Split Dosing of Methadone May Reduce NAS

I just read a new article (McCarthy et al, Journal of Addiction Medicine, Vol. 9, (2), pp105-110, March/April 2015) on methadone dosing during pregnancy. This study’s data showed reduced incidence of withdrawal in babies born to moms on divided doses of methadone compared to once-daily dosing. This data also showed reduced incidence of withdrawal in these moms on higher total doses of methadone compared to what we have seen in the past with lower maternal doses.

Current practice is to adjust the maternal dose of methadone according to how she feels. If she has withdrawal signs and symptoms, we increase her dose. We assume that if the mother’s at an adequate dose, the fetus should be doing OK too. We know reduced dosing of methadone during pregnancy is not recommended due to higher relapse rates in the mom, and worse fetal and maternal outcomes. Additionally, past studies showed no clear relationship between the maternal methadone dose and the likelihood of neonatal abstinence syndrome (NAS). In other words, increased maternal dose doesn’t increase the incidence or severity of withdrawal in the newborn.

However, we also have past studies which showed a significant decrease in fetal heart rates and fetal movement during times of peak methadone levels (several hours after dosing), compared to fetal heart rates and movement during times of trough blood levels (end of the 24-hour dosing cycle). Those studies showed more normal fetal heart rates and movement after splitting the total dose into equal doses, which is called split dosing. Due to this data, many opioid treatment program doctors have been trying to split the mom’s total methadone dose into two halves, a morning and evening dose.

The authors of this new study decided to build on past data and look at more than once-daily dosing of methadone during pregnancy. They also increased the total dose of methadone to treat any maternal report of withdrawal.

The study is a bit complicated. It was a retrospective chart review done in an eight-hundred patient opioid addiction treatment program in California from June 2008 until January 2013. The study followed sixty-two pregnant patients who were 83% white, 13% Hispanic, 2% African American, and 2% Asian. Of these sixty-two patients, 71% used primarily prescription opioids and 29% used mainly heroin. Some of these patients were already pregnant when they enrolled in treatment and some (32%) became pregnant after starting treatment with methadone. Sixty-six percent of these patients were smokers.

All the patients were moved to twice-daily dosing within several weeks of entry into treatment. Subsequent increases and further dividing of maternal dose was determined by maternal report of opioid withdrawal, and on methadone trough blood levels. All efforts were made to maintain maternal blood level in the “therapeutic range.” Most women dosed three or four times per day by the last trimester, and the average maternal dose at delivery was 152mg per day.
The highest dose in this study was seen in a pregnant patient who was a fast metabolizer of methadone. She required a total dose of 415mg, which was split into six doses. Interestingly, her infant did not need treatment for NAS.

The outcomes of the study were unusual in several ways.

Of the fourteen hundred urine drug screens collected on these pregnant patients, 88.4% were negative for illicit drugs. The mean gestational age was 38 weeks, and only 18% of the babies were born before 37 weeks gestation.

But here is the most noteworthy finding: only 29% of the babies had neonatal abstinence syndrome (NAS) that was severe enough to need treatment. As in other studies, this study showed no correlation between maternal dose and the incidence of NAS.

In the past, the incidence of neonatal withdrawal syndrome has been estimated at 60-80%, though the MOTHER study of 2010 (Jones et. al) found 50% of infants born to both moms on methadone and moms on buprenorphine had withdrawal that was severe enough to need treatment. (That study also found infants born to moms on buprenorphine stayed in the hospital half as long as babies born to moms on methadone, and also had much less severe NAS.)

In this present study, the babies conceived during methadone treatment were not significantly more likely to have NAS than the babies born to moms who conceived prior to entering medication-assisted treatment with methadone.

Male infants were a little more likely to need treatment for NAS than the females.

The authors concluded that divided methadone dosing and adequate methadone dosing during pregnancy increased maternal recovery and resulted in less stress on developing fetuses. The authors postulate there was less sensitization to repeated episodes of intrauterine withdrawal, which ultimately resulted in much lower rates of neonatal abstinence syndrome.

