scholarly journals Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal Thyroid Function on Child Behavior

2019 ◽  
Vol 105 (3) ◽  
pp. e417-e427 ◽  
Author(s):  
Charlotte Hales ◽  
Peter N Taylor ◽  
Sue Channon ◽  
Kirsten McEwan ◽  
Anita Thapar ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Effect Size ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Thyroid Screening ◽  
Child Cognition ◽  
Child Adhd ◽  
The Social ◽  
Child Neurodevelopment ◽  
The Uk

Abstract Context & Objectives The Controlled Antenatal Thyroid Screening (CATS) study was the first randomized controlled trial to investigate effects of treating suboptimal gestational thyroid function (SGTF) on child cognition. Since observational studies indicated that SGTF may also increase symptoms of autism and attention-deficit/hyperactivity disorder (ADHD), the CATS cohort was used to investigate whether treatment of mothers affected their children’s behavior. Design & Participants Mothers (N = 475) completed 3 questionnaires: the Strengths and Difficulties Questionnaire (SDQ), the Child ADHD Questionnaire, and the Social Communication Questionnaire (SCQ, used as a screen for autism spectrum disorder [ASD]), about their children (mean age 9.5 years). Group comparisons of total scores, numbers of children above clinical thresholds, and association between high maternal free thyroxine (FT4) (> 97.5th percentile of the UK cohort, “overtreated”) and child neurodevelopment were reported. Results There were no differences in total scores between normal gestational thyroid function (GTF) (n = 246), treated (n = 125), and untreated (n = 104) SGTF groups. More children of treated mothers scored above clinical thresholds, particularly the overtreated. Scores were above thresholds in SDQ conduct (22% vs 7%), SCQ total scores (7% vs 1%), and ADHD hyperactivity (17% vs 5%) when comparing overtreated (n = 40) and untreated (N = 100), respectively. We identified significantly higher mean scores for SDQ conduct (adjusted mean difference [AMD] 0.74; 95% confidence interval [CI], 0.021-1.431; P = 0.040, effect size 0.018) and ADHD hyperactivity (AMD 1.60, 95% CI, 0.361-2.633; P = 0.003, effect size 0.028) comparing overtreated with normal-GTF children. Conclusions There was no overall association between SGTF and offspring ADHD, ASD, or behavior questionnaire scores. However, children of “overtreated” mothers displayed significantly more ADHD symptoms and behavioral difficulties than those of normal-GTF mothers. Thyroxine supplementation during pregnancy requires monitoring to avoid overtreatment.

scholarly journals CATS II Long-term Anthropometric and Metabolic Effects of Maternal Sub-optimal Thyroid Function in Offspring and Mothers

2020 ◽  
Vol 105 (7) ◽  
pp. 2150-2161 ◽  
Author(s):  
Ilaria Muller ◽  
Peter N Taylor ◽  
Rhian M Daniel ◽  
Charlotte Hales ◽  
Anna Scholz ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Fat Mass ◽  
Augmentation Index ◽  
Controlled Trial ◽  
Aortic Pulse Wave Velocity ◽  
Thyroid Stimulating Hormone ◽  
Metabolic Effects ◽  
Long Term Effects ◽  
Thyroid Screening

