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Published in: Diabetologia 1/2014

Open Access 01-01-2014 | Article

Maternal diabetes in pregnancy and offspring cognitive ability: sibling study with 723,775 men from 579,857 families

Authors: Abigail Fraser, Catarina Almqvist, Henrik Larsson, Niklas Långström, Debbie A. Lawlor

Published in: Diabetologia | Issue 1/2014

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Abstract

Aims/hypothesis

The aim of this study was to investigate the association between maternal diabetes in pregnancy and offspring cognitive ability and also to assess whether the association was due to intrauterine mechanisms or shared familial characteristics.

Methods

We linked national registers and conducted a prospective cohort study of singleton Swedish-born men to explore associations between maternal pregnancy diabetes and educational achievement at age 16 years, the age of completing compulsory education in Sweden (n = 391,545 men from 337,174 families, graduating in 1988–1997 and n = 326,033 men from 282,079 families, graduating in 1998–2009), and intelligence quotient (IQ) at the mandatory conscription examination at 18 years of age (n = 664,871 from 543,203 families).

Results

Among non-siblings, maternal diabetes in pregnancy was associated with lower offspring cognitive ability even after adjustment for maternal age at birth, parity, education, early-pregnancy BMI, offspring birth year, gestational age and birthweight. For example, in non-siblings, the IQ of men whose mothers had diabetes in their pregnancy was on average 1.36 points lower (95% CI −2.12, −0.60) than men whose mothers did not have diabetes. In comparison, we found no such association within sibships (mean difference 1.70; 95% CI −1.80, 5.21).

