Induction of labor does not hike the risk for Autism Spectrum disorders.

Clinical Pearls:

• Contrary to the findings of earlier study, Induction of labor does not increase the risk for development of Autism Spectrum disorders(ASD).

Autism Spectrum disorders(ASD) is a group of complex developmental disability that affects a person ability to interact and communicate socially. It includes several conditions that were earlier diagnosed separately and include autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome.

According to CDC about 1% of world population have ASD. It is the fastest growing developmental disability in US and the current prevalence is 1 in 64 births and has increased 119.4 percent from 2000 (1 in 150) to 2010 (1 in 68).[1] An article published in JAMA Pediatric 2014 by Buescher et al. estimated that about 3.5 million people in US live with ASD.[2]

Numerous pregnancy related risk factors have been attributed in putting the children at high risk for ASD like children that were born to older parents,  were preterm or low birth weight, born with other chromosomal disorders like  Down syndrome, fragile X syndrome, tuberous sclerosis and  those delivered by cesarean section.

A study published in Annals of Epidemiology attributed three perinatal risk factors like being born too early, too small, and/or by Cesarean delivery to be responsible for 12-13% of ASD in children.[3]

Many other studies have examined the mother’s use of  serotonin uptake  inhibitors (SSRIs) and increasing use of ART as a causative factor for  sudden increase in prevalence of ASD.

Another large population based study published in JAMA pediatrics in October,2013 concluded that “Compared with children born to mothers who received neither labor induction nor augmentation, children born to mothers who were induced and augmented, induced only, or augmented only experienced increased odds of autism after controlling for potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth year. The observed associations between labor induction/augmentation were particularly pronounced in male children.”[4]

This study sparked a widespread debate between physicians and researchers and the lead author of the study Dr. Gregory proposed the culprit to be oxytocin in induced or augmented labors, putting these children at high risk for ASD. After this controversy ACOG put out a committee opinion (597) in 2014 stating that “Current evidence does not support a conclusion that labor induction or augmentation causes autism spectrum disorder (ASD) in newborns, available evidence is inconsistent and does not demonstrate causation.”[5]

A recent study conducted by researchers at Harvard T.H. Chan School of public health in Boston and published in JAMA pediatrics online first on July 25, 2016 found no association between induction of labor and ASD. This large nationwide study performed in Sweden, followed up a cohort of 1,362,950 children born between 1992-2005. Out of which 1.6% (22077) children were diagnosed with ASD by ages 8 years through 21 years.  

In 11% of the mothers’ labor induction was done due to preeclampsia, gestational diabetes and chronic hypertension. After the statistical analysis, the study found an association between labor induction and ASD but when the analysis was performed between siblings and close relatives the association was not documented.

Siblings share many genetic, socioeconomic and maternal characteristics that may increase the risk for development of ASD, so if association is not documented when comparing with them, the association probably does not exist.

The finding of this large study suggests that if clinically indicated, decision to induce labor should not be withheld in fear of baby developing ASD. Not to induce the labor when indicated may have adverse neonatal consequences.

Dr. Bateman concludes "Overall, these findings should provide reassurance to women who are about to give birth, that having their labor induced will not increase their child's risk of developing autism spectrum disorders."

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[1] https://www.cdc.gov/ncbddd/autism/facts.html

[2] http://www.ncbi.nlm.nih.gov/pubmed/24911948

[3] Schieve LA, Tian LH, Baio J, Rankin K, Rosenberg D, Wiggins L, Maenner MJ, Yeargin-Allsopp M, Durkin M, Rice C, King L, Kirby RS, Wingate MS, Devine O. Annals of Epidemiology. January 2014. [epub ahead of print]

[4] Gregory SG, Anthopolos R, Osgood CE, Grotegut CA, Miranda M. Association of Autism With Induced or Augmented Childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) Databases. JAMA Pediatr.2013;167(10):959-966. doi:10.1001/jamapediatrics.2013.2904.

[5] http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Labor-Induction-or-Augmentation-and-Autism

Excess Folate and Vitamin B12 levels in pregnancy linked to Autism.

 Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social impairment, abnormal communication and repetitive or unusual behavior.

It is one of the rapidly growing developmental disorder in USA, now affecting 1 in 68 children and 1 in 42 boys. Boys are nearly 5 times more likely to develop Autism than girls and there is no medical detection , screening or cure for Autism. 

Some of the known risk factors for Autism spectrum disorder (ASD) are older age of parents, prematurity, LBW, previous sibling being diagnosed with ASD, certain genetic or chromosomal conditions like  Down syndrome, fragile X syndrome,tuberous sclerosis. It also co-occurs with other developmental, psychiatric, neurologic, chromosomal, and genetic diagnoses.

It is well established fact that adequate levels of folic acid are necessary for preventing neural tube defects (NTDs) and pregnant women are advised to start folic acid supplementation as soon as they start planning their pregnancy and through first trimester. In US breads, cereals and other breakfast items are fortified with folic acid.

But, as the saying goes ‘excess of everything is bad’, so is the case with excess of folic acid in blood during the antenatal period. A recent study presented at the 2016 International Meeting for Autism Research in Baltimore have linked excess folic acid and B12 to Autism. The study is also published in April issue of The FASEB Journal.

The researchers analyzed data from nearly 1,391 mother-child pairs in the Boston Birth Cohort, which is an ongoing longitudinal prospective birth cohort study consisting of low-income urban, primarily minority mother-offspring pairs. The children were followed from birth through childhood between 1998–2013. Maternal Blood samples were collected 48-72 hours post delivery and analyzed for plasma folate, Vit B12 and homocysteine  levels. 

A total of 107 infants were diagnosed with autism, Asperger syndrome, and/or pervasive developmental disorder not otherwise specified and were categorized as having ASD.

According to the World Health Organization folate levels between 13.5 and 45.3 nanomoles per liter represent adequate amount of folate for a woman in her first trimester of pregnancy. But, well established threshold for Vit B12 is yet to be researched at.

The researchers found that one in 10 of the study subject had an excess amount of folate (more than 59 nanomoles per liter) and six percent had an excess amount of vitamin B12 (more than 600 picomoles per liter).

It is not known that why some women have such high levels of folate and Vit B12. The researchers link it with diet, genetic makeup for metabolizing folates and supplementation or a combination of all these.  

The findings from this study are still very premature and not been peer-reviewed. The data has to be looked at closely and multiple studies are required before a recommendation can be made.

Principal investigator Daniele Fallin, PhD, director, Wendy Klag Center for Autism and Developmental Disabilities, John Hopkins Bloomberg School of Public Health, said during a press briefing. "When we looked at the vitamin supplementation evidence, we saw what our colleagues see ― that indeed, women who took vitamin supplementation during pregnancy had a lower risk of autism in their children and that is very consistent with the literature." 

"But when we looked at women who had excessively high levels of folate, we saw that very high levels of folate in the mother were responsible for about a twofold increased risk for autism in their child [P = .007], and when we looked at B12, women who had excessively high levels of B12 had a threefold increased risk for their child to have autism [P = .001], while women who had extreme levels of both folate and vitamin B12 had a 17.6 times greater risk of having their child diagnosed with an ASD [autism spectrum disorder] later on [P < .001]," she added.

 "We have long known that a folate deficiency in pregnant mothers is detrimental to her child's development. But what this tells us is that excessive amounts may also cause harm. We must aim for optimal levels of this important nutrient," said Fallin.

This study gives us some important future research topics about how much folic acid supplementation is enough and what constitutes the excess and part played by genetics and diet.

"So for now, the public health message is, supplementation is good, but there may be a subset of women whose levels are extremely high, and these extreme levels may be harmful."

Women should be cautioned about randomly popping vitamin supplements in pregnancy until further larger study data is available.

References:

https://www.autismspeaks.org/what-autism/facts-about-autism

http://www.cdc.gov/ncbddd/autism/data.html

http://www.fasebj.org/content/30/1_Supplement/151.6.short?related-urls=yes&legid=fasebj;30/1_Supplement/151.6