Abstract Context and Objectives The Controlled Antenatal Thyroid Screening Study I (CATS-I) was a randomized controlled trial investigating the effects of levothyroxine therapy for suboptimal gestational thyroid function (SGTF), comparing outcomes in children of treated (SGTF-T) with untreated (SGTF-U) women during pregnancy. This follow-up study, CATS-II, reports the long-term effects on anthropometric, bone, and cardiometabolic outcomes in mothers and offspring and includes a group with normal gestational thyroid function (NGTF). Design & Participants 332 mothers (197 NGTF, 56 SGTF-U, 79 SGTF-T) aged 41.2±5.3 years (mean±SD) and 326 paired children assessed 9.3±1.0 years after birth for (i) body mass index (BMI); (ii) lean, fat, and bone mass by dual-energy X-ray absorptiometry; (iii) blood pressure, augmentation index, and aortic pulse-wave-velocity; and (iv) thyroid function, lipids, insulin, and adiponectin. The difference between group means was compared using linear regression. Results Offspring’s measurements were similar between groups. Although maternal BMI was similar between groups at CATS-I, after 9 years (at CATS-II) SGTF-U mothers showed higher BMI (median [interquartile ratio] 28.3 [24.6-32.6] kg/m2) compared with NGTF (25.8 [22.9-30.0] kg/m2; P = 0.029), driven by fat mass increase. At CATS-II SGTF-U mothers also had higher thyroid-stimulating hormone (TSH) values (2.45 [1.43-3.50] mU/L) than NGTF (1.54 [1.12-2.07] mU/L; P = 0.015), since 64% had never received levothyroxine. At CATS-II, SGTF-T mothers had BMI (25.8 [23.1-29.8] kg/m2, P = 0.672) and TSH (1.68 [0.89-2.96] mU/L; P = 0.474) values similar to NGTF mothers. Conclusions Levothyroxine supplementation of women with SGTF did not affect long-term offspring anthropometric, bone, and cardiometabolic measurements. However, absence of treatment was associated with sustained long-term increase in BMI and fat mass in women with SGTF.

scholarly journals Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal Thyroid Function on Child Cognition

2018 ◽  
Vol 103 (4) ◽  
pp. 1583-1591 ◽  
Author(s):  
Charlotte Hales ◽  
Peter N Taylor ◽  
Sue Channon ◽  
Ruth Paradice ◽  
Kirsten McEwan ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Thyroid Screening ◽  
Child Cognition

scholarly journals Good participatory practice for coronavirus disease 2019 (COVID-19) research: the case of a COVID-19 prevention study

2021 ◽  
Vol 6 ◽  
pp. 216
Author(s):  
Carlo Perrone ◽  
William Schilling ◽  
James J. Callery ◽  
Elizabeth A. Ashley ◽  
Mary Chambers ◽  
...  
Keyword(s):  
Ethical Issues ◽  
Controlled Trial ◽  
Double Blind ◽  
Balance Study ◽  
Healthcare Facilities ◽  
The Social ◽  
Information Materials ◽  
Context Specific ◽  
The Uk ◽  
Fine Tune

Background: The COPCOV study (chloroquine/ hydroxychloroquine prevention of coronavirus disease), which started recruitment in April 2020, is a multi-country double-blind, randomised, placebo-controlled trial which is being conducted in healthcare facilities involved in COVID-19 case management. COPCOV aims to recruit healthcare workers and other staff employed in facilities managing people with proven or suspected COVID-19. Methods: We conducted a series of engagement sessions, each involving a short presentation of the study, a section where attendees were asked to express if they would be interested in participating in such a study and which information they would need to change their view and an open Q&A section. Answers were transcribed and coded into themes by two independent investigators. Themes were derived from the data. The aims were to assess the feasibility of the study at the respective sites, to identify context-specific ethical issues, to understand concerns potential participants might have, to fine tune research procedures and to refine COPCOV information materials. They complemented other site-specific engagement, communication and public relation activities such as press releases and websites. Results: From 16th March 2020 to 20th January 2021, 12 engagement sessions were conducted in Thailand, Laos, Vietnam, Nepal and the UK involving 213 attendees in total. The sessions were designed to encourage potential participants and research professionals not directly involved in the project to interact with those who planned the study and those conducting it. Many attendees were keen to join the study while others had concerns. Questions raised revolved around the social value and study rationale; safety of trial medications and risk-benefit balance; study design and commitments. Conclusions: These sessions helped us refine information materials, identify misunderstandings about the study as well as complement site feasibility assessments. Our experience strongly supports the use of participatory practices prior to conducting clinical trials.

scholarly journals Good participatory practice for coronavirus disease 2019 (COVID-19) research: the case of a COVID-19 prevention study