The authors also identified some limitations of their study, and recommended further investigation.

Over the last few years, doctors in North Carolina have been trying to do split dosing on pregnant women when possible. To do this, the woman must be stable enough to manage the second half of the dose, given as a take home. If there’s an addicted male partner at home, that second dose may fall into the wrong hands, and the pregnant patient can get shorted part of her dose. That’s not a good thing during pregnancy, so it’s all about balancing risks with benefits.

This is an intriguing study, but it’s probably too soon to change what we are doing in OTPs. I know I’d like to hear how ASAM experts interpret this information.

The information in this study was gleaned from a retrospective review of patients, which may not be as good a study as a prospective double-blind study, if such could be conducted.

I’m impressed with the 66% smoking rate. I estimate that around 95% of pregnant patients at the OTPs where I work are addicted to nicotine. But I live in a tobacco state, and the study, done in California, has fewer smokers. I think that might be a significant difference, because we know NAS is more like to occur in smokers. Did that play a role in the lower NAS incidence found in this study?

Did the authors of this study take any extra measures to ensure their pregnant patients were living in a safe environment, conducive to recovery? Are the authors sure their pregnant patients were able to consume all of their take home doses? Were any doses diverted, willingly or unwillingly, to other people? Sometimes female patients live with partners who are also addicted, and the patients may be tempted or coerced into giving a dose to a partner in opioid withdrawal. If this happened it could change conclusions of this study.

I suspect the average maternal dose in this study was higher than at most opioid treatment programs in my area. As the authors concluded, this likely improved the mothers’ health and outcomes. This study had a very low rate of positive drug screens, so these patients appear to have been doing exceptionally well in treatment. So is it possible that there could be less withdrawal in babies born to moms on higher doses? That seems counterintuitive, but the authors do suggest that could be why they had low NAS incidence.

The pregnant women in this study got more counseling and support from their OTP than may be provided in other OTPs. The patients in this study had a weekly meeting with a pregnancy counselor, weekly group meeting for education and support facilitated by the clinic physician, psychiatric assessment, and monthly supportive psychotherapy. They got weekly urine drug screens, so there was close accountability. They also had methadone trough blood levels drawn when needed.

The study presents intriguing data. We need more information, more studies to see if higher and divided methadone doses will provide better outcomes with less NAS, as was seen in this study.

Opioid Addiction in Pregnancy: More Information about the Use of Methadone Versus Buprenorphine

The MOTHER (Maternal Opioid Treatment: Human Experimental Research) trial of 2012 (Jones et al) gave us much-needed information about how buprenorphine compares to methadone when used to treat opioid-addicted pregnant women. This landmark study showed us buprenorphine can be just as effective as methadone. Babies born to moms on buprenorphine had the same incidence of opioid withdrawal (called neonatal abstinence syndrome, or NAS) at 50%, but the withdrawal was significantly less severe, the babies required about half the medication as the babies born to moms on methadone. Also, buprenorphine-exposed babies spent significantly less time in the hospital – about half as long as methadone-exposed infants.

Some doctors point out that more women on buprenorphine dropped out of that study than women on methadone, and say that proves buprenorphine is less effective. However, the majority of those women didn’t leave treatment; they just left the buprenorphine arm of the study.

This week I read another study, by Meyer et al, soon to be published in the Journal of Addiction Medicine. This study also looked at pregnant patients being treated for opioid addiction.

The authors of this new study pointed out that the MOTHER trial was a placebo- controlled, double- blind study comparing buprenorphine with methadone, but in real life, the decision to start an opioid-addicted pregnant woman on buprenorphine versus methadone is more complex, and determined by other factors. So the study by Meyer et al did a retrospective analysis. They looked at cases where the choice of buprenorphine versus methadone was made by the patient and physician, as happens in real life, then studied the outcomes. The authors of the new study believed findings will be more pertinent to what happens in everyday clinical practice.