Conclusions/interpretation

The association between maternal diabetes in pregnancy and offspring cognitive outcomes is likely explained by shared familial characteristics and not by an intrauterine mechanism.
Literature
1.
go back to reference Ornoy A (2005) Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes. Pediatr Endocrinol Rev 3:104–113PubMed Ornoy A (2005) Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes. Pediatr Endocrinol Rev 3:104–113PubMed
2.
go back to reference Silverman BL, Rizzo TA, Cho NH, Metzger BE (1998) Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care 21(suppl 2):B142–B149PubMed Silverman BL, Rizzo TA, Cho NH, Metzger BE (1998) Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care 21(suppl 2):B142–B149PubMed
3.
go back to reference Temple RC, Hardiman M, Pellegrini M, Horrocks L, Martinez-Cengotitabengoa MT (2011) Cognitive function in 6- to 12-year-old offspring of women with type 1 diabetes. Diabet Med 28:845–848PubMedCrossRef Temple RC, Hardiman M, Pellegrini M, Horrocks L, Martinez-Cengotitabengoa MT (2011) Cognitive function in 6- to 12-year-old offspring of women with type 1 diabetes. Diabet Med 28:845–848PubMedCrossRef
4.
go back to reference Ornoy A, Ratzon N, Greenbaum C, Peretz E, Soriano D, Dulitzky M (1998) Neurobehaviour of school age children born to diabetic mothers. Arch Dis Child Fetal Neonatal Ed 79:F94–F99PubMedCrossRef Ornoy A, Ratzon N, Greenbaum C, Peretz E, Soriano D, Dulitzky M (1998) Neurobehaviour of school age children born to diabetic mothers. Arch Dis Child Fetal Neonatal Ed 79:F94–F99PubMedCrossRef
5.
go back to reference Nielsen GL, Dethlefsen C, Sorensen HT, Pedersen JF, Molsted-Pedersen L (2007) Cognitive function and army rejection rate in young adult male offspring of women with diabetes. Diabetes Care 30:2827–2831PubMedCrossRef Nielsen GL, Dethlefsen C, Sorensen HT, Pedersen JF, Molsted-Pedersen L (2007) Cognitive function and army rejection rate in young adult male offspring of women with diabetes. Diabetes Care 30:2827–2831PubMedCrossRef
6.
go back to reference Clausen TD, Mortensen EL, Schmidt L et al (2011) Cognitive function in adult offspring of women with type-1 diabetes. Diabet Med 28:838–844PubMedCrossRef Clausen TD, Mortensen EL, Schmidt L et al (2011) Cognitive function in adult offspring of women with type-1 diabetes. Diabet Med 28:838–844PubMedCrossRef
7.
go back to reference Dahlquist G, Kallen B (2007) School marks for Swedish children whose mothers had diabetes during pregnancy: a population-based study. Diabetologia 50:1826–1831PubMedCrossRef Dahlquist G, Kallen B (2007) School marks for Swedish children whose mothers had diabetes during pregnancy: a population-based study. Diabetologia 50:1826–1831PubMedCrossRef
8.
go back to reference Fraser A, Nelson SM, Macdonald-Wallis C, Lawlor DA (2012) Associations of existing diabetes, gestational diabetes, and glycosuria with offspring IQ and educational attainment: the Avon Longitudinal Study of Parents and Children. Exp Diabetes Res 963735 Fraser A, Nelson SM, Macdonald-Wallis C, Lawlor DA (2012) Associations of existing diabetes, gestational diabetes, and glycosuria with offspring IQ and educational attainment: the Avon Longitudinal Study of Parents and Children. Exp Diabetes Res 963735
9.
go back to reference Hunt KJ, Schuller KL (2007) The increasing prevalence of diabetes in pregnancy. Obstet Gynecol Clin N Am 34:173–199CrossRef Hunt KJ, Schuller KL (2007) The increasing prevalence of diabetes in pregnancy. Obstet Gynecol Clin N Am 34:173–199CrossRef
10.
go back to reference Veena SR, Krishnaveni GV, Srinivasan K et al (2010) Childhood cognitive ability: relationship to gestational diabetes mellitus in India. Diabetologia 53:2134–2138PubMedCrossRef Veena SR, Krishnaveni GV, Srinivasan K et al (2010) Childhood cognitive ability: relationship to gestational diabetes mellitus in India. Diabetologia 53:2134–2138PubMedCrossRef
11.
go back to reference Nelson CA, Wewerka S, Thomas KM, Tribby-Walbridge S, deRegnier R, Georgieff M (2000) Neurocognitive sequelae of infants of diabetic mothers. Behav Neurosci 114:950–956PubMedCrossRef Nelson CA, Wewerka S, Thomas KM, Tribby-Walbridge S, deRegnier R, Georgieff M (2000) Neurocognitive sequelae of infants of diabetic mothers. Behav Neurosci 114:950–956PubMedCrossRef
12.
go back to reference Rizzo TA, Dooley SL, Metzger BE, Cho NH, Ogata ES, Silverman BL (1995) Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers. Am J Obstet Gynecol 173:1753–1758PubMedCrossRef Rizzo TA, Dooley SL, Metzger BE, Cho NH, Ogata ES, Silverman BL (1995) Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers. Am J Obstet Gynecol 173:1753–1758PubMedCrossRef
13.
go back to reference Gin H, Vambergue A, Vasseur C et al (2006) Blood ketone monitoring: a comparison between gestational diabetes and non-diabetic pregnant women. Diabetes Metab 32:592–597PubMedCrossRef Gin H, Vambergue A, Vasseur C et al (2006) Blood ketone monitoring: a comparison between gestational diabetes and non-diabetic pregnant women. Diabetes Metab 32:592–597PubMedCrossRef
14.
go back to reference Torloni MR, Betran AP, Horta BL et al (2009) Prepregnancy BMI and the risk of gestational diabetes: a systematic review of the literature with meta-analysis. Obes Rev 10:194–203PubMedCrossRef Torloni MR, Betran AP, Horta BL et al (2009) Prepregnancy BMI and the risk of gestational diabetes: a systematic review of the literature with meta-analysis. Obes Rev 10:194–203PubMedCrossRef
15.
go back to reference Rutter M (2007) Proceeding from observed correlation to causal inference: the use of natural experiments. Perspect Psychol Sci 2:377–395CrossRef Rutter M (2007) Proceeding from observed correlation to causal inference: the use of natural experiments. Perspect Psychol Sci 2:377–395CrossRef
16.
go back to reference Carlstedt B (2000) Cognitive abilities—aspects of structure, process and measurement. PhD thesis, University of Gothenburg, Gothenburg, Sweden Carlstedt B (2000) Cognitive abilities—aspects of structure, process and measurement. PhD thesis, University of Gothenburg, Gothenburg, Sweden
17.
