TY - JOUR
T1 - Perinatal adversities in tuberous sclerosis complex
T2 - determinants and neurodevelopmental outcomes
AU - Tuberous Sclerosis 2000 Study Group
AU - Zhang, Alexa X.D.
AU - Liang, Holan
AU - McEwen, Fiona S.
AU - Tye, Charlotte
AU - Woodhouse, Emma
AU - Underwood, Lisa
AU - Shephard, Elizabeth
AU - Sheerin, Fintan
AU - Bolton, Patrick F.
N1 - Funding Information:
Members of the Tuberous Sclerosis 2000 Study Group are as follows: V Attard, A Clarke, FV Elmslie, AK Saggar, St George's Hospital, London; D Baines, BA Kerr, Royal Manchester Children's Hospital, Manchester; N Higgins, Department of Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge; C Brayne, Institute of Public Health, University of Cambridge; I Carcani‐Rathwell, C Connolly, M Clifford, A Lydon, F Oluwo, H Rogers, C Srivastava, J Steenbruggen, Institute of Psychiatry, Psychology & Neuroscience, King's College London; JA Cook, Sheffield Children's Hospital, Sheffield; C Falconer, St James's University Hospital, Leeds; DM Davies, JR Sampson, Institute of Medical Genetics, Cardiff; AE Fryer, Alder Hey Children's Hospital, Liverpool; M Haslop, Y Granader, University of Cambridge (currently at Yeshiva University, New York); PD Griffiths, University of Sheffield; A Hunt, Tuberous Sclerosis Association, London; WWK Lam, Western General Hospital, Edinburgh; JC Kingswood, Royal Sussex County Hospital, Brighton; ZH Miedzybrodzka, College of Life Sciences and Medicine, Aberdeen; H Crawford, PJ Morrison, Belfast City Hospital; FJK O'Callaghan, Great Ormond Street Hospital/Institute of Child Health, University College London; SG Philip, Birmingham Children's Hospital, Birmingham; S Seri, Aston Brain Centre, School of Life and Health Sciences, Aston University, Birmingham; R Sheehan‐Dare, The General Infirmary, Leeds; CH Shepherd, Craigavon Area Hospital, Craigavon, UK. We thank all of the families for their time and help with this study. We thank Sanqian Zhang (Department of Statistics, Harvard University) for her help with statistics. This research was supported by grants from Action Medical Research (GN2301), Autism Speaks (#7696), Tuberous Sclerosis Association, and fellowships awarded to Holan Liang and Charlotte Tye from the UK Tuberous Sclerosis Association. The study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and an NIHR Senior Investigator Award to Patrick F. Bolton (PB NF‐SI‐0510‐10268). The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. The authors have stated that they had no interests that might be perceived as posing a conflict or bias.
Funding Information:
Members of the Tuberous Sclerosis 2000 Study Group are as follows: V Attard, A Clarke, FV Elmslie, AK Saggar, St George's Hospital, London; D Baines, BA Kerr, Royal Manchester Children's Hospital, Manchester; N Higgins, Department of Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge; C Brayne, Institute of Public Health, University of Cambridge; I Carcani-Rathwell, C Connolly, M Clifford, A Lydon, F Oluwo, H Rogers, C Srivastava, J Steenbruggen, Institute of Psychiatry, Psychology & Neuroscience, King's College London; JA Cook, Sheffield Children's Hospital, Sheffield; C Falconer, St James's University Hospital, Leeds; DM Davies, JR Sampson, Institute of Medical Genetics, Cardiff; AE Fryer, Alder Hey Children's Hospital, Liverpool; M Haslop, Y Granader, University of Cambridge (currently at Yeshiva University, New York); PD Griffiths, University of Sheffield; A Hunt, Tuberous Sclerosis Association, London; WWK Lam, Western General Hospital, Edinburgh; JC Kingswood, Royal Sussex County Hospital, Brighton; ZH Miedzybrodzka, College of Life Sciences and Medicine, Aberdeen; H Crawford, PJ Morrison, Belfast City Hospital; FJK O'Callaghan, Great Ormond Street Hospital/Institute of Child Health, University College London; SG Philip, Birmingham Children's Hospital, Birmingham; S Seri, Aston Brain Centre, School of Life and Health Sciences, Aston University, Birmingham; R Sheehan-Dare, The General Infirmary, Leeds; CH Shepherd, Craigavon Area Hospital, Craigavon, UK. We thank all of the families for their time and help with this study. We thank Sanqian Zhang (Department of Statistics, Harvard University) for her help with statistics. This research was supported by grants from Action Medical Research (GN2301), Autism Speaks (#7696), Tuberous Sclerosis Association, and fellowships awarded to Holan Liang and Charlotte Tye from the UK Tuberous Sclerosis Association. The study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and an NIHR Senior Investigator Award to Patrick F. Bolton (NF-SI-0510-10268). The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. The authors have stated that they had no interests that might be perceived as posinpg a conflict or bias.
