Bernadeta Patro Golab1, Susana Santos2, Ellis Voerman2, Debbie A Lawlor3, Vincent W V Jaddoe4, Romy Gaillard5. 1. The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Paediatrics, Medical University of Warsaw, Warsaw, Poland. 2. The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, Netherlands. 3. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK. 4. The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, Netherlands. 5. The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, Netherlands. Electronic address: r.gaillard@erasmusmc.nl.
Abstract
BACKGROUND: Gestational diabetes and gestational hypertensive disorders are associated with offspring obesity, but the role of maternal adiposity in these associations remains unclear. We aimed to investigate whether these pregnancy complications affect the odds of offspring obesity independently of maternal obesity. METHODS: We did an individual participant data (IPD) meta-analysis of mother-offspring pairs from prospective birth cohort studies that had IPD on mothers with singleton liveborn children born from 1989 onwards and had information available about maternal gestational diabetes, gestational hypertension or pre-eclampsia, and childhood body-mass index (BMI). We applied multilevel mixed-effects models to assess associations of gestational diabetes, gestational hypertension, and pre-eclampsia with BMI SD scores and the odds of overweight and obesity throughout childhood, adjusting for lifestyle characteristics (offspring's sex, maternal age, educational level, ethnicity, parity, and smoking during pregnancy). We then explored the extent to which any association was explained by maternal pre-pregnancy or early-pregnancy BMI. FINDINGS: 160 757 mother-offspring pairs from 34 European or North American cohorts were analysed. Compared with uncomplicated pregnancies, gestational diabetes was associated with increased odds of overweight or obesity throughout childhood (odds ratio [OR] 1·59 [95% CI 1·36 to 1·86] for early childhood [age 2·0-4·9 years], 1·41 [1·26 to 1·57] for mid childhood [5·0-9·9 years], and 1·32 [0·97 to 1·78] for late childhood [10·0-17·9 years]); however, these associations attenuated towards the null following adjustment for maternal BMI (OR 1·35 [95% CI 1·15 to 1·58] for early childhood, 1·12 [1·00 to 1·25] for mid childhood, and 0·96 [0·71 to 1·31] for late childhood). Likewise, gestational hypertension was associated with increased odds of overweight throughout childhood (OR 1·19 [95% CI 1·01 to 1·39] for early childhood, 1·23 [1·15 to 1·32] for mid childhood, and 1·49 [1·30 to 1·70] for late childhood), but additional adjustment for maternal BMI largely explained these associations (1·01 [95% CI 0·86 to 1·19] for early childhood, 1·02 [0·95 to 1·10] for mid childhood, and 1·18 [1·03 to 1·36] for late childhood). Pre-eclampsia was associated with decreased BMI in early childhood only (difference in BMI SD score -0·05 SD score [95% CI -0·09 to -0·01]), and this association strengthened following additional adjustment for maternal BMI. INTERPRETATION: Although lowering maternal risk of gestational diabetes, gestational hypertension, and pre-eclampsia is important in relation to maternal and fetal pregnancy outcomes, such interventions are unlikely to have a direct impact on childhood obesity. Preventive strategies for reducing childhood obesity should focus on maternal BMI rather than on pregnancy complications. FUNDING: EU's Horizon 2020 research and innovation programme (LifeCycle Project).