go back to reference Cnattingius S, Ericson A, Gunnarskog J, Kallen B (1990) A quality study of a medical birth registry. Scand J Soc Med 18:143–148PubMed Cnattingius S, Ericson A, Gunnarskog J, Kallen B (1990) A quality study of a medical birth registry. Scand J Soc Med 18:143–148PubMed
18.
go back to reference National Centre for Epidemiology (2003) The Swedish Medical Birth Register: a summary of content and quality. National Centre for Epidemiology, Stockholm National Centre for Epidemiology (2003) The Swedish Medical Birth Register: a summary of content and quality. National Centre for Epidemiology, Stockholm
19.
go back to reference Wennerstad KM, Silventoinen K, Tynelius P, Bergman L, Kaprio J, Rasmussen F (2010) Associations between IQ and cigarette smoking among Swedish male twins. Soc Sci Med 70:575–581PubMedCrossRef Wennerstad KM, Silventoinen K, Tynelius P, Bergman L, Kaprio J, Rasmussen F (2010) Associations between IQ and cigarette smoking among Swedish male twins. Soc Sci Med 70:575–581PubMedCrossRef
20.
go back to reference David AS, Malmberg A, Brandt L, Allebeck P, Lewis G (1997) IQ and risk for schizophrenia: a population-based cohort study. Psychol Med 27:1311–1323PubMedCrossRef David AS, Malmberg A, Brandt L, Allebeck P, Lewis G (1997) IQ and risk for schizophrenia: a population-based cohort study. Psychol Med 27:1311–1323PubMedCrossRef
21.
go back to reference Mann V, de Stavola BL, Leon DA (2004) Separating within and between effects in family studies: an application to the study of blood pressure in children. Stat Med 23:2745–2756PubMedCrossRef Mann V, de Stavola BL, Leon DA (2004) Separating within and between effects in family studies: an application to the study of blood pressure in children. Stat Med 23:2745–2756PubMedCrossRef
22.
go back to reference Lawlor DA, Lichtenstein P, Långström N (2011) Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families. Circulation 123:258–265PubMedCrossRef Lawlor DA, Lichtenstein P, Långström N (2011) Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families. Circulation 123:258–265PubMedCrossRef
23.
go back to reference Van Lieshout RJ, Taylor VH, Boyle MH (2011) Pre-pregnancy and pregnancy obesity and neurodevelopmental outcomes in offspring: a systematic review. Obes Rev 12:e548–e559PubMedCrossRef Van Lieshout RJ, Taylor VH, Boyle MH (2011) Pre-pregnancy and pregnancy obesity and neurodevelopmental outcomes in offspring: a systematic review. Obes Rev 12:e548–e559PubMedCrossRef
25.
go back to reference Eriksen W, Sundet JM, Tambs K (2010) Birth weight standardized to gestational age and intelligence in young adulthood: a register-based birth cohort study of male siblings. Am J Epidemiol 172:530–536PubMedCrossRef Eriksen W, Sundet JM, Tambs K (2010) Birth weight standardized to gestational age and intelligence in young adulthood: a register-based birth cohort study of male siblings. Am J Epidemiol 172:530–536PubMedCrossRef
26.
go back to reference Bonilla C, Lawlor D, Ben-Shlomo Y et al (2012) Maternal and offspring fasting glucose and type 2 diabetes-associated genetic variants and cognitive function at age 8: a Mendelian randomization study in the Avon longitudinal study of parents and children. BMC Med Genet 13:90PubMedCrossRef Bonilla C, Lawlor D, Ben-Shlomo Y et al (2012) Maternal and offspring fasting glucose and type 2 diabetes-associated genetic variants and cognitive function at age 8: a Mendelian randomization study in the Avon longitudinal study of parents and children. BMC Med Genet 13:90PubMedCrossRef
27.
go back to reference Agardh E, Allebeck P, Hallqvist J, Moradi T, Sidorchuk A (2011) Type 2 diabetes incidence and socio-economic position: a systematic review and meta-analysis. Int J Epidemiol 40:804–818PubMedCrossRef Agardh E, Allebeck P, Hallqvist J, Moradi T, Sidorchuk A (2011) Type 2 diabetes incidence and socio-economic position: a systematic review and meta-analysis. Int J Epidemiol 40:804–818PubMedCrossRef
28.
go back to reference Joseph KS, Liston RM, Dodds L, Dahlgren L, Allen AC (2007) Socioeconomic status and perinatal outcomes in a setting with universal access to essential health care services. CMAJ 177:583–590PubMedCrossRef Joseph KS, Liston RM, Dodds L, Dahlgren L, Allen AC (2007) Socioeconomic status and perinatal outcomes in a setting with universal access to essential health care services. CMAJ 177:583–590PubMedCrossRef
29.
go back to reference Frisell T, Oberg S, Kuja-Halkola R, Sjolander A (2012) Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology 23:713–720PubMedCrossRef Frisell T, Oberg S, Kuja-Halkola R, Sjolander A (2012) Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology 23:713–720PubMedCrossRef
30.
go back to reference National Institute for Health and Clinical Excellence (2008) Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. NICE Clinical Guideline 6. NICE, London National Institute for Health and Clinical Excellence (2008) Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. NICE Clinical Guideline 6. NICE, London
31.
go back to reference Patel S, Fraser A, Davey SG et al (2012) Associations of gestational diabetes, existing diabetes, and glycosuria with offspring obesity and cardiometabolic outcomes. Diabetes Care 35:63–71PubMedCrossRef Patel S, Fraser A, Davey SG et al (2012) Associations of gestational diabetes, existing diabetes, and glycosuria with offspring obesity and cardiometabolic outcomes. Diabetes Care 35:63–71PubMedCrossRef
32.
go back to reference Silverman BL, Metzger BE, Cho NH, Loeb CA (1995) Impaired glucose tolerance in adolescent offspring of diabetic mothers. Relationship to fetal hyperinsulinism. Diabetes Care 18:611–617PubMedCrossRef Silverman BL, Metzger BE, Cho NH, Loeb CA (1995) Impaired glucose tolerance in adolescent offspring of diabetic mothers. Relationship to fetal hyperinsulinism. Diabetes Care 18:611–617PubMedCrossRef
Metadata
Title
Maternal diabetes in pregnancy and offspring cognitive ability: sibling study with 723,775 men from 579,857 families
Authors
Abigail Fraser
Catarina Almqvist
Henrik Larsson
Niklas Långström
Debbie A. Lawlor
Publication date
01-01-2014
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 1/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-3065-z

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