The Impact of Prenatal Fentanyl Exposure: A Growing Concern

Fentanyl, a powerful synthetic opioid, has become a major public health threat due to its high potential for misuse and its dangerously deceptive nature, contributing to a rise in fatal overdoses over the last decade. Among the most vulnerable populations affected by the opioid crisis are pregnant women and their fetuses. Prenatal exposure to opioids, including fentanyl, poses severe risks to fetal development and long-term health outcomes. As the country scrambles to address the devastating opioid crisis for people with a range of needs – from those who are struggling with substance-use disorders to teens experimenting with drugs for the first time – researchers and clinicians are examining the effects of a woman’s use of fentanyl during pregnancy. A recent 2023 study published in Genetics in Medicine Open yielded preliminary results that associated babies whose mothers used non-prescription fentanyl during their pregnancy with a recurrent pattern of congenital abnormalities.

Opioid Exposure and Fetal Development

Before we get into the details of the study, let’s take a few moments to discuss the more general implications of prenatal opioid exposure. Initially developed for pain management, illicit fentanyl use has surged, contributing to the opioid epidemic. When used during pregnancy, opioids like fentanyl – along with any substance – can cross the placental barrier, directly affecting the developing fetus. The placenta plays a crucial role in nutrient and oxygen transfer from the mother to the fetus. Opioids like fentanyl can impair placental function, leading to restricted fetal growth and low birth weight. These conditions are risk factors for a range of complications, including developmental delays and chronic health issues later in life. We know that fentanyl is approximately 50-100 times more potent than morphine and about 50 times more potent than heroin. A past study revealed that the transfer of fentanyl to the fetus in early pregnancy is quick, even more so than heroin, and remains in the fetal tissue for a prolonged time. Research published in the Journal of Perinatal Medicine shows that opioid-exposed pregnancies often result in preterm births and intrauterine growth restriction (IUGR), both of which can have lasting health impacts. One of the most immediate concerns is Neonatal Abstinence Syndrome (NAS), a condition where newborns experience withdrawal symptoms due to in-utero drug exposure. Symptoms of NAS include tremors, irritability, feeding difficulties, and respiratory issues, often necessitating prolonged hospital stays and medical interventions.

Additionally, a review of twenty-six studies, that looked at over 1400 children prenatally exposed to opioids, indicated cognitive delays that persist into the school-age years. A more recent study comparing the long-term outcome of children ages 4 to 18 years of age with documented prenatal opioid exposure to their biological non-exposed siblings found a 2.1 times increased risk for the need of special education services.  This study is important because through a sibling-based model it controlled for genetics and the home environment as well as 16 other confounding factors, including prenatal exposure to nicotine, alcohol, marijuana and methamphetamine.   In addition, it was shown that the increased risk for special education was not limited to children who had been diagnosed with NAS but was just as high in children with opioid exposure and no diagnosis of NAS in the newborn period.

Study Linking Prenatal Fentanyl Exposure to Novel Syndrome

The recent study published in Genetics in Medicine Open looked at 6 infants at Nemours Children’s Hospital in Wilmington, Delaware along with an additional 4 from other institutions. All 10 infants were born after a pregnancy with prenatal exposure to non-prescription opioids, particularly fentanyl. A pattern of hereditary anomalies was shared among the cases: distinctive facial features, small heads, short stature, feeding difficulties, and physical abnormalities. The study indicates that prenatal fentanyl exposure may have interfered with cholesterol metabolism, which can often indicate Smith-Lemli-Optiz syndrome (SLOS). However, metabolic studies conducted shortly after birth and then again later showed that the abnormal metabolic levels resolved, leading the clinicians to rule out SLOS. Researchers also noted key distinctions when comparing analyses of the infants’ facial features with those of infants with fetal alcohol syndrome (FAS) and Smith-Lemli-Optiz syndrome (SLOS).

The researchers acknowledge the study’s “many significant limitations” including the small sample size, uncertainty about the mothers’ polysubstance use, and the timing and dosage of the fentanyl exposure. Of particular concern would be the lack of information regarding the mothers’ alcohol use during pregnancy.  The authors suggest caution before attributing causality but urge further examination and data replication. Despite the study’s limitations, clinicians feel that including screening and documentation of maternal fentanyl use during pregnancy should be in place, that additional studies are needed, and that long-term follow-up with patients could lead to valuable information about intellectual, behavioral, and physical effects of prenatal fentanyl exposure.

Maternal Health and Prenatal Care

The opioid crisis, exacerbated by the potency of fentanyl, poses substantial risks to pregnant women and their fetuses. Prenatal fentanyl exposure can lead to NAS, neurodevelopmental issues, impaired fetal growth, and a host of long-term health challenges.  Comprehensive care that includes prenatal care, addiction treatment, and mental health support is essential for improving outcomes for both the mother and the baby. Healthcare providers need training to screen effectively for and manage substance use disorder, which includes fentanyl, in pregnant women. Additionally, raising awareness about the risks of opioid use during pregnancy is crucial for prevention.

References

Chasnoff, I.J., Sieger, M.L. (2023).  Prenatal opioid exposure and special education: A sibling study. Advances in Pediatric Research, 10:069, 1-7.

Cooper, J., Jauniaux, E., Gulbis, B., Quick, D., & Bromley, L. (1999). Placental transfer of fentanyl in early human pregnancy and its detection in fetal brain. British Journal of Anaesthesia, 82(6), 929-931. https://doi.org/10.1093/bja/82.6.929.

Wadman, E., Fernandes, E., Muss, C., Powell-Hamilton, N., Wojcik, M. H., Madden, J., Katte Carreon, C., Clark, R. D., Stenftenagel, A., Chikalard, K., Kimonis, V., Brucker, W., Alves, C., & Gripp, K. W. (2023). A novel syndrome associated with prenatal fentanyl exposure. Genetics in Medicine Open, 1(1). https://doi.org/10.1016/j.gimo.2023.100834.

Yeoh, S.L., Eastwood, J., Wright, I. M., Morton, R., Melhuish, E., Ward, M., & Oei, J. L. (2019, July 3). Cognitive and motor outcomes of children with prenatal opioid exposure: A systematic review and meta-analysis. JAMA Netw Open. (7). doi: 10.1001/jamanetworkopen.2019.7025.

Yazdy, M. M., Desai, R. J., & Brogly, S. B. (2015). Prescription opioids in pregnancy and birth outcomes: A review of the literature. Journal of Perinatal Medicine, 43(4), 439-449.