2021 ◽  
Vol 6 ◽  
pp. 216
Author(s):  
Carlo Perrone ◽  
William Schilling ◽  
James J. Callery ◽  
Elizabeth A. Ashley ◽  
Mary Chambers ◽  
...  
Keyword(s):  
Ethical Issues ◽  
Controlled Trial ◽  
Double Blind ◽  
Balance Study ◽  
Healthcare Facilities ◽  
The Social ◽  
Information Materials ◽  
Context Specific ◽  
The Uk ◽  
Fine Tune

Background: The COPCOV study (chloroquine/ hydroxychloroquine prevention of coronavirus disease), which started recruitment in April 2020, is a multi-country double-blind, randomised, placebo-controlled trial which is being conducted in healthcare facilities involved in coronavirus disease 2019 (COVID-19) case management. COPCOV aims to recruit healthcare workers and other staff employed in facilities managing people with proven or suspected COVID-19. Methods: We conducted a series of engagement sessions, each involving a short presentation of the study, a section where attendees were asked to express if they would be interested in participating in such a study and which information they would need to change their view and an open Q&A section. Answers were transcribed and coded into themes by two independent investigators. Themes were derived from the data. The aims were to assess the feasibility of the study at the respective sites, to identify context-specific ethical issues, to understand concerns potential participants might have, to fine tune research procedures and to refine COPCOV information materials. They complemented other site-specific engagement, communication and public relation activities such as press releases and websites. Results: From 16th March 2020 to 20th January 2021, 12 engagement sessions were conducted in Thailand, Laos, Vietnam, Nepal and the UK involving 213 attendees in total. The sessions were designed to encourage potential participants and research professionals not directly involved in the project to interact with those who planned the study and those conducting it. Many attendees were keen to join the study while others had concerns. Questions raised revolved around the social value and study rationale; safety of trial medications and risk-benefit balance; study design and commitments. Conclusions: These sessions helped us refine information materials, identify misunderstandings about the study as well as complement site feasibility assessments. Our experience strongly supports the use of participatory practices prior to conducting clinical trials.

scholarly journals Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yasuhiko Kato ◽  
Hitoshi Kuwabara ◽  
Takashi Okada ◽  
Toshio Munesue ◽  
Seico Benner ◽  
...  
Keyword(s):  
Effect Size ◽  
Neural Plasticity ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Medium Effect ◽  
Double Blind ◽  
Parallel Group ◽  
Core Symptoms

Abstract Background Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods The current study explored metabolites representing the molecular mechanisms of oxytocin’s efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. Results Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR = 0.004, d = 1.13, N = 60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR = 0.006, r = − 0.485, N = 43) and deteriorations between 2 and 4 weeks (PFDR = 0.032, r = 0.415, N = 37). Limitations The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. Conclusion Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy. Trial registration: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264).

Oxytocin-Induced Increase in N,N-dimethylglycine and Time-Course of Changes in Oxytocin Efficacy for Autism Social Core Symptoms

2020 ◽  
Author(s):  
Yasuhiko Kato ◽  
Hitoshi Kuwabara ◽  
Takashi Okada ◽  
Toshio Munesue ◽  
Seico Benner ◽  
...  
Keyword(s):  
Effect Size ◽  
Neural Plasticity ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Medium Effect ◽  
Double Blind ◽  
Parallel Group ◽  
Core Symptoms

Abstract Background: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6 week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N=106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial.Results: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (False discovery rate (FDR) corrected P=0.043, d=0.74, N=83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR=0.004, d=1.13, N=60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR=0.006, r=-0.485, N=43) and deteriorations between 2 and 4 weeks (PFDR=0.032, r=0.415, N=37).Limitations: The metabolites changes caused by oxytocin administration were quantified using peripheral blood, and therefore may not directly reflect central nervous system changes. Conclusion: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-Methyl-D-Aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy.Trial registration: A multicenter, parallel group, placebo-controlled, double blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders. (The date registered: 30th Oct 2020; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264)

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