Neurodevelopment of Two-Year-Old Children Exposed to Metformin and Insulin in Gestational Diabetes Mellitus

Tertti, Kristiina; Eskola, Eeva; Rönnemaa, Tapani; Haataja, Leena

doi:10.1097/dbp.0000000000000230

Cited by 38 publications

(32 citation statements)

References 18 publications

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“…In another follow-up study of infants exposed to metformin during pregnancies with gestational diabetes, children exposed to metformin weighed more at the age of 12 months, and were heavier and taller at 18 months, however, body composition was similar (368) as was motor, social and linguistic development. Studies looking at neurodevelopment showed similar outcomes between exposed and nonexposed infants at 2 years of age (369,370).…”

Section: Other Antihyperglycemic Agentsmentioning

confidence: 84%

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Diabetes and Pregnancy

Feig¹,

Berger²,

Donovan³

et al. 2018

Canadian Journal of Diabetes

249

169

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All women with pre-existing type 1 or type 2 diabetes should receive preconception care to optimize glycemic control, assess for complications, review medications and begin folic acid supplementation.• All pregnant women without known pre-existing diabetes should be screened for gestational diabetes between 24 to 28 weeks of pregnancy • If you were diagnosed with gestational diabetes during your pregnancy, it is important to:• Breastfeed immediately after birth and for a minimum of 4 months in order to prevent hypoglycemia in your newborn, obesity in childhood, and diabetes for both you and your childConflict of interest statements can be found on page S274.Can J Diabetes 42 (2018) S255-S282

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Section: Other Antihyperglycemic Agentsmentioning

confidence: 84%

“…In summary, long-term follow up from 18 months to 2 years indicate that metformin exposure in-utero does not seem to be harmful with regards to early motor, linguistic, social, (368), metabolic (367,368) and neurodevelopmental (369,370) outcomes. Longerterm follow up is not yet available.…”

Section: Other Antihyperglycemic Agentsmentioning

confidence: 87%

Diabetes and Pregnancy

Feig¹,

Berger²,

Donovan³

et al. 2018

Canadian Journal of Diabetes

249

169

View full text Add to dashboard Cite

show abstract

“…It is important to note that maternal metformin treatment in humans does not compromise neurodevelopmental outcomes when measured in two year old children [60, 61]. Our results show that metformin promotes preservation of fetal DHA (despite reduced maternal liver DHA) important for fetal/neonatal brain development.…”

Section: Discussionmentioning

confidence: 72%

The effects of prenatal metformin on obesogenic diet-induced alterations in maternal and fetal fatty acid metabolism

et al. 2016

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BackgroundMaternal obesity may program the fetus and increase the susceptibility of the offspring to adult diseases. Metformin crosses the placenta and has been associated with decreased inflammation and reversal of fatty liver in obese leptin-deficient mice. We investigated the effects of metformin on maternal and fetal lipid metabolism and hepatic inflammation using a rat model of diet-induced obesity during pregnancy.MethodsFemale Wistar rats (6–7 weeks old) were fed normal or high calorie diets for 5 weeks. After mating with normal-diet fed males, half of the high calorie-fed dams received metformin (300 mg/kg, daily); dams (8 per group) continued diets through gestational day 19. Maternal and fetal livers and fetal brains were analyzed for fatty acids and for fatty acid metabolism-related gene expression. Data were analyzed by ANOVA followed by Dunnett’s post hoc testing.ResultsWhen compared to control-lean maternal livers, obesogenic-diet-exposed maternal livers showed significantly higher saturated fatty acids (14:0 and 16:0) and monounsaturated fatty acids (16:1n7 and 18:1n9) and lower polyunsaturated (18:2n6 and 20:4n6 [arachidonic acid]) and anti-inflammatory n3 polyunsaturated fatty acids (18:3n3 and 22:6n3 [docosahexaenoic acid]) (p < 0.05). Metformin did not affect diet-induced changes in maternal livers. Fetal livers exposed to the high calorie diet showed significantly increased saturated fatty acids (18:0) and monounsaturated fatty acids (18:1n9 and 18:1n7) and decreased polyunsaturated fatty acids (18:2n6, 20:4n6 and 22:6n3) and anti-inflammatory n3 polyunsaturated fatty acids, along with increased gene expression of fatty acid metabolism markers (Fasn, D5d, D6d, Scd1, Lxrα). Metformin significantly attenuated diet-induced inflammation and 18:1n9 and 22:6n3 in fetal livers, as well as n3 fatty acids (p < 0.05). Prenatal obesogenic diet exposure significantly increased fetal liver IFNγ levels (p < 0.05), which was reversed by maternal metformin treatment (p < 0.05).ConclusionsConsumption of a high calorie diet significantly affected maternal and fetal fatty acid metabolism. It reduced anti-inflammatory polyunsaturated fatty acids in maternal and fetal livers, altered gene expression of fatty acid metabolism markers, and induced inflammation in the fetal livers. Prenatal metformin attenuated some diet-induced fatty acid changes and inflammation in the fetal livers without affecting maternal livers, suggesting that maternal metformin may impact fetal/neonatal fatty acid/lipid metabolism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0115-9) contains supplementary material, which is available to authorized users.

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“…The strongest predictors of birth weight >90 percentile, were maternal triglycerides and measures of blood glucose control at gestational week 36 37 . In a follow-up study, no adverse effects on neurological development was detected in Finnish children born to mothers that had received metformin in pregnancy, and who were followed-up until the age of 18 months 38 .…”

Section: Studies Of Metformin Therapy In Gdmmentioning

confidence: 99%

The diversity of gestational diabetes: a therapeutic challenge

Qvigstad

2018

European Journal of Endocrinology

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Metformin as the first drug of choice for glucose lowering in gestational diabetes (GDM) is still controversial, despite recent publications reporting similar outcomes in comparison to insulin, both for offspring and mothers. The use of metformin during pregnancy is increasing and several recent guidelines recommend metformin use in GDM pregnancies. Background, current metformin use and unresolved concerns are discussed in the context of the article from Gante and coworkers.

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Neurodevelopment of Two-Year-Old Children Exposed to Metformin and Insulin in Gestational Diabetes Mellitus

Cited by 38 publications

References 18 publications

Diabetes and Pregnancy

Diabetes and Pregnancy

The effects of prenatal metformin on obesogenic diet-induced alterations in maternal and fetal fatty acid metabolism

The diversity of gestational diabetes: a therapeutic challenge

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