Authors’ reply re: Antenatal magnesium sulphate for the
prevention of cerebral palsy in infants born preterm: a double-blind,
randomised, placebo-controlled, multi-centre trial
[Authors’ title] Time range for treatment with magnesium sulphate
We thank Larsen et al.1 for their interest in our
newly published randomised controlled trial on the use of magnesium
sulphate (MgSO4) for neuroprotection in preterm
birth.2 Larsen et al. argue that MgSO4should only be offered to women in imminent preterm birth at gestational
age (GA) below 32 weeks. Larsen et al. present the expected number
needed to treat. These numbers are based on Danish data and may not be
extrapolated to other countries.
Unlike the Cochrane review cited by Larsen et al.,3 an
updated meta-analysis, which included the results from our randomised
controlled trial, demonstrated a significantly decreased risk of
cerebral palsy (CP) in children exposed to antenatal
MgSO4 not only given before GA 28, but also before GA 32
weeks.4 It seems likely that the lack of statistically
significance at higher GAs is due to lack of power. Accordingly, the
main reason for recommending treatment prior to GA 32 is the increasing
number needed to treat with higher GA. This, together with the potential
and known adverse effects of MgSO4, must be weighed
against the consequences of CP for the child, family and society.
Based on the current evidence, we agree that MgSO4should be reserved for women in imminent preterm birth before GA 32
weeks due to the lower frequency of CP with higher GA. This
recommendation may, however, be revised when results of future studies
are ready, in particular from the
ongoing randomised controlled trial in women at imminent risk for
preterm delivery at GA 30 to 34 weeks.5
With regard to the lower limit for GA, the studies in our meta-analysis
only contain few, if any, infants born before GA 24 weeks. If the
foetus is considered viable and the woman is offered antenatal steroids
for fetal lung-maturation, it could be argued that MgSO4should also be an option despite the lack of scientific evidence. Due to
the expected higher rate of CP in infants born prior to GA 24 weeks and
anticipation of a similar effect of MgSO4 as that seen
at higher GA, the number needed to treat will most likely be lower than
for infants born at a higher GA.
Hanne Trap Wolf, Jesper Brok, Tine Brink Henriksen, Hanne Kristine
Hegaard, Gorm Greisen, Tom Weber, Ole Pryds, Jannie Dalby Salvig, Morten
Hedegaard, Anja Pinborg, and Lene Drasbek Huusom
1. Larsen M, Krebs L, Rackauskaite G, Hoei-Hansen C, Greisen G. Re:
Antenatal magnesium sulphate for the prevention of cerebral palsy in
infants born preterm: a double-blind, randomised, placebo-controlled,
multi-centre trial. (First comment letter, reference to be added).
2. Wolf HT, Brok J, Henriksen TB, Greisen G, Salvig JD, Pryds O, et al.
Antenatal magnesium sulphate for the prevention of cerebral palsy in
infants born preterm: a double-blind, randomised, placebo-controlled,
multi-centre trial. BJOG. 2020 Apr 1. doi: 10.1111/1471-0528.16239.
[Epub ahead of print]
3. Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium
sulphate for women at risk of preterm birth for neuroprotection of the
fetus. Cochrane database Syst Rev. 2009 Jan 21;(1):CD004661.
4. Wolf HT, Huusom LD, Henriksen TB, Hegaard HK, Brok J, Pinborg A.
Magnesium sulphate for foetal neuroprotection at imminent risk for
preterm delivery: a systematic review with meta-analysis and trial
sequential analysis. BJOG. 2020 Mar 31. doi: 10.1111/1471-0528.16238.
[Epub ahead of print]
5. Crowther CA, Middleton PF, Wilkinson D, Ashwood P, Haslam R, MAGENTA
Study Group. Magnesium sulphate at 30 to 34 weeks’ gestational age:
neuroprotection trial (MAGENTA)–study protocol. BMC Pregnancy
Childbirth. 2013 Apr 9;13:91.