It’s long been known that medication-assisted treatment (MAT), with adequate doses of methadone or buprenorphine, can stabilize women during pregnancy and prevent relapse. But a key question has confronted the addiction-treatment field for years: If mothers-to-be undergo MAT, will it affect their unborn babies?
The MOTHER Study, an ongoing investigation that began in May 2005, was designed to answer that question and related issues. Papers published in 2010 and 2012 specified the protocol and procedures for subsequent MOTHER studies (see References, below).
The recently completed segment of the study, summarized below, compared outcomes in babies exposed before birth to methadone or buprenorphine, and to infants who required treatment for neonatal abstinence syndrome (NAS), to those who did not require treatment, from birth to age three. Drug and Alcohol Dependence posted the results on February 1.
Key Findings:
Children exposed to methadone or buprenorphine before birth followed a three-year path of normal physical and mental development.
Children who required treatment for NAS did not differ in developmental outcome from children who did not require treatment.
Details of the MOTHER Study
AT Forum interviewed the lead author of the current study, Karol Kaltenbach, PhD, and a co-author, Hendrée Jones, PhD, the lead author of the MOTHER randomized controlled trial. Both have been at the forefront of the MOTHER study since its beginning.
Below is a summary of the current study, and highlights of a discussion with the study’s authors.
Summary of Results
The research team found that the severity of NAS did not adversely impact early childhood growth and development. Measured at three years, development was normal in the broad areas of physical growth, cognition, and language. (See a related article in this issue, “When Mom is Better Than Morphine . . . ” discussing optimal treatment of NAS.)
Mothers Had “Minimal to No” Substance Use
The published article noted that the MOTHER sample was unique in that there was minimal or no prenatal exposure to alcohol or other substances, except tobacco.
We commented, “Such good control of substance exposure wasn’t typical of other studies, was it?”
Karol Kaltenbach, PhDIt wasn’t. Planning was the key, along with the strict inclusion and exclusion criteria followed in the MOTHER study. “We didn’t enroll anyone who misused alcohol or benzodiazepines,” Dr. Kaltenbach said. She explained that an average methadone dose back in the 1980s was 42 mg—”but that amount was based on flawed studies,” and often amounted to underdosing—so, for relief, patients tended to turn to other opioids, barbiturates, and benzodiazepines. “But no one today uses average methadone doses that low.”
To help verify their patients lack of exposure to other drugs, the team collected urine samples three times a week and analyzed them for evidence of alcohol or other drugs.
Motivation helped, as well. “We had an extremely effective voucher system,” Dr. Kaltenbach said. “Mothers who entered the study early, and had urine test results that consistently showed no illicit drug use, could earn vouchers to use for baby supplies, household items, rental deposits, etc.”
Other Studies, Other Findings
If the MOTHER study babies have done so well, physically and mentally, why have other studies reported or suggested problems? These include vision, motor, and behavioral difficulties; genetic variations; sleep disturbances; ear infections; and cognitive problems.
We asked for specifics.
The authors explained that the variability in results and in the interpretation of results may be due to the design and methods of other studies. If important factors of the prenatal and postnatal environment are not measured or accounted for, different conclusions are drawn.
Detoxification
When asked if it’s safe to withdraw methadone or buprenorphine during pregnancy, Dr. Kaltenbach answered, “The real question is not if it’s safe, but whether you should do it. If the mother is misusing drugs and goes into withdrawal, the fetus will go through withdrawal, too.”
Dr. Jones agreed. “Detoxification doesn’t work well for the vast majority of women who aren’t pregnant—so why would it work any better for pregnant women?
“The relapse rate is incredibly high, 85%, one month after detoxification. If the goal of detoxification during pregnancy is to avoid NAS—the collective published data show that some proportion of babies continue to have it. Thus, detoxification does not avoid NAS.”
And why is withdrawal such a controversial issue?
Dr. Kaltenbach explained that some people think that withdrawing the mother from all drugs will mean the baby will not have NAS. “But now, the mother is at risk of relapse.
“NAS can be treated. And we have evidence that it doesn’t cause long-term deficits. But if the mother returns to the substance she’d been taking, and takes the same dose, she could have a fatal reaction.”
# # #
Hendrée Jones, PhDAfter discussing the main topics of the three-year study, the authors delved into something close to their hearts—the importance of seeing the mothers as people, rather than subjects who misuse drugs, or participants in a study. They commented briefly on the lives the study mothers lead, and the difficulties they face.
Fears
“Even with a plan of safe care, many women fear that Child Protective Services will automatically remove their children,” Dr. Jones said. “But Child Protective Services is an ally; they don’t want to take the baby. It’s expensive, and lots of paperwork is involved. Their aim is to remove children only if it’s really unsafe for them to be living as they are.”
Judgments
Dr. Kaltenbach offered an example of judgmental framework. Factors affecting how severe opioid withdrawal will be include the mother’s alcohol use, benzodiazephine use, and cigarette smoking. None of the three by itself will cause NAS severe enough to require treatment. But, when combined with opioid discontinuation, any one of them could make the withdrawal process take more time or be more severe.
The problem, she said, comes when the mother’s use of these substances “is interpreted in a judgmental framework—a mother uses illegal drugs, so we have to protect her baby from her. Instead, we should focus on what we can do to improve the mother’s condition, so she can have a healthy baby, and can be a healthy mother for her baby.”
The Mother-Infant Dyad
“Too often, people want to separate the mother and infant dyad,” Dr. Kaltenbach said. “They focus on . . . well, the mother uses illicit drugs, so . . . she’s a bad person; we must save the baby.”
Instead, she said, we need to provide for the mother and the infant together. “We need a healthy mother in order to have a healthy infant.” Providing the mother with comprehensive treatment means she will receive prenatal care and addiction treatment, she said, and babies usually go to term.
“It’s a much different outcome if the mother is on the street, using an illicit substance. You can have NAS in both situations, because opioids cross the placenta. But the rest of the environment is very different. One is very supportive; the other is very dangerous.”
The Whole-Person View
“There seems to be a hyper-focus on looking for the negative long-term developmental effects among children exposed to opiates before birth,” Dr. Jones said. The approach she and Dr. Kaltenbach prefer is the that of the “whole person.”
“We need to be looking at factors of poverty, trauma, poor nutrition, dehydration, and chronic severe, toxic stress in our women. And looking at social determinates of health, in terms of our ability to predict risk and resilience for the children. We need to take a more holistic approach.”
# # #
References
Kaltenbach K, O’Grady KE, Heil SH, et al. Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes. Drug Alc Depend. 2018;185:40-49. doi: https://doi.org/10.1016/j.drugalcdep.2017.11.030.
Jones EJ, Kaltenbach K, Heil SH. Neonatal Abstinence Syndrome After Methadone or Buprenorphine Exposure. NEJM. 2010; December 9;363(24):2320-31. doi: 10.1056/NEJMoa1005359.doi: 10.1056/NEJMoa1005359.
Jones EJ, Fischer G, Heil SH, et al. Maternal opioid treatment: Human experimental research (MOTHER) – Approach, issues, and lessons learned. Addiction. 2012;November;107(0.1):28-35. doi: 10.1111/j.1360-0443.2012.04036.x.
# # #