JAMA. online June 23, 2018. doi:10.1001/jama.2018.7614
Anny H. Xiang anny.h.xiang at kp.org , PhD1; Xinhui Wang, PhD1; Mayra P. Martinez, MPH1; et al Kathleen Page, MD2; Thomas A. Buchanan, MD2; R. Klara Feldman, MD3
Maternal preexisting type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) diagnosed by 26 weeks’ gestation have been associated with increased risk of autism spectrum disorder (ASD) in offspring.1 However, little is known about ASD risk associated with maternal preexisting type 1 diabetes (T1D). We extend previous observations by examining the risk of ASD in offspring associated with maternal T1D, T2D, and GDM.
Based on 5800 Autistic children (Kaiser Permanente Hospitals)
|Diabetes while pregnant||Autism Risk Increase|
|Gestational before 26 weeks||1.3|
Items in both categories Autism and Pregnancy are listed here:
- Autism risk reduced 2X by prenatal vitamins (Vitamin D or Folic) – Feb 2019
- Autism associated with low Zinc during pregnancy (Zinc is needed by Vitamin D Receptor) – July 2018
- Maternal Diabetes and Risk of Autism in Offspring – JAMA June 2018
- Hypothesis: male autism risk increased if placental virus and low vitamin D – Feb 2018
- Women who had supplemented with any vitamins were 6 X less likely to have autistic offspring – Jan 2018
- A good Vitamin D Receptor (or perhaps more vitamin D) protects against lead during pregnancy
- Autism rate cut in half when multivitamins (including vitamin D) used during pregnancy – Oct 2017
- ADHD 2 X more likely if Tylenol used a lot during pregnancy (Autism increased too) – Dec 2016
- Autistic child 2.4 X more likely if less than 10 ng of vitamin D during 2nd trimester – April 2017
- Autism risk increased by 44% if there were pregnancy and labor complications (probably low vitamin D) – Kaiser Jan 2017
- Herpes virus infection while pregnant increases Autism risk by 2 X (Vitamin D not mentioned) – Feb 2017
- Autism associated with low vitamin D during pregnancy – Nov 2016
- Autism 2.1 times more likely if obese and PCOS (relationships to vitamin D not mentioned) Oct 2016
- Autism 17 times more likely with excessive Folic Acid and B-12 (now added to bread) – May 2016
- Autism with intellectual disability 2.5 times more likely if low vitamin D during pregnancy – April 2016
- Autism risk increased if short time between pregnancies (no surprise) – April 2016
- Autism rate in siblings reduced 4X by vitamin D: 5,000 IU during pregnancy, 1,000 IU to infants – Feb 2016
- All pregnant women (in UK) should have free vitamin D – Gillie Aug 2015
- Autistic measure 5X more likely if low vitamin D in second trimester – Oct 2012
- Low vitamin D in pregnancy and 2X worse language skills later – Feb 2012
- Autism has different causes but same inflammation in brain in half of autistics – May 2011
- Hypothesis being tested: 5000 IU prevent second autistic child - May 2010
- Vitamin D Newsletter May 2010
- Autism and Vitamin D - Newsletter April 2010
- Overview Autism and vitamin D
- Autism treated by Vitamin D (80 – 120 ng) – Cannell update May 2018
- Autism treated by Vitamin B12 - several studies
- Autism treated by Vitamin D (monthly injection of 150,000 IU) – June 2017
- Autism and Vitamin D – 3 biomarkers found so far – March 2018
- Autism risk factors – many are associated with low vitamin D – meta-meta-analysis March 2017
Pregnancy and Vitamin D
- Healthy pregnancies need lots of vitamin D has the following summary
Reduces Evidence 0. Chance of not conceiving 3.4 times Observe 1. Miscarriage 2.5 times Observe 2. Pre-eclampsia 3.6 times Randomized Controlled Trial 3. Gestational Diabetes 3 times Randomized Controlled Trial 4. Good 2nd trimester sleep quality 3.5 times Observe 5. Premature birth 2 times Randomized Controlled Trial 6. C-section - unplanned 1.6 times Observe Stillbirth - OMEGA-3 4 times RCT - Omega-3 7. Depression AFTER pregnancy 1.4 times Randomized Controlled Trial 8. Small for Gestational Age 1.6 times meta-analysis 9. Infant height, weight, head size
within normal limits
Randomized Controlled Trial 10. Childhood Wheezing 1.3 times Randomized Controlled Trial 11. Additional child is Autistic 4 times Intervention 12.Young adult Multiple Sclerosis 1.9 times Observe 13. Preeclampsia in young adult 3.5 times Randomized Controlled Trial 14. Good motor skills @ age 3 1.4 times Observe 15. Childhood Mite allergy 5 times Randomized Controlled Trial 16. Childhood Respiratory Tract visits 2.5 times Randomized Controlled Trial
Vitamin D both prevents and treats
20+ other diseases
This retrospective cohort study included singleton children born at 28 to 44 weeks’ gestation in Kaiser Permanente Southern California (KPSC) hospitals from January 1, 1995, through December 31, 2012. Children were tracked through electronic health records from age 1 year until the first date of the following: clinical diagnosis of ASD, last date of continuous KPSC membership, death, or study end date (December 31, 2017). The KPSC institutional review board approved this study and provided waiver of participant consent.