BACKGROUND:Gestational diabetes and gestational hypertensive disorders are associated with offspring obesity, but the role of maternal adiposity in these associations remains unclear. We aimed to investigate whether these pregnancy complications affect the odds of offspring obesity independently of maternal obesity. METHODS: We did an individual participant data (IPD) meta-analysis of mother-offspring pairs from prospective birth cohort studies that had IPD on mothers with singleton liveborn children born from 1989 onwards and had information available about maternal gestational diabetes, gestational hypertension or pre-eclampsia, and childhood body-mass index (BMI). We applied multilevel mixed-effects models to assess associations of gestational diabetes, gestational hypertension, and pre-eclampsia with BMI SD scores and the odds of overweight and obesity throughout childhood, adjusting for lifestyle characteristics (offspring's sex, maternal age, educational level, ethnicity, parity, and smoking during pregnancy). We then explored the extent to which any association was explained by maternal pre-pregnancy or early-pregnancy BMI. FINDINGS: 160 757 mother-offspring pairs from 34 European or North American cohorts were analysed. Compared with uncomplicated pregnancies, gestational diabetes was associated with increased odds of overweight or obesity throughout childhood (odds ratio [OR] 1·59 [95% CI 1·36 to 1·86] for early childhood [age 2·0-4·9 years], 1·41 [1·26 to 1·57] for mid childhood [5·0-9·9 years], and 1·32 [0·97 to 1·78] for late childhood [10·0-17·9 years]); however, these associations attenuated towards the null following adjustment for maternal BMI (OR 1·35 [95% CI 1·15 to 1·58] for early childhood, 1·12 [1·00 to 1·25] for mid childhood, and 0·96 [0·71 to 1·31] for late childhood). Likewise, gestational hypertension was associated with increased odds of overweight throughout childhood (OR 1·19 [95% CI 1·01 to 1·39] for early childhood, 1·23 [1·15 to 1·32] for mid childhood, and 1·49 [1·30 to 1·70] for late childhood), but additional adjustment for maternal BMI largely explained these associations (1·01 [95% CI 0·86 to 1·19] for early childhood, 1·02 [0·95 to 1·10] for mid childhood, and 1·18 [1·03 to 1·36] for late childhood). Pre-eclampsia was associated with decreased BMI in early childhood only (difference in BMI SD score -0·05 SD score [95% CI -0·09 to -0·01]), and this association strengthened following additional adjustment for maternal BMI. INTERPRETATION: Although lowering maternal risk of gestational diabetes, gestational hypertension, and pre-eclampsia is important in relation to maternal and fetal pregnancy outcomes, such interventions are unlikely to have a direct impact on childhood obesity. Preventive strategies for reducing childhood obesity should focus on maternal BMI rather than on pregnancy complications. FUNDING: EU's Horizon 2020 research and innovation programme (LifeCycle Project).
Authors: David J Pettitt; Sonia McKenna; Ciara McLaughlin; Christopher C Patterson; David R Hadden; David R McCance Journal: Diabetes Care Date: 2010-03-09 Impact factor: 17.152
Authors: Mercedes de Onis; Adelheid W Onyango; Elaine Borghi; Amani Siyam; Chizuru Nishida; Jonathan Siekmann Journal: Bull World Health Organ Date: 2007-09 Impact factor: 9.408
Authors: Thomas P A Debray; Karel G M Moons; Ghada Mohammed Abdallah Abo-Zaid; Hendrik Koffijberg; Richard David Riley Journal: PLoS One Date: 2013-04-09 Impact factor: 3.240
