Prenatal Intravenous Magnesium at 30-34 Weeks’ Gestation and Neurodevelopmental Outcomes in Offspring
Authors: Crowther Caroline A. , Ashwood Pat , Middleton Philippa F. , McPhee Andrew , Tran Thach , Harding Jane E. ,   MAGENTA Study Group, Alsweiler Jane , Baker Ella , Eaglen Deb , Groom Katie , Hauch Helga , Mackay Laura , Pacella Marisa J. , Preest Alisha , Taylor Janice , Williamson Katherine , Tottman Anna , Austin Nicola , Darlow Brian A. , Dixon Bronwyn , Ellis Nicola , Graham Patricia , Gullam Joanna , Leishman Dianne , Van Dyk Michelle M. , Broadbent Roland , Dawson Pauline , Devenish Celia , Douglas Janene , McCaffrey Frances , Carey Robert , Marshall Peter , Morris Scott , Nguyen Tran , Gaerty Kirsten , Grupp Oliver , Boddice Geoffrey , Green Ann , Mahomed Kassam , Turner Laura , Baldwin Michelle , Dennis Amanda , Fisher Eleanor , Gee Karen , Gee Michael , Strong David , Asadi Sharin , Burakevych Nataliia , Griffth Rebecca , Kendaragama Anushika , Ksionda Olga , Kurkchi Khansaa , Paine Claudia , Philipsen Sarah , Rogers Jenny , Samuel Debbie , Shah Rajesh , Slabkevich Nina , Stewart Heather , Vasilenko Alena , Beckman Michael , Bolton Elize , Chaplin Jacqueline , Cooper Catherine , Fox Jane , Gray Peter , Hawley Glenda , Hickey Julie , Hoey Joanne , Hurrion Elizabeth , Jardine Luke , Kan Janet , Lynn Lisa , McHale Teoni , Poad Dianne , Poulsen Leith , Warhurst Kym , Bice Caitlin , Davis Noni , Duff Julanne , Jones Amanda , Kelly Elaine A. , Magrath Emma , Malcolm Dianne , O'Connor Kerry-Ann , Opie Gillian , Turner Anne-Marie , Walker Susan , Williamson Amanda , Woods Heather , Hou David , Kippen Michella , Schroder Jen , Thesing Avril J. , Wadsworth Sarah , Camadoo Laxmi , Dyer Christine , Jones Stephanie , Kothari Alka , Markovic Vesna , Owens Jenny , Shallcross Meredith , Butterley Karen , Davis Caroline , De Paoli Antonio , Dodson Serani , Holmes Matthew , Kenchapla Hanumesha , Matzolic Tammy , McGregor Amy , Patel Sajid , Simic Samja , Andrijic Vanessa , Biggs Vikki , Brandrick Susan , Goldstein Silvia , Lainchbury Anne , Lui Kei , Lyons Sarah , Shand Antonia , Sutton Lee , Barnes Lynette , Bowen Jennifer , Harvey Lyndsey , Jacobs Claire , Milligan Jill , Morris Jonathan , Nippita Tanya , Sau-Harvey Rachelle , Sparks Amy , Wegener Anmaree , Burnett Alice , Callanan Kate , Cheong Jeanie , De Luca Cinzia , Doyle Lex , du Plessis Jacobus , Duff Julianne , Hutchinson Esther , Kane Stefan C. , Kelly Elaine , Kornman Louise , Maxwell Dianna , McDonald Marion , Poth Megan , Arcus James C. , Cruickshank Marie , Devoy Bridget , Fanning Melanie J. , Henriksen Kylee , Morse Fiona , Schiller Amber , Tomlinson Paul A. , Davis Greg , Dosen Ana , Roberts Lynne , Rowe Clare , Creen Julie , Gee Kellee , Hurley Tom , Pallett Linda , Smitheram Carmel , Thompson Annette , Weaver Edward , Lynch Lee-anne , Pszczola Rosalynn , Said Joanne , Shekleton Julianne , Craine Karina , Fergus Judy , Ford Jo , Harris Annette , Kummer Megan , Thurnell Chris , Boniface Cherie , Davis Audra , Dickinson Corrinne , Ireland Susan , Lawrence Annemarie , Mandell Katie , Menon Sheree , Watson David , Bennett Michelle , Elder Rose , Hayne Philippa , Massov Lorna , Miller Helen , Sandler Meghan E. , Schenk Valerie , Wilkes Natalie , Sibanda Thabani , Davis Warren , Dill Natalie , Espinoza Nelson , Kunjunju Ansar , Wright Ian , Anderson Chad , Ball Vincent , Bhatia Vineesh , Burford-Rice Rose , Gagliardi Daniela , Gooding Michaela L. , Han Shanshan , Headley Bevan , Holst Caroline , Keir Amy , Khong Tech Yee , Kochar Anuradha , Lai Yin Yee , Paleologos Mary , Robinson Jeffrey , Robinson Kaye , Stark Michael , Thompson Elise , Willet Miranda , Zhang Yu 
Published: August 2023

