Type 1 Diabetes in Pregnancy Doubles Risk for Autism in Offspring

Becky McCall

June 25, 2018

ORLANDO — Risk of autism spectrum disorder (ASD) is increased in the children of mothers with type 1 diabetes new data show, suggesting that the severity of maternal diabetes and timing of exposure may be important in the association.

Specifically, with type 1 diabetes in pregnancy, ASD risk in offspring was found to increase, with a hazard ratio of 2.33 (P = .005), compared with pregnancies not complicated by diabetes.  

"What was so surprising to us from our data was just how high the risk of autism was for children born to mothers with type 1 diabetes," remarked Anny Xiang, PhD, from Kaiser Permanente, Pasadena, California, who presented the study here at the American Diabetes Association (ADA) 2018 Scientific Sessions.

Results of the observational study were simultaneously published as a research letter in JAMA.

The findings also confirm and add to existing knowledge of an association between ASD risk and gestational diabetes or type 2 diabetes in pregnancy (with greatest risk if diagnosed by 26 weeks), as previously reported by Xiang and colleagues (JAMA. 2015;313:1425-1434).

Session moderator Peter Damm, MD, DMSc, professor in obstetrics at Rigshospitalet, Copenhagen, Denmark, said he felt it was a strong study, albeit with some limitations, as recognized by the presenter.

"The finding that type 1 diabetes in pregnancy has a higher hazard ratio for autism than type 2 diabetes, and more so again than gestational diabetes, reflects the degree of maternal hyperglycemia and seems reasonable," he said.

"Likewise, the finding that women diagnosed with gestational diabetes early [≤ 26 weeks' gestation] as opposed to late have a higher risk, showing us a dose–response relationship with regards to different types of diabetes and autism risk."

Nevertheless, he stressed that although diabetes in pregnancy appears to up the risk of autism in offspring, this risk is very small to start with.

"For the individual woman there is a very small risk her child will have this. I would never raise this subject with a patient unless my patient asked me."

First to Study Association Between Type 1 Diabetes in Mom and ASD  

"Our overall interest is looking at the potential impact of hyperglycemia in pregnancy on neural behavior disorders," Xiang explained. "Here in this study, we analyzed our data for any relationships between type 1 diabetes and autism because this has not been done before."

The new retrospective cohort analysis included singleton children born between 28–44 weeks over a 17-year period to 2012 in Kaiser Permanente Southern California hospitals. Children were tracked through electronic records for a median follow-up time of 6.9 years for a clinical diagnosis of ASD including autistic disorders, Asperger syndrome, and pervasive developmental disorder not otherwise specified.

Type 1 diabetes was identified using an algorithm developed for electronic health records data and confirmed by prescription of insulin during pregnancy.

Results were adjusted for potential confounders including birth year, maternal age at delivery, parity, education, self-reported race/ethnicity, median family household income, and history of comorbidity.

Of 419,425 eligible children, 621 were exposed to maternal type 1 diabetes, 9453 to maternal type 2 diabetes, 11,922 to gestational diabetes diagnosed by 26 weeks of gestation, and 24,505 to gestational diabetes diagnosed after 26 weeks of gestation.

Overall, 5827 children were diagnosed with ASD.

Adjusted Risk of ASD in Offspring Associated With In Utero Exposure to Maternal Pre-existing Diabetes During the Index Pregnancy

Type of Maternal Diabetes ASD Incidence Rate per 1000 Children Adjusted Hazard Ratio* P value
None 1.8 1.0 (reference) N/A
Type 1 diabetes 4.4 2.33 .005
Type 2 diabetes 2.36 1.39 <.001
Gestational diagnosed by 26 weeks 2.9 1.26 <.001
Gestational diagnosed after 26 weeks 2.1 0.98 .72
*Birth year, maternal age at delivery, parity, education, self-reported race/ethnicity, median family household income, and history of comorbidity, smoking during pregnancy and pre-pregnancy BMI.

 

All mothers with type 1 and type 2 diabetes, but only 29% of those with gestational diabetes, were dispensed antidiabetic medications during pregnancy.

Potential risk associated with antidiabetic medication exposure was assessed in the gestational diabetes group, adjusting for potential confounders plus gestational age at gestational diabetes diagnosis. Risks were not significantly different between those with versus without antidiabetic medication exposure during pregnancy in the gestational diabetes group (adjusted HR, 1.18; P = .10).

Xiang pointed out that confounding because of paternal risk factors and other intrauterine and post-natal exposures need to be assessed to provide a more complete understanding. Also, the potential role of maternal glycemia, other features of type 1 diabetes, premature birth, and neonatal hypoglycemia remain to be explored.

In conclusion, Xiang and colleagues say, "These results add new information on type 1 diabetes and extend previous findings for pre-existing type 2 diabetes and gestational diabetes." However, " gestational diabetes diagnosed after 26 weeks' gestation was not associated with excess risk compared with no diabetes."

Clinical Implications of Findings

Xiang explained that pregnancy is a screening opportunity for women with an existing underlying defect.

"Often pregnant mothers are young and would never consider going for diabetes screening but they may have an underlying glucose intolerance already that could lead to gestational diabetes and possibly future diabetes," she said.

Reflecting on the clinical implications of the findings, she observed, "No matter whether the woman has type 2, type 1, or gestational diabetes, the women should really be treated with medications during pregnancy."

"In gestational diabetes, most receive lifestyle information as management, but medication only starts if glucose levels hit a certain threshold. So far we don't have data from continuous glucose monitoring to know at this point whether the association is due to suboptimal glucose control during pregnancy."

"It is important for both patient and clinician to monitor glucose control as carefully as possible and make sure it is normal right from the time of conception."

Echoing this, Damm pointed out that ideally glucose monitoring during pregnancy would be more stringent, but cautioned "the finding of increased autism risk with diabetes is not only associated with glucose control but possibly other factors too, for example, preterm birth and socioeconomic status."

"As a clinician, right now I don't think we will change practice because we already try to control metabolism as well as possible in women with diabetes in pregnancy or gestational diabetes," he concluded. 

The authors have reported no relevant financial relationships.

American Diabetes Association 2018 Scientific Sessions. June 22, 2018; Orlando, Florida. Abstract 117-OR.

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