In this retrospective cohort study, 609 pregnant patients were started on either buprenorphine (361) or methadone (248). This study took place over the years from 2000 to 2012 at a single site, University of Vermont.

The study collected various data about the newborns: their sex, estimate gestational age at delivery, birth weight, head circumference, length of stay in the hospital, whether the baby received breast milk, and if the child was sent home with the mother. The study also looked at if the newborn has NAS and if the baby needed medication, and length NAS treatment.

In the results, first-time mothers were significantly more likely to start buprenorphine than methadone. Mothers positive for Hepatitis C were more likely to be started on methadone. In both groups, more than 80% of the moms were smokers. About 30% of both groups had to have a C-section at delivery.

Both groups had similar prenatal care; more than 65% of the mother in both groups initiated care within the first trimester. However, women in the buprenorphine group were significantly more likely to get what the authors defined as “adequate” prenatal care. Women on buprenorphine were also more likely to already be in treatment when they became pregnant, compared to the women in the methadone group.

Nineteen women switched from buprenorphine to methadone, out of the three-hundred and sixty-one women who started on buprenorphine. Only five of those patients switched because buprenorphine was not strong enough for them, or other medication side effects. Most were switched to methadone because they needed more intensive monitoring at an opioid treatment program due to continued positive urine drug screens. Only three women out of the three-hundred and sixty-one started on buprenorphine dropped out and were lost from treatment.

No women were switched from methadone to buprenorphine, as one would expect. That’s because in order to switch from a full opioid, methadone, to a partial opioid, buprenorphine, the pregnant opioid addict would have to go into at least mild withdrawal, thus putting her at risk for adverse events. That’s not a risk most doctors are willing to consider.

Babies born to moms on buprenorphine, as compared to methadone, were significantly more likely to have longer gestational age. This is a good thing, because it means there were significantly fewer preterm deliveries on buprenorphine compared to methadone. The babies born to moms on buprenorphine were significantly more likely to have higher birth weights and bigger head circumference.

Just like what we saw in the MOTHER trial, this study also showed that the infants born to moms on buprenorphine required significantly less medication to treat neonatal abstinence syndrome. The buprenorphine-exposed babies required medication for a significantly shorter time than methadone-exposed newborns.

More than 95% of the infants were sent home in the care of the mother or family, which makes me think this study was done on women with fairly good stability at the time of delivery.

The authors of the study concluded that this evidence suggests that buprenorphine gives outcomes that are at least as good as with methadone.

I’d take that conclusion one step farther and say we now have several studies that show less neonatal withdrawal in babies exposed prenatally to buprenorphine compared to methadone. I have to ask myself: knowing what I do from these studies, which medication would I want to take during pregnancy? I’d prefer buprenorphine, and if it didn’t work for any reason, I’d switch to methadone.

I explain all of this to pregnant patients with opioid addiction upon admission, though I’m careful to also point out that methadone is still officially the gold standard in many places.

I think that will change soon. We are getting more information that shows outcomes equal to methadone with less severe neonatal withdrawal.

Opioid Use in Females of Child-bearing Age

Some obstetricians blame methadone clinics and buprenorphine providers for the high rate of opioid addiction they see in their pregnant population. OBs often seem angry that pregnant addicts are on methadone or buprenorphine.

This isn’t logical. Addiction medicine doctors are responding to the need for treatment in this population. We didn’t cause the opioid addiction problem; by the time pregnant opioid addicts see us, opioid addiction has been well-established. Addiction medicine doctors aren’t out combing the countryside, luring women of child-bearing years into our programs, trying to get them addicted to opioids. However, once opioid addiction is established, several decades of studies prove that medication-assisted treatment with methadone and buprenorphine produces the best results for both mother and child.