Authors: Agnes M M Sonnenschein-van der Voort; Lidia R Arends; Johan C de Jongste; Isabella Annesi-Maesano; S Hasan Arshad; Henrique Barros; Mikel Basterrechea; Hans Bisgaard; Leda Chatzi; Eva Corpeleijn; Sofia Correia; Leone C Craig; Graham Devereux; Cristian Dogaru; Miroslav Dostal; Karel Duchen; Merete Eggesbø; C Kors van der Ent; Maria P Fantini; Francesco Forastiere; Urs Frey; Ulrike Gehring; Davide Gori; Anne C van der Gugten; Wojciech Hanke; A John Henderson; Barbara Heude; Carmen Iñiguez; Hazel M Inskip; Thomas Keil; Cecily C Kelleher; Manolis Kogevinas; Eskil Kreiner-Møller; Claudia E Kuehni; Leanne K Küpers; Kinga Lancz; Pernille S Larsen; Susanne Lau; Johnny Ludvigsson; Monique Mommers; Anne-Marie Nybo Andersen; Lubica Palkovicova; Katharine C Pike; Costanza Pizzi; Kinga Polanska; Daniela Porta; Lorenzo Richiardi; Graham Roberts; Anne Schmidt; Radim J Sram; Jordi Sunyer; Carel Thijs; Maties Torrent; Karien Viljoen; Alet H Wijga; Martine Vrijheid; Vincent W V Jaddoe; Liesbeth Duijts Journal: J Allergy Clin Immunol Date: 2014-02-12 Impact factor: 10.793
Authors: Jami L Josefson; Patrick M Catalano; William L Lowe; Denise M Scholtens; Alan Kuang; Alan R Dyer; Lynn P Lowe; Boyd E Metzger Journal: J Clin Endocrinol Metab Date: 2020-07-01 Impact factor: 5.958
Authors: Katherine A Sauder; Traci A Bekelman; Kylie K Harrall; Deborah H Glueck; Dana Dabelea Journal: Pediatr Obes Date: 2019-07-05 Impact factor: 4.000
Authors: Ellis Voerman; Susana Santos; Hazel Inskip; Pilar Amiano; Henrique Barros; Marie-Aline Charles; Leda Chatzi; George P Chrousos; Eva Corpeleijn; Sarah Crozier; Myriam Doyon; Merete Eggesbø; Maria Pia Fantini; Sara Farchi; Francesco Forastiere; Vagelis Georgiu; Davide Gori; Wojciech Hanke; Irva Hertz-Picciotto; Barbara Heude; Marie-France Hivert; Daniel Hryhorczuk; Carmen Iñiguez; Anne M Karvonen; Leanne K Küpers; Hanna Lagström; Debbie A Lawlor; Irina Lehmann; Per Magnus; Renata Majewska; Johanna Mäkelä; Yannis Manios; Monique Mommers; Camilla S Morgen; George Moschonis; Ellen A Nohr; Anne-Marie Nybo Andersen; Emily Oken; Agnieszka Pac; Eleni Papadopoulou; Juha Pekkanen; Costanza Pizzi; Kinga Polanska; Daniela Porta; Lorenzo Richiardi; Sheryl L Rifas-Shiman; Nel Roeleveld; Luca Ronfani; Ana C Santos; Marie Standl; Hein Stigum; Camilla Stoltenberg; Elisabeth Thiering; Carel Thijs; Maties Torrent; Tomas Trnovec; Marleen M H J van Gelder; Lenie van Rossem; Andrea von Berg; Martine Vrijheid; Alet Wijga; Oleksandr Zvinchuk; Thorkild I A Sørensen; Keith Godfrey; Vincent W V Jaddoe; Romy Gaillard Journal: JAMA Date: 2019-05-07 Impact factor: 56.272
Authors: Angela Pinot de Moira; Sido Haakma; Katrine Strandberg-Larsen; Esther van Enckevort; Marjolein Kooijman; Tim Cadman; Marloes Cardol; Eva Corpeleijn; Sarah Crozier; Liesbeth Duijts; Ahmed Elhakeem; Johan G Eriksson; Janine F Felix; Sílvia Fernández-Barrés; Rachel E Foong; Anne Forhan; Veit Grote; Kathrin Guerlich; Barbara Heude; Rae-Chi Huang; Marjo-Riitta Järvelin; Anne Cathrine Jørgensen; Tuija M Mikkola; Johanna L T Nader; Marie Pedersen; Maja Popovic; Nina Rautio; Lorenzo Richiardi; Justiina Ronkainen; Theano Roumeliotaki; Theodosia Salika; Sylvain Sebert; Johan L Vinther; Ellis Voerman; Martine Vrijheid; John Wright; Tiffany C Yang; Faryal Zariouh; Marie-Aline Charles; Hazel Inskip; Vincent W V Jaddoe; Morris A Swertz; Anne-Marie Nybo Andersen Journal: Eur J Epidemiol Date: 2021-04-21 Impact factor: 12.434