Methods to identify ASD, T2D, and GDM exposure were described previously.1 GDM exposure was divided into diagnosis by or after 26 weeks’ gestation based on a prior finding that risk of ASD was elevated for exposure to GDM by 26 weeks.1 T1D was identified using the algorithm developed for electronic health records data 2 and confirmed by prescription of insulin during pregnancy. Potential confounders were birth year, maternal age at delivery, parity, education, self-reported race/ethnicity, median family household income based on residence census tract, history of comorbidity (≥1 diagnosis of heart, lung, kidney, or liver disease; cancer), and child’s sex. Data on maternal smoking and obesity (measured by prepregnancy body mass index [calculated as weight in kilograms divided by height in meters squared]) were available beginning after 2006 (on 36% of the cohort). The missing indicator method was used to additionally adjust for these covariates. Cox regression was used to estimate hazard ratios (HRs) adjusting for potential confounders. All mothers with T1D and T2D, but only 29% of those with GDM, were dispensed antidiabetic medications during pregnancy. Potential risk associated with antidiabetic medication exposure was assessed in the GDM group, adjusting for potential confounders plus the gestational age at GDM diagnosis. SAS Enterprise Guide (SAS Institute), version 5.1, and R (R Foundation), version 3.4.3 (64 bit), were used for data analysis. A 2-sided P value less than .05 was considered significant.
Of 419 425 children (boys, 51%) meeting study criteria, 621 were exposed to maternal T1D, 9453 to maternal T2D, 11 922 to GDM diagnosed by 26 weeks’ gestation, and 24 505 to GDM diagnosed after 26 weeks’ gestation. During a median follow-up of 6.9 years (interquartile range, 3.4-11.9), 5827 children were diagnosed with ASD. Unadjusted average annual ASD incidence rates per 1000 children were 4.4 for exposure to T1D; 3.6 for T2D; 2.9 for GDM by 26 weeks; 2.1 for GDM after 26 weeks; and 1.8 for no diabetes. The Figure depicts the cumulative incidence rates by maternal diabetes exposure groups. Relative to no diabetes exposure, the adjusted HRs for exposure to maternal diabetes were 2.36 (95% CI, 1.36-4.12) for T1D, 1.45 (95% CI, 1.24-1.70) for T2D, 1.30 (95% CI, 1.12-1.51) for GDM by 26 weeks’ gestation, and 0.99 (95% CI, 0.88-1.12) for GDM after 26 weeks. Additional adjustment for maternal smoking during pregnancy and prepregnancy BMI changed results only slightly (Table). Risks were not statistically significantly different between those with vs without antidiabetic medication exposure during pregnancy within the GDM group (adjusted HR, 1.18 [95% CI, 0.97-1.43]; P = .10).
Among the 3 main types of diabetes complicating pregnancy, the risk of ASD in offspring was elevated in mothers with T1D, T2D, and GDM diagnosed by 26 weeks’ gestation compared with no diabetes. These results add new information on T1D and extend previous findings1 for preexisting T2D and GDM. GDM diagnosed after 26 weeks’ gestation was not associated with excess risk compared with no diabetes.
These results suggest that the severity of maternal diabetes and the timing of exposure (early vs late in pregnancy) may be associated with the risk of ASD in offspring of diabetic mothers. The potential role of maternal glycemia; other features of T1D such as autoimmunity and genetic factors3,4; prematurity; and neonatal hypoglycemia5 remains to be explored. Confounding due to paternal risk factors and other intrauterine and postnatal exposures could not be assessed.