Promoting Primary Prevention of Neonatal Abstinence Syndrome

By | October 19, 2017

“Neonatal abstinence syndrome” (NAS) sounds deceptively innocuous, given that it is literally infant drug withdrawal. It is usually caused by prenatal exposure to opiates 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 widely; an oft-cited range is 55-94%, 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 opiate epidemic. Between 1999 and 2013, national NAS incidence more than quadrupled.

Long-term consequences of NAS are 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 opiate exposure during gestation is associated with reduced Mental Development Index scores at 12 and 18 months, as well as delays in early developmental milestones like sitting independently and crawling.

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 opiate agonists such as buprenorphine and methadone is recommended over medically supervised tapering during pregnancy, despite the fact that this results in NAS in the majority of instances.

A frustrating feature of many discussions related to NAS is that they tend to focus 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 laudable goals, my distinct impression is that not nearly enough attention is being paid to preconception interventions, especially those aimed at preventing unintended pregnancies in women receiving MAT with drugs like buprenorphine and methadone.

At the pharmacy where I’ve been working during graduate school, I frequently process buprenorphine prescriptions for pregnant women. Many were coming in to fill MAT prescriptions long before becoming pregnant. I do not understand why their treatment providers failed to convey to them the importance of using contraception, or if they did, why there was no formal referral to family planning services or provision of contraceptive prescriptions by the treatment providers themselves. Addiction specialists don’t just prescribe medications to treat opioid dependence. They regularly prescribe antidepressants, non-opiate pain relievers, antianxiety medications, and antihypertensives. Yet I never see prescriptions written by addiction specialists for contraceptives. I am also skeptical that overt discussions about the importance of taking steps to prevent pregnancy during treatment are common.

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 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 precautions to avoid pregnancy.

  • 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 patient with information about the condition.
  • 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 should I carry a baby to delivery while taking this medication, the baby will be physically dependent on this/these medication(s) and likely to suffer 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 who I authorize this office to inform that I am taking/seeking this medication.”
____ “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.”


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 isotretonin-containing medications (e.g., Accutane) to treat acne. As described in the Patient Introductory Brochure, the iPledge program explicitly requires that female patients who can become pregnant undergo pregnancy tests and use birth control 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 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 wisdom of funding family planning services to prevent NAS-resulting pregnancies is obvious.

Would these suggestions prevent all cases of NAS? Of course not. But it would be a start.

Barbara Zabielski

Barbara Zabielski

Barbara 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.
Barbara Zabielski

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