The maternal quadruple (Quad) screen is performed during the second trimester of pregnancy as a risk assessment for Down Syndrome (Trisomy 21; T21), Edwards’ Syndrome (Trisomy 18; T18), and neural tube defects (NTDs). Four analytes – alpha fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A– are measured and used along with patient health information (age, weight, pregnancy history, smoking history, etc.) to determine the risk of the fetus having T21, T18 or NTDs. The Quad screen is recommended for women who have a family history of birth defects, are 35 years or older, used certain medications during pregnancy, or have diabetes and use insulin, as these factors can increase risk of these pregnancy disorders. The Quad screen is a preferred method of screening before other invasive procedures and may indicate that further testing should be performed.

Although smoking does not increase the risk of T21, T18 or NTDs, smoking during pregnancy can influence measured concentrations of the analytes used in the Quad screen risk assessment. As such, the College of American Pathologists Laboratory Accreditation Program recently introduced a requirement to solicit current smoking status on both prenatal screening requisition forms (CHM.32350) and reports (CHM.32300) (1). Using smoking history, Quad screen calculations can be adjusted to avoid misinterpretation of results, thereby providing a more accurate assessment of risk. There are pitfalls to this approach, however, due to possible inaccuracies in reported smoking history which can cause further misrepresentation of Quad screen results.

So how reliable are patient disclosures of smoking status? The Centers for Disease Control and Prevention (CDC) reports that the prevalence of cigarette smoking at any time during pregnancy is 1 in 14 or 7.2% (2). Data from our retrospective analysis showed smoking rates similar to these estimates provided by the CDC. When comparing disclosed smoking status to measured nicotine and metabolites in our Quad screen patient population, we found that active smoking rates appear to be lower in disclosed smokers. Conversely, active smoking rates were higher in disclosed non-smokers and those with unreported smoking status.

There could be various reasons for the inconsistency between disclosed smoking rates and measured nicotine and metabolites in patients. Possible causes could include issues with paperwork logistics, the sensitivity and comfort of the patient to disclose this information, differences in smoking frequency and metabolism, or the fact that patients may partially or fully abstain from smoking during pregnancy but still consider themselves smokers. Regardless of the reason, patient compliance of correctly disclosing current smoking status is critical for making maternal screening adjustments. Laboratories need to be aware of the possible inaccuracies when obtaining smoking history of patients. Clinicians can help this effort by stressing the importance of correctly reporting patient demographic information including smoking status.


  1. Chemistry and toxicology checklist. College of American Pathologists: CAP Accreditation Program, 2017.
  2. Drake P, Driscoll AK, Mathews TJ. Cigarette smoking during pregnancy: United states, 2016. NCHS Data Brief, no 305. Hyattsvill, MD: National Center for Health Statistics. 2018.