Now recent report from the Center for Disease Control (CDC) gives us a clue why so many pregnant women are addicted to opioids. The CDC’s January 23, 2015 issue of Morbidity and Mortality Weekly Report (better known as the MMWR) described a report on the frequency of opioid prescriptions in the U.S. for women of child-bearing years, aged 15 to 44:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6402a1.htm?s_cid=mm6402a1_w#tab

This data was collected each calendar year from 2008 through 2012 by a private firm with access to a massive database with information on over 5 million insured females aged 15 to 44.

The data revealed the percentage of women who filled at least one outpatient opioid prescription per year, and was further examined by region of the U.S., by type of insurance, by specific age groups, ethnicity, and by type of opioid prescribed. The data was collected not on pregnant women, but on women likely to become pregnant.

Averaging the four years of data, twenty-eight percent of the women with private insurance filled at least once opioid prescription per year, and thirty-nine percent of women with Medicaid filled at least one opioid prescription. On a slight positive note, the rates of opioid prescriptions hit a high mark in 2009, when twenty-nine percent of women with private insurance filled at least one opioid and a whopping forty-one percent of women covered by Medicaid filled at least one opioid prescription.

Granted, one prescription per year won’t cause an opioid addiction. But the study also looked at the average number of prescriptions per year in the women who did have at least one opioid prescription, and found women with private insurance averaged nearly three opioid prescriptions per year, and women with Medicaid averaged four and a half prescriptions per year. That’s not unexpected; Medicaid covered people tend to be sicker, with worse physical and mental health. Still, increased exposure to opioids correlates with increased rate of addiction to opioids.

In other words…U.S. doctors are prescribing a hell of a lot of opioids to women who can become pregnant.

Of the thirteen most commonly prescribed opioids to this age group, hydrocodone was the most commonly prescribed opioid for both privately insured and Medicaid insured women. Hydrocodone was prescribed to 17% of the privately insured women of child-bearing years, compared to 25% of Medicaid insured women. Next most common were codeine, oxycodone, tramadol, propoxyphene (taken off the market in 2010), hydromorphone (Dilaudid), meperidine (Demerol), morphine, and in ninth place was buprenorphine. Then came fentanyl, tapentadol, dihydrocodeine, and in last place was methadone, prescribed to one tenth of a percent of women of child-bearing years.

Keep in mind this last data point probably didn’t include methadone prescribed through opioid treatment programs, since Medicaid isn’t accepted as payment at many OTPs, and private insurance usually won’t pay for care at OTPs either. (In fact, this data likely underestimates the number of women prescribed opioids, since women with no insurance weren’t counted in the study.)

Prescribing rates were compared by the region of the U.S. The South has the highest rate of prescriptions for opioids in women of child-bearing years. Averaging all four years studied, the South prescribed opioids to 32% of women in this age group. The Northeast had the lowest rate, at 22%. The Northcentral and the West came in between, at 25% and 27% respectively.

This data mirrors what we’ve seen from other studies of regional prescribing rates for controlled substances (see my blog entry from August 25, 2014). I have my own opinions about why the rates are so different but for once I’m going to keep them to myself, lest I (again) anger my colleagues.

When separated by race, a much higher percentage of white women filled at least one opioid prescription per year, at 46%. This compares to 35% of black women and 34% of Hispanic women.

That’s dismaying, but is in line with previous studies that show black patients get prescribed opioid pain medications at a much lower rate than white patients with the same pain complaint when seen in emergency departments. One would assume this is due to racial bias, but there could be other reasons. For example, maybe whites demand opioid pain medication at a much higher rate than blacks. Obviously, we need more data to find out why we have such racial differences. In this case, being black could be a protective factor against developing iatrogenic (physician-caused) addiction, but is it at the cost of inadequate pain control? I don’t know.

When the data was examined by more narrowly defined age ranges, for women with private insurance, the highest percentage of prescribing was seen in the 30 to 34 age range, at 31%. For Medicaid-insured women, it was highest in the 40-44 age group, showing more than half of these women got at least one prescription for opioids per year.

This makes sense. The longer one is alive, the more medical issues one accumulates, perhaps needing pain control.

