Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis

Ahmed Elhakeem; Amy E Taylor; Hazel M Inskip; Jonathan Y Huang; Toby Mansell; Carina Rodrigues; Federica Asta; Sophia M Blaauwendraad; Siri E Håberg; Jane Halliday; Margreet W Harskamp-van Ginkel; Jian-Rong He; Vincent W V Jaddoe; Sharon Lewis; Gillian M Maher; Yannis Manios; Fergus P McCarthy; Irwin K M Reiss; Franca Rusconi; Theodosia Salika; Muriel Tafflet; Xiu Qiu; Bjørn O Åsvold; David Burgner; Jerry K Y Chan; Luigi Gagliardi; Romy Gaillard; Barbara Heude; Maria C Magnus; George Moschonis; Deirdre Murray; Scott M Nelson; Daniela Porta; Richard Saffery; Henrique Barros; Johan G Eriksson; Tanja G M Vrijkotte; Deborah A Lawlor

doi:10.1093/eurheartj/ehac726

Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis

Eur Heart J. 2023 Apr 21;44(16):1464-1473. doi: 10.1093/eurheartj/ehac726.

Authors

Ahmed Elhakeem^{1

2}, Amy E Taylor^{1

2

3}, Hazel M Inskip⁴, Jonathan Y Huang^{5

6}, Toby Mansell^{7

8}, Carina Rodrigues^{9

10}, Federica Asta¹¹, Sophia M Blaauwendraad^{12

13}, Siri E Håberg¹⁴, Jane Halliday^{7

8}, Margreet W Harskamp-van Ginkel¹⁵, Jian-Rong He¹⁶, Vincent W V Jaddoe^{13

12}, Sharon Lewis^{7

8}, Gillian M Maher^{17

18}, Yannis Manios^{19

20}, Fergus P McCarthy^{18

21}, Irwin K M Reiss¹³, Franca Rusconi²², Theodosia Salika⁴, Muriel Tafflet²³, Xiu Qiu¹⁶, Bjørn O Åsvold^{24

25

26}, David Burgner^{7

27

28}, Jerry K Y Chan^{29

30}, Luigi Gagliardi²², Romy Gaillard^{12

13}, Barbara Heude²³, Maria C Magnus¹⁴, George Moschonis³¹, Deirdre Murray^{18

32}, Scott M Nelson^{3

33}, Daniela Porta¹¹, Richard Saffery^{7

8}, Henrique Barros^{9

10}, Johan G Eriksson^{5

34

35

36}, Tanja G M Vrijkotte¹⁵, Deborah A Lawlor^{1

2

3}

Affiliations

¹ MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
² Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
³ NIHR Bristol Biomedical Research Centre, Bristol, UK.
⁴ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
⁵ Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, Singapore, Singapore.
⁶ Duke-NUS Medical School, Centre for Quantitative Medicine, Singapore, Singapore.
⁷ Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia.
⁸ University of Melbourne, Parkville, VIC, Australia.
⁹ EPIUnit-Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.
¹⁰ Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Porto, Portugal.
¹¹ Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
¹² The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
¹³ Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
¹⁴ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
¹⁵ Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
¹⁶ Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
¹⁷ School of Public Health, University College Cork, Cork, Ireland.
¹⁸ The Irish Centre for Maternal and Child Health Research (INFANT), University College Cork, Cork, Ireland.
¹⁹ Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
²⁰ Institute of Agri-Food and Life Sciences, Hellenic Mediterranean University Research Centre, Heraklion, Greece.
²¹ Department of Obstetrics and Gynaecology, University College Cork, Cork, Ireland.
²² Department of Mother and Child Health, Ospedale Versilia, Viareggio, AUSL Toscana Nord Ovest, Pisa, Italy.
²³ Université Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS), Paris, France.
²⁴ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
²⁵ HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
²⁶ Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
²⁷ Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
²⁸ Department of Paediatrics, Monash University, Clayton, VIC, Australia.
²⁹ Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore.
³⁰ Academic Clinical Program in Obstetrics and Gynaecology, Duke-NUS Medical School, Singapore, Singapore.
³¹ Department of Food, Nutrition and Dietetics, School of Allied Health, Human Services and Sport, College of Science, Health and Engineering, La Trobe University, Melbourne, Australia.
³² Department of Pediatrics and Child Health, University College Cork, Cork, Ireland.
³³ School of Medicine, University of Glasgow, Glasgow, UK.
³⁴ Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
³⁵ Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³⁶ Folkhälsan Research Center, Helsinki, Finland.

Abstract

Aims: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age.

Methods and results: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant.

Conclusion: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.

Keywords: In vitro fertilization; Blood pressure; Glucose; Lipids; Meta-analysis; Pooled longitudinal trajectory analysis.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Blood Pressure / physiology
Cardiovascular Diseases* / epidemiology
Cardiovascular Diseases* / etiology
Cohort Studies
Humans
Hypertension*
Infant
Reproductive Techniques, Assisted / adverse effects
Triglycerides
Young Adult

Substances

Triglycerides

Abstract

Publication types

MeSH terms

Substances

Grants and funding