Discoveries and Data: Exposures and Risk Factors

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pic_sr_pills-3880187CORTICOSTEROIDS AND CLEFTS

Limited human data exists about corticosteroids, drugs such as cortisone and prednisone (used to treat asthma, autoimmune diseases and inflammation). Experiments in laboratory animals linked the medications to oral clefts but reviews of scattered case reports concluded there was little risk in humans.

We asked about corticosteroid use around conception and in early pregnancy in interviews with over 2000 mothers. We found:

bullet-5882605 Corticosteroid use was linked with a 4-5 times increase in risk for oral clefts.
bullet-5882605 Risk was unchanged for conotruncal heart defects, neural tube and limb defects.

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OVER-THE-COUNTER DRUGS AND GASTROSCHISIS

Reduced blood supply to the developing abdominal wall is thought to cause gastroschisis, a life-threatening condition where the intestines protrude from a hole near the umbilical cord.

bullet-5882605 Mothers taking aspirin or ibuprofen had a 4-5 time higher risk. These medications are strong cyclooxygenase inhibitors, active in pathways that decrease blood flow. Acetaminophen, which works by a different mechanism, showed no association with gastroschisis.
bullet-5882605 Decongestants, particularly pseudoephedrine and phenylpropanolamine, more than doubled the risk. (Both are blood vessel constrictors.)
bullet-5882605 Antibiotic use lowered risk. There was no association for anti-nausea medications.
bullet-5882605 The extra risk found with various medications was not due to mothers’ reasons for taking the drugs. Neither illness nor fever was associated with gastroschisis.

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DEFECTS IN 25% OF BABIES EXPOSED TO ANTI-ACNE DRUG

Accutane (isotretinoin)—prescribed for severe acne—is a synthetic derivative of the retinol form of vitamin A. Exposed pregnancies are more likely to be miscarried or stillborn; about 25% of liveborn children will have major birth defects of the heart, thymus gland, face/ears, skull and brain. (In animal experiments, Accutane interferes with neural crest cell migration—movement of cells that originate around the neural tube (spinal cord) and contribute to the developing heart, thymus and face.) Older children have orthodontic problems and are at risk for developmental disabilities or learning problems.

These findings led to stringent guidelines for prescribing Accutane to women: they must be thoroughly warned of the birth defects risk, have a negative pregnancy test and use a reliable birth control method while taking the medication.

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NITRATE-RELATED DRUGS AND NEURAL TUBE DEFECTS

We identified a number of medications that metabolize to nitrate-like compounds in the body. Taking these medications did not change risk for neural tube defects.

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