Here’s the bottom line: My interpretation of this study is that U.S. doctors, especially in the South, are prescribing too many pain pills to everyone, including to women who could become pregnant.

Around fifty percent of pregnancies in the U.S. are unplanned. With this many women getting pregnant without planning to do so, every doctor prescribing opioids needs to explain the risks of opioids during pregnancy. This includes opioid treatment program doctors like me.

Don’t blame the women. They don’t want to be addicted. In fact, no person with opioid addiction wanted or expected they would become addicted, even if they took their first opioid solely for the good feeling it produced. No one thinks they will become a hostage to opioids, especially if they are being prescribed these medications. How could patients know, when even doctors are poorly informed about the risk of developing opioid addiction?

Pregnant women with opioid addiction are not bad women, recklessly taking drugs and endangering their children. Most did not expect or plan to end up in this situation. These moms want to stop using, but the nature of opioid addiction shows that is a very difficult thing to do, and actually dangerous to try during pregnancy. Outcomes for both mom and baby have been proven to be best when the pregnant mom gets into treatment, on maintenance medications of methadone or buprenorphine.

Criminally Pregnant In Tennessee, Part II

Today my guest blogger Dr. Fedup weighs in on my last entry, “Criminally Pregnant,” with his own unique point of view. He gives counterpoints to my arguments, as he feels Tennessee’s law is a good idea. I’ll let him explain his reasoning. His political leanings are somewhat right of center, as you will read.

“I applaud Tennessee’s new law, which makes it a crime to expose a pre-born baby (I don’t believe in using that word fetus, since life begins at conception) to drugs. Too many babies are born with neonatal abstinence syndrome, so obviously Tennessee has grown too soft on crime for this to be happening.

“Bill number 1391, already passed by the state’s legislature, needs only the governor’s signature to become law. In short, this bill says a mother can be prosecuted for “an assaultive offense or homicide if she illegally takes a narcotic drug while pregnant and the child is born addicted, is harmed, or dies because of the drug.”

“Their governor, Bill Haslam, goofed last year when he passed that Safe Harbor Law, which eliminated criminal charges for pregnant women who went into treatment. This new law corrects and cancels that law. Some people have said that’s inconsistent, and not enough time passed since the Safe Harbor Law to see if it was going to work or not.

“I say it’s OK to be inconsistent so long as you are putting people in jail.

“There’s nothing in the new bill to prevent pregnant, opioid addicted women who are in methadone or buprenorphine programs from being prosecuted as well, though bill 1391 does say, “Illegally take a narcotic drug while pregnant.” Women who enter such treatments have already taken illegal narcotics while pregnant, or they wouldn’t need treatment.

“My only problem with the new bill, SB 1391, is that it doesn’t go far enough. We should put the drug addict babies in jail, too.

“Think about it. You know those little suckers enjoyed the drugs they were getting through the placenta, and they need to be punished for that. They’re born addicts. Start punishing them right out of the womb. That way, the state can teach them right from wrong as they grow up, right there in the prison system, like we do with all other inmates in Tennessee jails.

“Some people criticize my idea. Some people say we already put too many people in jail. But I say if U.S. history teaches us anything, it’s that taxpayers are always happy to spend more money on jails.

“We must be willing to incarcerate more people, because U.S. citizens are more evil and criminal than people in other parts of the world. They must be, because we put more people in jail per capita than anywhere else. Circular logic? I don’t care, as long as it puts bad people in jail.

“It was a happy day when the U.S. could finally brag that we incarcerate more people per capita, than even Russia or Rwanda. We’re Number One! We put 716 people out of 100,000 into jails or prisons, and Russia only puts 484 out of 100,000 in prisons. We’re beating them almost two to one! [1]

“Lots of bleeding heart liberals will complain about how Tennessee jails aren’t set up for infants. I say we can fix that. After all, aren’t play pens just jail cells, only prettier? These addict babies don’t deserve anything too pretty, and they’ll get used to the bars soon enough.