Publisher Copyright:
© 2022 Mac Keith Press.
PY - 2022/10
Y1 - 2022/10
N2 - Aim: To examine the association between perinatal adversities and neurodevelopmental outcome in tuberous sclerosis complex (TSC). Method: The Tuberous Sclerosis 2000 study is a prospective, longitudinal UK study of TSC. In phase 1, mutation type, TSC family history, tuber characteristics, presence of cardiac rhabdomyomas, seizure characteristics, and intellectual ability were assessed in 125 children affected with TSC (64 females, 61 males; median age 39mo, range 4–254). In phase 2, 88 participants (49 females, 39 males; median age 148mo, range 93–323) were assessed for neurodevelopmental outcomes including intellectual ability, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Perinatal histories of 88 participants with TSC and 80 unaffected siblings were collected retrospectively using the Obstetric Enquiry Schedule and coded with a modified Gillberg Optimality Scale to measure levels of perinatal adversity. Data were analysed using Mann–Whitney U tests, Spearman's rank correlation, and linear regression with robust standard errors. Results: Children with familial TSC experienced significantly greater perinatal adversity than unaffected siblings. Perinatal adversity was higher in children with TSC-affected mothers than those with unaffected mothers. There was no significant association between perinatal adversities and neurodevelopmental outcomes after controlling for confounders. Interpretation: Maternal TSC is a significant marker of elevated perinatal risk in addition to risks incurred by fetal genotype. Pregnancies complicated by maternal or fetal TSC require higher vigilance, and mechanisms underlying increased perinatal adversity require further research. What this paper adds: Higher perinatal adversity is associated with familial tuberous sclerosis complex (TSC). Maternal TSC was associated with higher frequencies of several perinatal risk markers. Paternal TSC was not associated with higher levels of perinatal adversity. Perinatal adversity levels in TSC1 and TSC2 subgroups did not differ significantly. Perinatal adversities were not associated with neurodevelopmental outcomes.
AB - Aim: To examine the association between perinatal adversities and neurodevelopmental outcome in tuberous sclerosis complex (TSC). Method: The Tuberous Sclerosis 2000 study is a prospective, longitudinal UK study of TSC. In phase 1, mutation type, TSC family history, tuber characteristics, presence of cardiac rhabdomyomas, seizure characteristics, and intellectual ability were assessed in 125 children affected with TSC (64 females, 61 males; median age 39mo, range 4–254). In phase 2, 88 participants (49 females, 39 males; median age 148mo, range 93–323) were assessed for neurodevelopmental outcomes including intellectual ability, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Perinatal histories of 88 participants with TSC and 80 unaffected siblings were collected retrospectively using the Obstetric Enquiry Schedule and coded with a modified Gillberg Optimality Scale to measure levels of perinatal adversity. Data were analysed using Mann–Whitney U tests, Spearman's rank correlation, and linear regression with robust standard errors. Results: Children with familial TSC experienced significantly greater perinatal adversity than unaffected siblings. Perinatal adversity was higher in children with TSC-affected mothers than those with unaffected mothers. There was no significant association between perinatal adversities and neurodevelopmental outcomes after controlling for confounders. Interpretation: Maternal TSC is a significant marker of elevated perinatal risk in addition to risks incurred by fetal genotype. Pregnancies complicated by maternal or fetal TSC require higher vigilance, and mechanisms underlying increased perinatal adversity require further research. What this paper adds: Higher perinatal adversity is associated with familial tuberous sclerosis complex (TSC). Maternal TSC was associated with higher frequencies of several perinatal risk markers. Paternal TSC was not associated with higher levels of perinatal adversity. Perinatal adversity levels in TSC1 and TSC2 subgroups did not differ significantly. Perinatal adversities were not associated with neurodevelopmental outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85133849151&partnerID=8YFLogxK
U2 - 10.1111/dmcn.15224
DO - 10.1111/dmcn.15224
M3 - Article
C2 - 35366331
AN - SCOPUS:85133849151
SN - 0012-1622
VL - 64
SP - 1237
EP - 1245
JO - Developmental Medicine and Child Neurology
JF - Developmental Medicine and Child Neurology
IS - 10
ER -