Promoting Primary Prevention of Neonatal Abstinence Syndrome

By | March 21, 2021

“Neonatal abstinence syndrome” (NAS) sounds deceptively innocuous, given that it is literally infant drug withdrawal. It is usually caused by prenatal exposure to opioids but can also result from maternal consumption of other substances, like alcohol and antianxiety medications. Common symptoms include excessive high-pitched crying, fever, sweating, irritability, vomiting, diarrhea, rapid breathing, sleep disturbances, and poor weight gain. Nearly one-third of infants diagnosed with NAS suffer serious respiratory complications. Some substances that do not cause a definable withdrawal syndrome, such as cocaine and methamphetamine, can harm fetuses and increase the risk for and severity of withdrawal in offspring of polysubstance users.

Estimates for the proportion of NAS diagnoses among infants born to opioid-dependent mothers vary but are likely between 21% and 82%, reflecting not only variation in pharmacological exposures but the myriad of interrelated factors that affect health outcomes. NAS is a serious and rapidly growing problem across the U.S., with a pattern reflective of the country’s evolving opioid epidemic. Between 1999 and 2013, national NAS incidence more than tripled.

Long-term consequences of NAS are still largely unknown. The results of maternal drug use on downstream outcomes are difficult to ascertain due to the near impossibility of teasing apart various developmental influences, including multiple prenatal drug exposures, other pre- and postnatal physical exposures, genetics, and social determinants. However, chronic opioid exposure during gestation is associated with reduced Mental Development Index scores at 12 and 18 months and delays in early developmental milestones like sitting independently and crawling. Children diagnosed with NAS after birth exhibit poorer school performance in adolescence than children without a NAS diagnosis, with disparities increasing over time even after adjusting for potential confounders.

Surprising to some is the fact that medications commonly used to treat opioid dependence cause NAS. However, medication-assisted treatment (MAT) greatly improves prospects for opioid-dependent mothers and their offspring. In fact, maintenance treatment with opioid agonists such as buprenorphine and methadone is recommended over medically supervised tapering during pregnancy, despite the fact that this often results in NAS.

A frustrating feature of many discussions related to NAS is that they tend to focus exclusively on the importance of screening pregnant women for opioid dependence and getting those who need it into treatment (see here, here, and here), along with strategies aimed at improving care for infants diagnosed with NAS (see here and here). While those are certainly laudable goals, my sense is that not nearly enough attention is paid to preconception interventions, especially those aimed at preventing unintended pregnancies among opioid-dependent women.

At the pharmacy where I’ve worked during graduate school, I’ve frequently processed buprenorphine prescriptions for pregnant women. Many were coming in to fill MAT prescriptions long before becoming pregnant. I have the distinct impression that contraception is rarely, if ever, discussed between local MAT providers and their patients. Addiction specialists don’t just prescribe medications to treat opioid dependence. They regularly prescribe antidepressants, non-opioid pain relievers, anti-anxiety medications, and even antihypertensives. Yet I’ve never seen prescriptions written by addiction specialists for contraceptives, and I’ve encountered many women who became pregnant during treatment. While some of their pregnancies may have been planned, research suggests that the majority were likely not. Women receiving MAT are at elevated risk for unintended pregnancies, with reported rates exceeding 80%, compared to just 45% among women in the general population.

A few simple strategies could prove effective in preventing at least some cases of NAS. These suggestions are informed by a human rights-based approach [pdf] to sexual and reproductive health. At a minimum, they will ensure that women receiving MAT are exercising informed consent if they should choose to refrain from taking steps to avoid pregnancy.

  • Prescribers at narcotic treatment facilities (authorized to dispense methadone) and DEA-registered prescribers of buprenorphine should complete NAS provider education as part of DEA certification.
  • Facilities and prescribers should provide every female patient of reproductive age with objective information about NAS. It is paramount that this be provided in a nonjudgmental, patient-centered manner that respects patients’ reproductive autonomy.
  • Female patients of reproductive age should be required to sign an acknowledgement form. The language should balance the goal of preventing NAS with the need to honor individual reproductive rights. A model form is provided below.

This form has two parts, each of which must be completed in order to receive medication-assisted treatment through this office.

1) Sign after the following statement:
“I am aware that if I carry a pregnancy to delivery while taking this medication, the baby may be born physically dependent on it and experience withdrawal.”
Patient signature___________________________

2) Initial in the space next to one and only one of the following statements:
“As a female of childbearing age, I certify that …”
____ “I am currently pregnant and under the care of an obstetric provider who is aware that I am taking/seeking this medication.”
____ “I am currently pregnant and under the care of an obstetric provider, and I authorize this office to inform that provider that I am taking/seeking this medication.”
____ “I am currently pregnant but not yet under the care of an obstetric provider. I authorize this office to arrange a referral to a family planning clinic that can offer options counseling and connect me to obstetric care or abortion services.”
____ “I am not pregnant and am currently using a birth control method to prevent pregnancy.”
____ “I am not currently pregnant but am choosing not to use birth control. I am aware of the potential harm the medication I am taking/seeking may cause to my baby should I become pregnant and give birth while taking it.”[1]

Such a form would not be unprecedented; many medical practices require patients to sign controlled substance agreements in order to receive controlled substance prescriptions from their providers. Further, requiring female MAT patients to complete the above form would impinge far less upon their reproductive autonomy than the current federal requirements that must be met by women seeking isotretinoin-containing medications (e.g., Accutane) to treat acne. The iPledge program explicitly requires [pdf] that female patients who can become pregnant undergo pregnancy tests and use 2 separate birth control methods for at least 1 month before, during, and for 1 month after completing treatment with one of the restricted medications.

Finally, contraceptive access must be ensured for all women receiving MAT. Addiction treatment specialists should offer their patients contraceptive prescriptions as standard practice and partner with local family planning providers to ensure access to a broad range of contraceptive methods – including long-acting reversible contraceptives (LARCs) – and comprehensive reproductive health services. Annual hospital charges billed to Medicaid for NAS were over $1.2 billion as of 2012, so the economic rationale for funding family planning services to prevent NAS-affected pregnancies is obvious.

Would these suggestions prevent all cases of NAS? Not even close. But it would be a start.

[1] In this case, the patient should be referred to a family planning provider for preconception counseling and care.

Barbie Zabielski

Barbie Zabielski

Barbie Zabielski received an MPH from The George Washington University in August 2017. She has a wide range of interests in public health, including environmental epidemiology, pharmacovigilance, Alzheimer’s disease and other neurodegenerative disorders, and autoimmune conditions. Her primary focus, however, is sexual and reproductive health in low-resource settings. She is deeply committed to promoting increased access to and utilization of modern contraceptives as a means of improving social, economic, health, educational, and environmental outcomes among diverse populations across the globe. She currently works with New River Health District on developing various aspects of its family planning program.
Barbie Zabielski

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