“No measure is too severe if it will fix the drug problem. My critics point to all the information collected since the 1950’s which indicates incarcerating addicts does nothing to help addiction rates. But I’m telling you that this new send-an-addict-baby-to-jail program will work.

“While we are on the topic of evil pregnant women who harm their babies, let’s discuss nicotine addiction. There’s more medical evidence to show tobacco smoking harms babies than there is to show cocaine harms babies. Let’s put all those mothers who smoke into jail, too, since they are intentionally harming their pre-borns.

“Then let’s take this train of thought to its logical conclusion. In the latest issue of the Journal of the American Medical Association, there was a great article about the harm maternal obesity does to the fetus. This article reviewed all of the studies of how obesity affects fetal death and infant death. The conclusion was, “Even modest increases in maternal BMI were associated with increased risk of fetal death, stillbirth, and neonatal, perinatal, and infant death.” [2]

“Sounds to me like it’s time to build jails for the fatties, too. Because the state of Tennessee believes that jail time corrects bad behavior.

1. http://en.wikipedia.org/wiki/List_of_countries_by_incarceration_rate
2. Aune, et al, “Maternal Body Mass Index and the Risk of Fetal Death, Stillbirth, and Infant Death: a Systematic Review and Meta-analysis,” JAMA, 2014; 311(15):1536-1546.

Pregnant Women Using Drugs

Pregnant addicts are the most stigmatized group in U.S. society. Even other drug addicts regard pregnant addicts with scorn. But the nature of addiction is the loss of control – pregnant addicts usually do want to stop using drugs, but have lost the power to do so without help. And even if they do seek help, pregnant women face special barriers to proper care. The stigmatization alone is enough to keep many women from getting help. They face overwhelming shame and blame from society and from their own families. Pregnant women don’t tell their obstetricians about their addiction, for fear they will be treated harshly by the professionals on whom they must depend to deliver medical care. I’ve already blogged about the atrocious misinformation some obstetricians accept as true about opioids addiction and treatment during pregnancy.  Female addicts, scared and ashamed to ask for help, try to hide their addiction as well as they can, and hope for the best.

If a pregnant addict does seek help, many treatment programs won’t accept her into treatment, because she is too high risk. Addiction treatment programs sometimes don’t want the liability of a pregnant addict.

At one of the opioid treatment programs where I used to work, a woman came for admission in her fifth month of pregnancy. I tried to be gentle as I asked her why she’d waiting so long to get help. She laughed without humor and told me she’d been turned away from three other treatment facilities. The first was an inpatient residential treatment program that turned her away because she was addicted to opioids. They told her if they took her into their treatment program, she would have to undergo withdrawal, because they did not “believe” in methadone or buprenorphine (Subutex). And if she went into withdrawal, she could miscarry.

They directed her to an inpatient detoxification program that also declined to admit her because they didn’t want her to miscarry while in their facility. They (correctly) referred her to an opioid treatment program. The first opioid treatment program offered only methadone, and since she preferred buprenorphine, they referred her to the clinic where I worked. This patient had (correctly) heard new studies showed less severe withdrawal in babies born to moms on buprenorphine (Subutex) compared to moms on methadone.  That clinic then referred her to our clinic, since we do use buprenorphine. All of this took a few weeks, delaying her entry to treatment. The treatment programs made the right decisions, but addiction treatment is so patchwork that it took time for her to ping-pong from place to place until she found the treatment she needed.

Pregnant women fear they will lose custody of their children if they admit to being addicted and ask for help. Sadly, in some counties in my state, their fear is well-grounded. Some women are told they will lose their children because they have enrolled in medication-assisted treatment with methadone or buprenorphine, even though it’s the treatment of choice for opioid-addicted pregnant women. In most cases, treatment center staff can act as advocates, and talk to social service workers who may not be well-informed about addiction treatment. Punishing a mom for getting help doesn’t help anyone. Word spreads in addict social networks, making other women less likely to get help for addiction.

