation
The administration of one or more repeat courses of
corticosteroids is addressed later in this summary

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 What is the optimum dose and route of administration for a course of
antenatal corticosteroids?

• Antenatal corticosteroids are designed to cross the placenta.

They are given at high doses that have been unchanged since
Liggins' and Howie's original experiments in the 1970s and have
not been optimised for human pregnancy.
• Two types of antenatal corticosteroids have been widely
tested and used in clinical practice -
betamethasone and dexamethasone. These are synthetic
fluorinated corticosteroids, with similar activities.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Dexamethasone phosphate regimens

Recommendation

In the UK it is recommended that24 milligrams

dexamethasone phosphate is given intramuscularly
in two divided doses of 12 milligrams, 24 hours apart.
Or 4 divided doses of 6 milligrams,
12 hours apart

Evidence for Recommendation

A Cochrane systematic review found that

dexamethasone, compared with
betamethasone, reduced the risk of intraventricular
haemorrhage.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Betamethasone sodium phosphate / acetate mix regimen

• Recommendation
An alternative is:
• 24 milligrams of betamethasone sodium phosphate/acetate mix
given intramuscularly in two divided doses of 12 milligrams, 24 hours apart.
• Evidence for Recommendation
Betamethasone acetate/phosphate is the formulation of betamethasone
which is most trialled.Compared to dexamethasone, betamethasone sodium
phosphate / acetate may reduce the risk of chorioamnionitis.
• Betamethasone is available in two formulations.
• Betamethasone sodium phosphate is soluble with a short half-life,
• while betamethasone sodium acetate is insoluble and has a long half-life.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Recommendation
Clinicians should be aware that betamethasone phosphate, the
preparation widely available in the UK, has different
pharmacokinetics from betamethasone sodium phosphate/acetate
mix and there is little evidence to guide the effective dosage regimen
for this formulation.

Oral or transplacental administration is not recommended

There is insufficient evidence to support administration by these routes

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 How long after administration is a course of antenatal corticosteroids most effective

• Recommendation
Antenatal corticosteroid use reduces neonatal death when the first dose is
given within 48 hours prior to birth

Benefits are also seen when the first dose is given within 24 hours of birth.
Antenatal corticosteroids should still be given if birth is expected within this
time

Antenatal corticosteroids are most effective in reducing respiratory distress

syndrome in pregnancies that birth between 24 hours and 7 days of
administration of the second dose of antenatal corticosteroids.
Evidence for Recommendations
Discussed in the World Health Organisation (WHO) Recommendations on
Interventions to Improve Preterm Birth Outcomes 2015 guidance that sites an
archived Cochrane review of randomised controlled trials.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 Risks associated with administration of antenatal corticosteroids

• Recommendation
Women should be counselled regarding the risks and
uncertainties surrounding the evidence of antenatal
corticosteroid treatment.

Institutions should use standard guidelines for the assessment and

management of neonatal hypoglycaemia in late preterm or
early term newborn who have received recent antenatal
corticosteroids.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 • Risk in woman

In the Cochrane Systematic review on antenatal corticosteroids for fetal lung maturity
there was no evidence that antenatal corticosteroids increased rates of maternal
infection.

• Corticosteroids are known to increase maternal blood glucose levels.

• Risk in baby

Affects fetal growth

• Higher rates of neonatal hypoglycaemia

• Long-term metabolic and neurological consequences of neonatal hypoglycaemia are

uncertain.

• Concerns about long-lasting effects on cardiovascular system and metabolic profile.

• May be detrimental effects on brain and long-term development, with higher risk of
psychiatric and behavioural disorders.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 What are the contraindications to the use of antenatal corticosteroids?

• Recommendation
Birth should not be delayed to administer antenatal
corticosteroids when there are serious concerns about maternal
or fetal condition that will be alleviated by expedited birth
In the presence of systemic infection, the potential beneficial
effects of antenatal corticosteroids intended for the baby are
balanced against the effect of exacerbating the severity of
systemic infection both for the woman and her baby.
Evidence for Recommendation:
Addressed in guidance from the WHO.
• Corticosteroids suppress the immune system. There is a risk that
their use may activate latent infections or exacerbate fungal
infections.In a woman with systemic infection, it may
theoretically suppress the immune response to the infection.
+91 9094 200 800 +447464245285 +447341981539 [email protected]
Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 In what circumstances should an antenatal course of corticosteroids be
repeated?

• Recommendation
Women should be informed that no reduction in serious morbidity or long-term
benefits have been seen with repeat corticosteroids.

• Babies who received repeat doses of antenatal corticosteroids are smaller

(lower birthweight and reduced length).

• There is currently limited evidence to recommend repeat courses of

antenatal corticosteroids if a woman remains at imminent risk of preterm
birth seven days after administration of antenatal corticosteroids.

• However, a further course may reduce the need for neonatal respiratory
support
The maximum number of corticosteroid courses given in any one
pregnancy should not exceed three.

+91 9094 200 800 +447464245285 +447341981539 [email protected]

Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]
 +91 9094 200 800 +447464245285 +447341981539 [email protected]
Visit us at www.studymrcog.com Contact: +91 9094 200 800 Email: [email protected]