The opioid crisis in the US is an urgent public health emergency that requires instant action to protect vulnerable individuals. While the startling death toll associated with this epidemic has received much attention, the health outcomes associated with prenatal opioid exposure during pregnancy are less well defined.
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As the population continues to grow, so does the use and misuse of opioids during pregnancy. In 2014, the number of women with an opioid use disorder at delivery hospitalization, was four times greater than in 1999.
Right now, the number one question mothers, fathers and clinicians have when they see that a mother is using opioids while pregnant is how will this opioid exposure affect the child's health? We cannot answer that question right now with the existing data that we have."
Elisabeth Conradt, Developmental Psychologist, University of Utah
As part of a National Institutes of Health (NIH) initiative to investigate the effects a child's environment has on their life outcomes, Conradt and her colleagues have now collected and reviewed 52 publications to establish what is understood so far about how opioid exposure during pregnancy affects future childhood outcomes and development.
Neonatal opioid withdrawal syndrome
One immediate and visible impact of the prenatal opioid exposure is neonatal opioid withdrawal syndrome (NOWS). The condition is diagnosed within a few days of birth, with symptoms including difficulty feeding, tremors and high-pitched crying. However, little is known about how NOWS may affect a child’s neurological development in the future.
The main question people are currently asking, says Conradt, is similar to the one asked during the 1980s and 90s about prenatal exposure to crack cocaine:
"What we actually found is that the effects of cocaine on these child outcomes were quite subtle. Cocaine was probably a proxy for the type of environment in which the kids were raised."
For the current review, which was published in the journal Pediatrics, Conradt and colleagues paid particular attention to studies looking at children diagnosed with NOWS.
They found that studies of infants born with the condition generated conflicting findings. Some demonstrated differences between infants exposed to buprenorphine in the womb and those exposed to methadone. Both drugs are given to treat opioid addiction, but buprenorphine is the one that has been approved to treat pregnant women.
While some of the studies demonstrated fewer NOWS symptoms in newborns that had been exposed to buprenorphine, others showed no significant differences between those exposed to buprenorphine and those exposed to methadone.
Conradt says that because the data were so tenuous and the findings so inconsistent, no conclusions could reliably be drawn, meaning it is not yet clear what the effects of prenatal opioid exposure are at birth.
Effects of prenatal opioid exposure during infancy
Twenty-one of the studies looked at childhood development up to 2 years following prenatal exposure. Conradt says many of those studies only looked at small groups of children, making it difficult to tell whether any effects were due to opioid exposure or other confounding factors.
One study including 131 infants was large enough to control for confounding factors and that found many null effects of opioid exposure on cognitive and behavioral outcomes
"We felt a little bit more comfortable saying that there may not be major effects of prenatal opioid exposure in infancy after controlling for these relevant confounders," says Conradt.
Effects on development beyond 2 years of age
After reviewing 27 studies looking at the effects on cognitive development beyond 2 years, the researchers also found that results were inconsistent. Some studies reported significant impacts on IQ and language ability, while others found no such effects.
For behavioral outcomes, on the other hand, findings were more consistent. Children who had been exposed to methadone experienced increased fear, anxiety and aggression. In addition, a diagnosis of NOWS was linked to decreased attention.
Conradt thinks it is not surprising that such effects would emerge as children age, since growing up presents more challenges such as having to pay attention in class, having to sit still and having to control yourself: “It's not surprising that kids exposed to methadone in the womb may have a harder time with those skills."
However, it is difficult to tell whether these behavioral impacts are directly linked to prenatal opioid exposure, to a child’s environment or to an interaction between the two over time, she adds.
Further research will be vital
One of the main take-home messages of the researchers’ work is that the existing data is limited by small study populations and the presence of confounding factors that make it difficult to determine the true effects of opioid exposure.
An initiative called the Environmental Influences on Child Health Outcome (ECHO) program, which Conradt is involved in, has been set up in an effort to resolve these problems. This nationwide program, which is supported by the NIH, is aimed at enhancing children’s health.
The goal of the seven-year, 71-cohort study is to establish which environmental factors before and after birth affect children’s development.
We have the opportunity to collect data on over 50,000 children across hundreds of different sites across the country, and tracking their outcomes in a systematic and rigorous manner,."
As one of the ECHO researchers, Conradt, will use the data as it becomes available to continue trying to establish exactly what prenatal opioid exposure means for children in the future.
Honein, M. A., et al. (2019). Public Health Surveillance of Prenatal Opioid Exposure in Mothers and Infants. Pediatrics. https://pediatrics.aappublications.org/content/143/3/e20183801