Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies

  1. Chris R Cardwell (c.cardwell{at},
  2. Lars C Stene2,3,
  3. Geir Joner4,
  4. Max K Bulsara5,
  5. Ondrej Cinek6,
  6. Joachim Rosenbauer7,
  7. Johnny Ludvigsson8,
  8. Mireia Jané9,
  9. Jannet Svensson10,
  10. Michael J Goldacre11,
  11. Thomas Waldhoer12,
  12. Przemysława Jarosz-Chobot13,
  13. Suely GA Gimeno14,
  14. Lee-Ming Chuang15,
  15. Roger C Parslow16,
  16. Emma JK Wadsworth17,
  17. Amanda Chetwynd18,
  18. Paolo Pozzilli19,
  19. Girts Brigis20,
  20. Brone Urbonaitė21,
  21. Sandra Šipetić22,
  22. Edith Schober23,
  23. Gabriele Devoti24,
  24. Constantin Ionescu-Tirgoviste25,
  25. Carine E de Beaufort26,
  26. Denka Stoyanov27,
  27. Karsten Buschard28 and
  28. Chris C Patterson1
  1. 1 Centre for Public Health, Queen's University Belfast, UK
  2. 2 Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway
  3. 3 Oslo Research Centre, Oslo University Hospital, Oslo, Norway
  4. 4 Institute of Health Management and Health Economics, University of Oslo, Norway
  5. 5 Institute of Health and Rehabilitation Research, University of Notre Dame, Freemantle, Australia
  6. 6 The 2nd Medical School, Charles University, Prague, Czech Republic
  7. 7 Institute of Biometrics and Epidemiology, German Diabetes Centre, Leibniz Institute at Dusseldorf University, Dusseldorf, Germany
  8. 8 Department of Paediatrics and Diabetes Research Centre, Linkoping University, Linkoping, Sweden
  9. 9 Public Health Division, Department of Health, Barcelona, Spain
  10. 10 Pediatric Department, Glostrup University Hospital, Glostrup Denmark.
  11. 11 Oxford University, Department of Public Health, Oxford, UK.
  12. 12 Department of Epidemiology, Medical University of Vienna, Vienna, Austria.
  13. 13 Department of Pediatric Endocrinology and Diabetes, Medical University of Silesia, Katowice, Poland.
  14. 14 Preventive Medicine Department, Federal University of Sao Paulo, Sao Paulo, Brazil.
  15. 15 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  16. 16 Paediatric Epidemiology Group, University of Leeds, Leeds, UK.
  17. 17 Centre for Occupational and Health Psychology, Cardiff University, Cardiff, UK.
  18. 18 Mathematics & Statistics Department, Lancaster University, Lancaster.
  19. 19 University Campus Bio-Medico, Rome, Italy.
  20. 20 Department of Public Health and Epidemiology, Riga Stradins University, Riga, Latvia.
  21. 21 Institute of Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
  22. 22 Institute of Epidemiology, School of Medicine, Belgrade University, Serbia
  23. 23 Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
  24. 24 Department of Social Sciences and Communication, University of Lecce, Lecce, Italy.
  25. 25 Nutrition and Metabolic Diseases Clinic, “N. Paulescu” Institute of Diabetes, Bucharest, Romania.
  26. 26 Clinique Pédiatrique Luxembourg, Luxembourg.
  27. 27 Children's Diabetic Centre, Sofia, Bulgaria
  28. 28 Bartholin Instituttet, Rigshospitalet, Copenhagen, Denmark.


    Objective To investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognised confounders.

    Research design and methods Relevant studies published before June 2009 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios, and investigate heterogeneity between studies.

    Results Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2%, 9%) increase in childhood type 1 diabetes odds per 5 year increase in maternal age (P=0.006), but there was heterogeneity between studies (heterogeneity I2= 70%). In studies with a low risk of bias there was a more marked increase in diabetes odds of 10% per 5 year increase in maternal age. Adjustments for potential confounders little altered these estimates.

    Conclusions There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.


      • Received August 6, 2009.
      • Accepted October 23, 2009.