A dramatic increase in heroin and painkiller use in the Cincinnati, Ohio area worried Scott Wexelblatt, MD, a neonatologist at Cincinnati Children’s Perinatal Institute, leading him to spearhead a regional universal drug screening program for moms delivering at Cincinnati-area hospitals. Launched in September 2013, the program, which involves dual screening of mothers and their newborns, has been embraced by the Greater Cincinnati Health Council and has become one of the most visible of such programs in the United States. Others are watching it closely as they grapple with an exponential rise in both illicit and prescription drug abuse and a lack of clear guidelines for testing.
A study Wexelblatt led between 2012 and 2013 found 5.4% of all mothers had a positive drug test on admission and 3.2% of the mothers tested positive for opioids. “Opioids are what we worry about most,” he explained. “Among newborns exposed to opioids in utero, between 55 percent and 94 percent develop withdrawal signs—and 30 to 80 percent of those need pharmacologic treatment.”
Early diagnosis and treatment achieves the best outcomes. Babies with neonatal abstinence syndrome (NAS) often are irritable, feed poorly, and have diarrhea and seizures. Adverse long-term outcomes are less well studied, but neonatologists fear that kids in homes with substance abuse might suffer from child abuse, experience growth problems, and miss normal childhood milestones.
Universal Screening in Cincinnati
In Cincinnati’s universal screening program, participating hospitals encourage mothers to consent to testing. If mothers do not consent, their babies are tested instead. When possible, pregnant women identified with substance abuse problems are referred to addiction services. Opioid-exposed newborns may need longer stays in the hospital, especially if they are suffering from withdrawal and need pharmacologic care.
Cincinnati hospitals use urine immunoassays for initial screening, followed by mass spectrometry to validate results, according to Wexelblatt. Cincinnati Children’s mass spectrometry laboratory tests for 47 drugs of abuse in urine in a 6-minute analysis, he explained. “If samples arrive in our lab by 10:30 in the morning, we can get out reports by the end of the day.”
On the National Front
Elsewhere around the nation, drug toxicology screening programs for pregnant women and newborns continue to expand. Yet strong evidence-based guidelines for drug screening and referrals in this population are wanting. This absence was recognized at the federal level in November, when President Obama signed the Protecting Our Infants Act. It directs the Department of Health and Human Services (HHS) to identify and make available recommendations for preventing and treating prenatal opioid use disorders, and diagnosing and treating NAS specifically. Additionally, the act authorizes HHS to evaluate and coordinate federal efforts in research, response to NAS, and to assist state health agencies with data collection.
Absent clear guidance, a patchwork of state- and hospital-specific practices prevail, from universal versus targeted screening, maternal urine screening versus urine, meconium, or even umbilical cord specimens from babies. Hospitals also differ in when to initiate confirmatory testing and how to communicate positive results.
The Case for Universal Screening
Many experts favor universal screening rather than risk-based screening. With the latter, “you are making a lot of assumptions and it tends to unfairly target low-income women,” suggested Jessica Young, MD, assistant professor of obstetrics and gynecology at Vanderbilt University in Nashville. “Risk-based screening is not the recommendation of [the American Congress of Obstetrics and Gynecology (ACOG)],” said Young. “ACOG recommends universal drug screening during prenatal care using a validated screening tool, such as the widely used 4P’sPlus.” The tool uses five questions to determine risk for substance abuse during pregnancy. A urine drug test is recommended, with patient consent, if the screen points to drug abuse.
“Urine drug testing can be a useful tool. However, because of the importance of patient consent and false positives, it is important that there be appropriate consent processes in place, as well as confirmatory results,” explained Young. The American Academy of Pediatrics also advocates a similar position.
A March 2013 survey of drug screening at institutions across Ohio found that 88% of maternity level 1 (basic) maternity care facilities favored universal screening, as did 75% of both level 2 (specialty) and level 3 (subspecialty) institutions, according to Steven Cotten, PhD, DABCC, assistant professor of pathology and associate director of chemistry and toxicology at Ohio State Wexner Medical Center in Columbus.
Despite the interest in universal screening, there is support for targeted screening as well, based on cost and feasibility considerations. “Universal screening is extremely expensive and diagnostic yield is poor,” observed Gwen McMillin, PhD, director of the toxicology laboratory and pharmacogenetics at ARUP Laboratories in Salt Lake City. In a study ARUP did in conjunction with the University of Iowa, drug testing—either urine or meconium or both—was ordered in 36% of live births. Of the cases involving meconium specimens, only one-quarter tested positive for one or more drugs or drug metabolites.
What’s the Best Specimen?
Perinatal drug testing aims to examine in utero drug exposure over the pregnancy. Each type of specimen has its own advantages and limitations. Selection of one specimen over another may be guided by unique workflow at an institution and access to timely laboratory readings. Absent post-delivery problems, neither moms nor newborns typically stay long after delivery, placing a premium on speedy turnaround times.
In testing mothers, urine is the most common sample type, followed by hair, which offers a longer window of detection, enabling assessment of chronic drug use, said experts. Newborn hair develops during the last trimester, permitting detection of drug exposure up to as much as 3 to 4 months. However, using hair as a specimen has drawbacks, too. For example, studies have shown that hair color affects drug test results, with black hair accumulating more drug, according to McMillin.
“Most hospitals do maternal urine screening, but urine doesn’t pick up chronic use,” she explained. Urine testing also is prone to false positives, limiting its clinical use. However, because urine testing produces rapid results, it provides key advantages in cases where the mother requires closer monitoring for abuse.
Meanwhile, urine as the specimen type for newborn testing poses more challenges. Newborn urine can be easily contaminated, obtaining it is invasive, and false positives limit its clinical use. The Cincinnati program is learning as it grows, and is moving towards using meconium and cord tissue samples, which permit a lookback of between 14 and 20 weeks.
Other laboratorians prefer meconium samples for newborn screening. Indeed, Cotten considers meconium the gold standard specimen type because of its long window of detection back in the pregnancy. While McMillin concurred about this advantage, she cautioned that the extraction technique can influence sensitivity, and specific drug metabolites in meconium may result in discrepant findings between maternal and newborn tests.
Cotten added that cord tissue is an emerging specimen of considerable interest, but more studies about it are needed. “For babies who are exposed, you can get the cord tissue up to your lab right at delivery, potentially saving hours,” he said.
Whatever the biological specimen used, laboratorians concur that mass spectrometry is the gold standard for confirming a positive screening result. In fact, many do not even report positive screening results unless they have been verified with mass spectrometry, Weill Cornell Medicine in New York City among them.
“It is very important for laboratorians to recognize that there are substantial implications in reporting false positives. My strong opinion is that the harms of sharing non-confirmed positive urine screens far outweigh the benefits,” said Joshua Hayden, PhD, DABCC, FABC, Weill Cornell’s director of toxicology and therapeutic drug monitoring and assistant director of the central laboratory.
The necessity for robust policies and procedures has taken on new importance as some states, including Alabama, South Carolina, and Tennessee, have moved to criminalize drug use during pregnancy. However, providers consulted for this article all favor working cordially with the mother, establishing and maintaining rapport so that affected mothers and children get the best treatment, and never punitively.
As William Clarke, PhD, associate professor of pathology and director of clinical toxicology at Johns Hopkins University in Baltimore put it, “The gold standard for confirmatory testing is gas chromatography-mass spectrometry. Without confirmation, we are at risk of potentially falsely engaging the parents. Even if the initial assay is correct, confirmatory testing is essential if there is a chance the result is needed for legal reasons.”