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Childhood outcomes after maternal antenatal sildenafil treatment for severe early-onset fetal growth restriction: a randomized trial (STRIDER NZAus)

Journal of Perinatology volume 44, pages 396–403 (2024)Cite this article

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Abstract

In this follow-up at 2.5 years of children from the STRIDER NZAus Trial (N = 112), in which women with singleton pregnancies affected by severe early fetal growth restriction were randomized to sildenafil citrate 75 mg daily or placebo until 32 weeks, there was no difference between groups in survival without neurosensory impairment, defined as any of cerebral palsy, deafness, blindness, cognitive delay (Bayley III cognition or language score >1 SD below mean) or motor delay: 30/56[54%] vs. 34/56[61%]; aOR = 0.74, 95%CI: 0.31, 1.77. However, children exposed to sildenafil appeared to be more likely to have cognitive delay (13/45[29%] vs. 4/40[10%]; aOR = 3.71, 95% CI: 1.01, 13.63) but less likely to have emotional-behavioural difficulties (2/43[5%] vs. 8/38[21%]; aOR = 0.19, 95%CI: 0.03, 1.00). Conclusion: maternal sildenafil treatment for severe early-onset FGR was not associated with altered survival free of neurosensory impairment at 2.5 years’ corrected age.

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Fig. 1: Participant flow in STRIDER NZAus Childhood Outcome Study.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the women and children who participated in this study. The following were non-author contributors to this study: Frank Bloomfield, Liggins Institute, University of Auckland; John Thompson, Department of Pediatrics: Child and Youth Health, University of Auckland; Trecia Wouldes, Department of Psychological Medicine, University of Auckland; Janice Taylor, Auckland City Hospital; Helen Liley, Leith Poulsen, Jane Fox and Suzanne Bates, Mater Mothers’ Hospital, Brisbane; Marion McDonald, Royal Women’s Hospital, Melbourne; Lisa McKeown, Royal Brisbane and Women’s Hospital, Brisbane; Mei’En Lim, Safiyyah Abdul Aziz, Lori Gardiner, Emma Anderton and Carolyn Smargiassi, King Edward Memorial Hospital, Perth; Pat Ashwood, Ros Lontis, Women’s and Children’s Hospital, Adelaide; Di Leishman, Christchurch Women’s Hospital; Annemarie Lawrence, Townsville Hospital and Health Service, Townsville; Anne Lainchbury, The Royal Hospital for Women, Sydney; Gabrielle Pell, Elaine Kelly, Elisha Josev, Julianne Duff, Noni Davis and Anne-Marie Turner, Mercy Hospital for Women, Melbourne. We also acknowledge the investigators of the STRIDER NZAus Trial: Katie Groom and Joanna de Sousa, National Women’s Health, Auckland City Hospital; Glenn Gardener, Anne Tremellen, Bekki Cavallaro, Frances Maguire and Akina Kato, Mater Mothers’ Hospital, Brisbane; Julia Unterscheider and Stefan Kane, The Royal Women’s Hospital, Melbourne; Renuka Sekar, Lisa McKeown, Gillian Lack and Katie Foxcroft, Royal Brisbane and Women’s Hospital, Brisbane; Jan Dickinson and Paula Carter, King Edward Memorial Hospital, Perth; Peter Muller, Pat Ashwood and Andrea Deussen, Women’s and Children’s Hospital, Adelaide; Rosemary Reid, Christchurch Women’s Hospital; David Watson, Audra Davis and Cherie Boniface, Townsville Hospital and Health Service, Townsville; Antonia Shand, Alec Welsh and Anne Lainchbury, The Royal Hospital for Women, Sydney; Jaynana Marlow, Madeline Dymond-Cate and Trish Burke, Wellington Hospital; Susan Walker and Gabrielle Pell, Mercy Hospital for Women, Melbourne; Jon Hyett and Jane Tooher, Royal Prince Alfred Hospital, Sydney; Jonathan Morris and Kathryn Austin, Royal North Shore Hospital, Sydney.

Funding

Cure Kids, Auckland, New Zealand (3570); Royal Australian and New Zealand College of Obstetricians and Gynaecologists Te Kāhui Oranga ō Nuku Mercia Barnes Trust (3703775); Auckland Medical Research Foundation (1117001); Neurological Foundation of New Zealand (1708-PG); University of Auckland (FRDF 3714288); Leadership Fellowship, National Health and Medical Research Council of Australia (2016390). The funders had no role in study design, analysis and interpretation of data, or in the decision to publish.

Author information

Authors and Affiliations

  1. Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand

    Christopher J. D. McKinlay

  2. Kidz First Neonatal Care, Counties Manukau Health, Auckland, New Zealand

    Christopher J. D. McKinlay

  3. Women’s and Children’s Hospital, Adelaide, SA, Australia

    Chad Anderson

  4. Royal Women’s Hospital, Melbourne, VIC, Australia

    Jeanie L. Y. Cheong

  5. Clinical Sciences, Murdoch Children’s Research Institute, Melbourne, VIC, Australia

    Jeanie L. Y. Cheong

  6. Obstetrics and Gynaecology, University of Melbourne, Melbourne, VIC, Australia

    Jeanie L. Y. Cheong

  7. Royal Prince Alfred Hospital, Sydney, NSW, Australia

    Adrienne Gordon

  8. University of Otago, Christchurch, New Zealand

    Sarah L. Harris

  9. Te Whatu Ora Waitaha, Christchurch, New Zealand

    Sarah L. Harris

  10. Mater Mothers’ Hospital, Brisbane, QLD, Australia

    Elizabeth M. Hurrion

  11. Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia

    Elizabeth M. Hurrion

  12. Townsville University Hospital, Townsville, QLD, Australia

    Susan Ireland

  13. Royal Brisbane & Women’s Hospital, Brisbane, QLD, Australia

    Pieter Koorts

  14. School of Clinical Medicine, University of New South Wales, Sydney, Australia

    Kei Lui

  15. Liggins Institute, University of Auckland, Auckland, New Zealand

    Laura Mackay, Mariska Oakes-Ter Bals & Katie M. Groom

  16. Mercy Hospital for Women, Melbourne, VIC, Australia

    Gillian Opie

  17. King Edward Memorial Hospital, Perth, WA, Australia

    Mary Sharp

  18. University of Western Australia, Perth, WA, Australia

    Mary Sharp

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Contributions

Conception and design: CJDM, KMG, and LM; Supervision and oversight: CJDM, KMG, LM, and MO-TB; Funding: CJDM, KMG, and LM; Data collection and processing: CJDM, CA, JLYC, AG, SLH, EH, SI, PK, KL, LM, MO-TB, GO, MS, and KMG. Analysis and interpretation of data: CJDM, KMG, and LM. Drafting of manuscript: CJDM, KMG, LM. Critical review and approval of final version: All authors.

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Correspondence to Christopher J. D. McKinlay or Katie M. Groom.

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McKinlay, C.J.D., Anderson, C., Cheong, J.L.Y. et al. Childhood outcomes after maternal antenatal sildenafil treatment for severe early-onset fetal growth restriction: a randomized trial (STRIDER NZAus). J Perinatol 44, 396–403 (2024). https://doi.org/10.1038/s41372-023-01838-7

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