Association of Maternal Diabetes With Autism in Offspring

Jane Oh, Mercer University College of Pharmacy 2015

The National Institute of Neurological Disorders and Stroke (NINDS) describes Autism spectrum disorder (ASD) as a range of complex neurological disorders, characterized by social impairments, communication difficulties, and restricted, repetitive, and stereotyped patterns of behavior. The most severe form of ASD as described by NINDS is known as autistic disorder, autism, or classical ASD.1

The Centers for Disease Control and Prevention (CDC) states that ASD is found among all racial, ethnic, and socioeconomic groups, but is found in boys about five times more than girls. The CDC estimates that about one in 68 children have ASD.2

According to Autism Society, there is no single cause for ASD, but it is generally accepted that it is due to brain abnormalities in structure or function. Theories being researched include links from heredity, genetics, and medical problems. Other research investigations include problems during pregnancy or delivery, and environmental factors.3

Title: Association of Maternal Diabetes With Autism in Offspring4
Design Retrospective longitudinal cohort study; N= 322,323
Objective

(Primary)

To assess autism spectrum disorder (ASD) risk associated with intrauterine exposure to pre-existing type two diabetes and gestational diabetes mellitus (GDM) by gestational age at GDM diagnosis
Study Groups Maternal pre-existing type two diabetes (n= 6,496), GDM diagnosed at 26 weeks gestation or earlier (n= 7,456) or after 26 weeks gestation (n= 17,579), or no diabetes (n= 290,792) during the index pregnancy
Methods Singleton children born in 1995-2009 at Kaiser Permanente Southern California (KPSC) hospitals tracked from birth until the first of the following: date of clinical diagnosis of ASD, last date of KPSC health plan membership, death due to any cause, or December 31, 2012
Duration Births between January 1, 1995 to December 31, 2009
Primary outcome measure Clinical diagnosis of ASD in offspring
Baseline Characteristics Unexposed (n= 290,792): mean age 29.2; parity 0= 115,603, 1= 94,858, >2= 77,002; education high school or lower= 124,832, some college= 79,150, college graduate or higher 80,470; household annual income, $ <30,000= 24,475, 30,000-49,999= 99,360; 50,000-69,999= 90,669; 70,000-89,999= 45,380, >90,000= 28,763; history of comorbidity 19,996; pre-eclampsia/eclampsia 10,282; smoking during pregnancy 556; child characteristics: gestational age at birth, wk= 39.3, female sex= 143,550

Gestational diabetes mellitus (n= 25, 035): mean age 32.4; parity 0= 8,586, 1= 7,503, >2= 8,627; education high school or lower= 10,981, some college= 6,825, college graduate or higher 6,846; household annual income, $ <30,000= 2,013, 30,000-49,999= 8,873; 50,000-69,999= 7,903; 70,000-89,999= 3,752, >90,000= 2,336; history of comorbidity 2,086; preeclampsia/eclampsia 1,269; smoking during pregnancy 63; child characteristics: gestational age at birth, wk= 38.8, female sex= 12,147

Preexisting Type two diabetes (n= 6,496): mean age 32.7; parity 0= 2,108, 1= 2,145, >2= 2,153; education high school or lower= 2,619, some college= 1,986, college graduate or higher 1,781; household annual income, $ <30,000= 615, 30,000-49,999= 2,400; 50,000-69,999= 1,966; 70,000-89,999= 919, >90,000= 564; history of comorbidity 3,188; pre-eclampsia/eclampsia 542; smoking during pregnancy 20; child characteristics: gestational age at birth, wk= 38.5, female sex= 3,204

Results Clinical diagnosis of ASD in offspring: N= 3,388

Exposure to pre-existing type two diabetes, n= 115, p< .001

Exposure to GDM at < 26 weeks, n= 130, p< .001

Exposure to GDM at > 26 to < 30 weeks, n= 101, p= .55

Exposure to GDM at > 30 weeks, n= 79, p= .77

Unexposed, n= 2,963

Adverse Events Common Adverse Effects: Not applicable
Serious Adverse Events: Not applicable
Percentage that Discontinued due to Adverse Events: Not applicable
Study Author Conclusions In this large, multiethnic clinical cohort of singleton children born at 28 to 44 weeks’ gestation, exposure to maternal GDM diagnosed by 26 weeks’ gestation was associated with risk of ASD in offspring.

There was no statistically significant association between maternal pre-existing type two diabetes and the risk of ASD in offspring, but GDM diagnosed by 26 weeks’ gestation had a statistically significant risk of ASD in offspring. The authors speculate that the cause may be due to untreated hyperglycemia during early critical brain developmental windows. In the case of pre-existing type two diabetes, patients may have been treated aggressively during pregnancy, thus reducing this effect on fetal brain development. The results reported are not truly reflective of the actual data among participants. For example, missing data and participants who were no longer in the KPSC health plan by age one were not included in the final analysis; thus, all participants are not accounted for. The results do not give a definitive conclusion as to whether there would be a reduced risk of ASD in offspring through early diagnosis and treatment of GDM. Regardless, it is important to diagnose and treat GDM for the health of the mother, whether there is a correlation of ASD in their children or not.

References:

  1. Autism Fact Sheet. National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/disorders/autism/detail_autism.htm. Accessed April 18, 2015.
  2. Facts about ASD. Centers for Disease Control and Prevention. http://www.cdc.gov/ncbddd/autism/facts.html. Accessed April 18, 2015.
  3. About autism: Causes. Autism Society. http://www.autism-society.org/what-is/causes/. Accessed April 18, 2015.
  4. Xiang AH, Wang X, Martinez MP, et al. Association of maternal diabetes with autism in offspring. JAMA. 2015; 313(14): 1425-34. DOI: 10.1001/jama.2015.2707
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