Smallest, Largest Infants Show Higher Autism Risk

Nancy A. Melville

February 13, 2012

February 13, 2011 (Dallas, Texas) — Infants born in the lowest and the highest percentiles of birth weight have an increased risk for autism, according to research presented here at the Society for Maternal-Fetal Medicine 32nd Annual Meeting.

Premature birth and low birth weight have each been associated with an increased risk for autism. The researchers sought to better understand the specific risks.

"Previous studies have looked at gestational age and weight at birth, but few have looked at extremes of birth weight, and none have looked at these extremes by gestational age," said one of the researchers, Cheryl Walker, MD, assistant professor, Department of Obstetrics and Gynecology, University of California at Davis.

The researchers accessed a California database of nearly 6 million births from 1991 to 2001, and analyzed the annual 5th, 10th, 90th, and 95th birth-weight percentiles according to sex and gestational age at birth.

Additional data from the California Department of Developmental Services indicated that 20,206 children from the birth cohort were later diagnosed with autism.

Information on the birth weight and gestational age of the infants revealed that the risk for autism was significantly higher in infants who were extremely small for gestational age (95% percentile; adjusted odds ratio, 1.12; 95% confidence interval, 1.05 to 1.19). The risk in infants who were large for gestation age was even higher; in the 95% percentile, there was a 21% increased risk for autism.

Interestingly, although preterm infants (before 34 weeks) in the small-for-gestational-age group and term infants (39 to 41 weeks) in the large-for-gestational-age group had a higher risk for autism, premature infants who were large for their gestational age had no increased risk.

"That finding may relate to uncertainty in gestational age in the data, but the other findings point to the pathophysiology of placental function, particularly as the risk increased proportionally to degree of being small for gestational age," Dr. Walker explained.

The critical role of the placenta in brain development, in particular, might be compromised, thereby laying the groundwork for a disorder such as autism.

"Placental function seems integral to the equation, with the availability of nutrients and oxygen that determine overall growth having a broader influence than we thought, particularly at its extremes, on neurodevelopment," Dr. Walker said.

Other mechanisms that could play a role in increasing the risk in large-for-gestational-age infants could include underlying maternal obesity and its complications (such as diabetes, hypertensive disorders, and metabolic disorders), resulting neonatal or infant metabolic dysfunction, or more difficult birth or birth trauma, Dr. Walker said.

Risk factors related to being small for gestational age could include placental restriction with limited availability of oxygen and nutrients, leading to mild acidosis.

"These are hypotheses for us to test," Dr. Walker said.

Until more is understood about the risks, clinicians should at least monitor children born prematurely and small for their gestational age or at term but large for their gestational age for potential delays and deviations in neurodevelopment, she added.

"Our findings lend support to interventions aimed at encouraging women to enter pregnancy at a normal body weight and to maintain an appropriate weight gain throughout gestation."

According to George Saade, MD, professor and chief of obstetrics and gynecology at the University of Texas Medical Branch in Galveston, the uterine environment is a logical culprit when patterns emerge between infant weight at gestational age and conditions such as autism.

"If the uterine environment is not normal, either because the growth is delayed or accelerated, then mechanisms involved in autism may be activated," said Dr. Saade.

"I would say that these are novel and interesting findings that should be evaluated further," he added.

"The findings should be confirmed in other datasets to make sure that the association is not due to factors that were not evaluated. It would also be important to test this finding prospectively by following children born too small or too large."

The authors and Dr. Saade have disclosed no relevant financial relationships.

Society for Maternal-Fetal Medicine (SMFM) 32nd Annual Meeting: Abstract 42. Presented February 10, 2012.

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