Often, the pregnant addict’s husband or partner is also addicted. He may try to keep her away from drug addiction treatment, fearing loss of control over her, or he may feel like he’ll be asked to stop using drugs too. Even if she’s able to go to treatment, having a drug-using partner makes it more difficult to stop using herself.

Women, pregnant or not, tend to have childcare issues. If they want to get help, who will watch the children while they attend treatment?

Despite the difficulties faced by pregnant addicts, most want desperately to deliver a healthy baby. We know from several studies that harsh confrontation predicts addiction treatment failure in pregnant women. That is, if treatment facility personnel, obstetricians, nurses or any other member of the treatment team tries to blame and scare a pregnant addict into stopping drug use, it backfires. Pregnant women tend leave treatment when they are treated harshly, and have worse outcomes than women who stay in treatment.

I’ve written blogs about the negative attitudes some medical professionals have toward pregnant opioid addicts who come for treatment with buprenorphine (Subutex) or methadone. Thankfully, that’s not a universal attitude. Recently an obstetrician referred her patient to us, calling ahead to speed things along. I called her back after I saw the patient, and we had a cordial conversation which I appreciate all the more in view of negativity I’ve experienced in the past.

I thought again about the topic of opioid-addicted pregnant addicts because of an article in my most recent issue of Journal of Addiction Medicine. This article described the outcome of a study of opioid-addicted pregnant patients in rural Vermont. Since methadone and buprenorphine (Subutex) are the treatments of choice for these patients, the study looked to see if better access to these treatments improved outcomes. The results showed, not surprisingly, improved access to medication-assisted treatment for opioid addiction in pregnant addicts improved the health outcomes for both mothers and babies. Earlier research showed the same result, but this was a rural group, underrepresented in past studies.

Meyer, M, et. al, “Development of a Substance Abuse Program for Opioid-Dependent Nonurban Pregnant Women Improves Outcome,” Journal of Addiction Medicine, Vol. 6 (2) pp.124-130.

The MOTHER trial – New Information about Buprenorphine and Methadone in Pregnancy

 The long-awaited MOTHER trial is done, and the data just published. (1) MOTHER (Maternal Opioid Treatment: Human Experimental Research) was one of the first studies to follow pregnant opioid-addicts during pregnancy and up to 28 days after they delivered their babies.

 The purpose of the study was to compare the use of buprenorphine during pregnancy with the use of methadone. For the past forty years, methadone has been the treatment of choice for opioid-addicted pregnant women. This is because it prevents withdrawal in the mother and fetus. With short-acting, illicit opioids like heroin or OxyContin without the time release coating, the mother and baby get high peaks of opioid followed by periods of withdrawal.

 Healthy adults get very sick while in withdrawal, but they usually don’t die. However, the developing fetus can die during opioid withdrawal, and miscarriage or preterm labor are more likely to occur. Methadone, since it’s a long-acting opioid, can keep both mother and baby out of withdrawal for twenty-four hours, when properly dosed. Compared with opioid-addicted mothers left untreated, or treated with non-opioid means, methadone-maintained mothers have fewer complications, better prenatal care, and higher birth weight babies.

 Now for the bad part: about half of the infants born to moms maintained on methadone have opioid withdrawal symptoms. No one wants to see a newborn having symptoms of opioid withdrawal. And yet, it’s still better than the alternatives.

 But now, it appears that the use of buprenorphine during pregnancy gives as much benefit as methadone, but less severe withdrawal in the newborns. The percentage of babies with opioid withdrawal was similar in the methadone and buprenorphine groups, but the severity and duration of the babies’ withdrawal were markedly less.

 If a woman addicted to heroin or pain medications discovers she’s pregnant, her best choice is to get into treatment with buprenorphine. But if that’s not available, methadone is still better than other alternatives.

 1. “Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure,” by Hendree Jones, Karol Kaltenbach, et. al., New England Journal of Medicine, December 9, 2010, 363;24: pages 2320-2331.