What is the role of obstetric complications in the etiology of autism spectrum disorder (ASD)?

Updated: Sep 30, 2019
  • Author: James Robert Brasic, MD, MPH; Chief Editor: Caroly Pataki, MD  more...
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Many individuals with autism and related conditions experienced untoward events in their prenatal and neonatal periods and during delivery. [12, 13, 14, 56] It is unclear whether the obstetric complications caused autistic disorder or whether autism and obstetric complications resulted from environmental or other problems.

During the perinatal period, the factors associated with autism risk were hypertension or diabetes in mother, threatened abortion, antepartum hemorrhage, caesarian delivery, gestational age ≤ 36 weeks, parity ≥ 4, spontaneous labor, induced labor, no labor, breech presentation, preeclampsia, and fetal distress. During the postnatal period, the factors associated with autism risk were low birth weight, postpartum hemorrhage, male gender, and brain anomaly. [55]

In a large Danish study published in JAMA, maternal use of valproate during pregnancy was associated with a significantly increased risk for autism in offspring. The drug is already not recommended for use in pregnant women due to the risk of congenital malformations and its possible association with low intelligence in children exposed during pregnancy.

Researchers used data on all children born in Denmark between 1996 and 2006. Of the 655,615 children born in the study period, 5437 had autism spectrum disorder, including 2067 with childhood autism. There were 2644 children exposed to antiepileptic drugs during pregnancy, 508 of whom were exposed to valproate. Analysis showed that the children exposed to valproate had a 3-fold increased risk for autism spectrum disorder and a 5-fold increased risk for profound childhood autism compared with unexposed children, even after adjustment for parental psychiatric disease and epilepsy. [57, 58]

The management of women with epilepsy who desire to bear children can be challenging. A woman with an ongoing seizure disorder requires treatment because maternal seizures can result in serious morbidity and mortality for the mother and the fetus. To stop anticonvulsant therapy when a woman with a seizure disorder becomes pregnant to avoid teratologic effects may precipitate uncontrolled seizures that may be fatal to the mother and the fetus. Therefore physicians treating women with child-bearing potential can appropriately initiate frank conversations about future pregnancies. Juvenile myoclonic epilepsy and other seizure disorders typically cause seizures throughout adulthood so pharmacotherapy throughout adulthood is a reasonable treatment plan. While valproate is an excellent agent to control a vast spectrum of seizure disorders, its use in women of child-bearing potential is fraught with danger due to the great risk of producing autism spectrum disorders, spina bifida, and other birth defects. A frank conversation between the physician and the woman of child-bearing potential about the risks and benefits of specific antiepileptic drugs for the mother and the fetus is indicated. Documentation of these conversations is the medical record is needed. This record may be useful in court if legal action is initiated if a child has birth defects.

Exposure of the mother to selective serotonin reuptake inhibitors, particularly during the first trimester, may increase the risk that her offspring will develop an autism spectrum disorder. [59, 60]

Severe, early-gestation maternal hypothyroxinemia is associated with an increased risk of having a child with autism, according to a new study that involved 5100 women and 4039 of their children. Severe maternal hypothyroxinemia early in gestation increased the likelihood of having an autistic child by almost 4-fold. By age 6, children of mothers with severe hypothyroxinemia had higher autistic symptom scores on the Pervasive Developmental Problems subscale of the Child Behavior Checklist and the Social Responsiveness Scale. [61, 62]

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