preterm birth Flashcards
How/ Why does magnesium sulphate result in neuroprotection ?
not fully understood, likely multifactorial
- Magnesium sulphate reduces neuronal injury by ‘down regulation’ of excitatory stimuli. Damaged neurons are sensitive to the excitatory neurotransmitter glutamate, but the blocking of N-methyl-D-aspartate (NMDA) receptors by magnesium prevents the influx of calcium that causes cell death.
- Increased cerebral blood flow due to cerebral vasodilatation, thus minimising hypoxic-ischaemic damage.
- In an inflammatory model of preterm birth inducing pro-inflammatory cytokines, magnesium sulphate has been shown to prevent neuronal injury.
- Magnesium may have anti-apoptotic (programmed cell death) effects
What are the risk factors for CP?
Risks
PTB (less then 34 weeks)
VLWB (less the 1500g)
Also chorioamnionitis, APH, complications of multiples, placental insufficiency and perinatal asphyxia
Neonatal risk factors (inversely associated with gestational age)
IVH
Periventricular leucomalacia
Cochrane review for neuroprotection is a landmark trial
Structure of the review:
Purpose of the review?
How many trials involved?
What was the objectives of the trial?
How many woman?
The objectives of the Cochrane review were to assess the efficacy and safety of magnesium sulphate as a fetal neuroprotective agent for women at risk of preterm birth.
The review encompassed all five trials, thereby involving 6145 pregnancies in which women at risk of preterm birth at less than 34 weeks gestation were randomised to either magnesium sulphate or placebo.
A further subgroup analysis was performed involving those trials which had used magnesium sulphate for ‘neuroprotection intention only’. This involved four trials and 4446 children, having excluded the MAGPIE Trial and a subset of patients receiving magnesium sulphate for tocolysis in MagNET.
What was the findings of the cochrane review for neuroprotection?
The primary outcome (paediatric) was the composite outcome of death, severe neurological impairment (cerebral palsy, neurodevelopmental delay, blindness and deafness), or both.
1 MORTALITY – NO INCREASE
2 CEREBRAL PALSY – SIGNIFICANTLY REDUCED
RR 0.7
5% (placebo) to 3.4% (MgSO4) Reduction in risk 1.6% NNT 63 (NNT under 28 weeks 29)
A similar magnitude of risk reduction was seen for moderate to severe cerebral palsy (RR 0.64; 95% CI 0.44-0.92) and substantial gross motor dysfunction (RR 0.61; 95% CI 0.44-0.85).
Combined mortality and neurological outcomes
Although there was no significant effect for the composite outcome when all five trials were included (RR 0.94; 95% CI 0.78-1.12), there was a significant reduction among those given magnesium with neuroprotective intent (RR 0.85; 95% CI 0.74-0.98).
ii. Maternal outcomes
There were no significant differences observed for the major maternal outcomes of death (RR 1.25; 95% CI 0.51-3.07), cardiac arrest (RR 0.34; 95% CI 0.04-3.26) or respiratory arrest (RR 1.02; 95% CI 0.06-16.25). Significantly more women ceased therapy in the magnesium group (RR 3.26; 95% CI 2.46-3.51). Of secondary maternal outcomes, magnesium therapy was associated with significantly more hypotension (RR 1.51; 95% CI 1.09-2.09) and tachycardia (RR 1.53, 95% CI 1.03-2.29).
How do you give MgSO4 to? and how? and when?
for neuroprotection
In women at risk of early preterm imminent birth, use magnesium sulphate for neuroprotection of the fetus, infant and child:
when gestational age is less than 30 weeks.
when early preterm birth is planned or definitely expected within 24 hours. (When birth is planned, commence magnesium sulphate as close to four hours before birth as possible).
regardless of plurality (number of babies in utero).
regardless of the reason women (at less than 30 weeks’ gestation) are considered to be at risk of preterm birth.
regardless of parity (number of previous births for the woman).
regardless of anticipated mode of birth.
whether or not antenatal corticosteroids have been given
intravenously with a 4 gram loading dose (slowly over 20-30 minutes) and 1 gram per hour maintenance dose via intravenous route, with no immediate repeat doses. Continue regimen until birth or for 24 hours, whichever comes first.
what is the rate of PTB before 30 weeks?
1.2%
What is the benefit of steroids?
Benefits of corticosteroids Reduced perinatal mortality -4%, NNT 23 No change in fetal death Significant reduction in neonatal death
RDS
-9% NNT 13
27% reduction in the need for respiratory support
Reduced respiratory support needed by 1.5 days
Reduced mean duration of oxygen supplementation by almost 3 days
No difference in chronic lung disease, surfactant use and air leak syndrome
Reduce risk ICH
-5% NNT 21
Severe ICH RR 12% NNT 8
Necrotising enterocolitis
Significantly reduced absolute risk reduction 3% NNT 29
Systemic infection within 48 hours after birth
Absolute risk reduction 4% NNT 28
No difference in SGA, birthweight, apgars, admission to NICU, length of neonatal hospitalisation
What si the benefit of repeat dosing of steroids?
Is the harm?
There is no benefit of the steroids when the baby is born 7 days or more after they are given Benefits No difference in perinatal death with repeat dosing Reduction in RDS Risk reduction 6% NNT 16 Reduction in ventilation NNT 16 –5% Oxygen supplementation Surfactant use NNT 21 –5% Inotropic support NNT 22 RRR 5%
Serious neonatal outcomes (all cause)
significantly reduced
Reduces risk of patent ductus arteriosis
No difference in IVH with repeat dosing
Risks
Did not increase maternal infection
More likely to experience insomnia
Repeated dosing is associated with a reduction in a number of body measurements a birth but no difference in being SGA and by hospital discharge no difference in weights
No difference in childhood mortality
No difference in disability and impairment
How to choose between betamethasone and dexamethasone?
Betamethasome
Less periventricular leukomalacia (cochrane)
Oral increases ICV and neonatal sepsis so give IM
Dexamethasone has a better RR then betamethasone for ICH prevention (cochrane)
RCOG says either is ok