Importance

Intravenous magnesium sulfate administered to pregnant individuals before birth at less than 30 weeks’ gestation reduces the risk of death and cerebral palsy in their children. The effects at later gestational ages are unclear.

Objective

To determine whether administration of magnesium sulfate at 30 to 34 weeks’ gestation reduces death or cerebral palsy at 2 years.

Design, Setting, and Participants

This randomized clinical trial enrolled pregnant individuals expected to deliver at 30 to 34 weeks’ gestation and was conducted at 24 Australian and New Zealand hospitals between January 2012 and April 2018.

Intervention

Intravenous magnesium sulfate (4 g) was compared with placebo.

Main Outcomes and Measures

The primary outcome was death (stillbirth, death of a live-born infant before hospital discharge, or death after hospital discharge before 2 years’ corrected age) or cerebral palsy (loss of motor function and abnormalities of muscle tone and power assessed by a pediatrician) at 2 years’ corrected age. There were 36 secondary outcomes that assessed the health of the pregnant individual, infant, and child.

Results

Of the 1433 pregnant individuals enrolled (mean age, 30.6 [SD, 6.6] years; 46 [3.2%] self-identified as Aboriginal or Torres Strait Islander, 237 [16.5%] as Asian, 82 [5.7%] as Māori, 61 [4.3%] as Pacific, and 966 [67.4%] as White) and their 1679 infants, 1365 (81%) offspring (691 in the magnesium group and 674 in the placebo group) were included in the primary outcome analysis. Death or cerebral palsy at 2 years’ corrected age was not significantly different between the magnesium and placebo groups (3.3% [23 of 691 children] vs 2.7% [18 of 674 children], respectively; risk difference, 0.61% [95% CI, −1.27% to 2.50%]; adjusted relative risk [RR], 1.19 [95% CI, 0.65 to 2.18]). Components of the primary outcome did not differ between groups. Neonates in the magnesium group were less likely to have respiratory distress syndrome vs the placebo group (34% [294 of 858] vs 41% [334 of 821], respectively; adjusted RR, 0.85 [95% CI, 0.76 to 0.95]) and chronic lung disease (5.6% [48 of 858] vs 8.2% [67 of 821]; adjusted RR, 0.69 [95% CI, 0.48 to 0.99]) during the birth hospitalization. No serious adverse events occurred; however, adverse events were more likely in pregnant individuals who received magnesium vs placebo (77% [531 of 690] vs 20% [136 of 667], respectively; adjusted RR, 3.76 [95% CI, 3.22 to 4.39]). Fewer pregnant individuals in the magnesium group had a cesarean delivery vs the placebo group (56% [406 of 729] vs 61% [427 of 704], respectively; adjusted RR, 0.91 [95% CI, 0.84 to 0.99]), although more in the magnesium group had a major postpartum hemorrhage (3.4% [25 of 729] vs 1.7% [12 of 704] in the placebo group; adjusted RR, 1.98 [95% CI, 1.01 to 3.91]).

Conclusions and Relevance

Administration of intravenous magnesium sulfate prior to preterm birth at 30 to 34 weeks’ gestation did not improve child survival free of cerebral palsy at 2 years, although the study had limited power to detect small between-group differences.

Trial Registration

anzctr.org.au Identifier: ACTRN12611000491965