Materials and Methods

This study was a retrospective analysis of data collected prospectively during ongoing prenatal care of opiate addicted pregnant women managed by the Maternal-Fetal Medicine Department at the University of Tennessee Medical Center (Knoxville, TN). Data were evaluated for fetal complications of intrauterine fetal demise, fetal distress, and preterm labor leading to delivery in pregnancies that underwent detoxification of opiate addiction during pregnancy.

Four different methods occurred but were not specifically compared with each other because there was no randomization and the treatment methods varied because of circumstances that could not be controlled. Group 1 consisted of incarcerated patients. These pregnant women underwent acute detoxification involuntarily because the jail program in east Tennessee has no ability to provide opiates to prevent or perform an opiate-assisted medical withdrawal. The physician who oversees the incarcerated patients can treat symptoms of withdrawal with antiemetic agents, antidiarrheal drugs, and clonidine, but no opiates are provided. Furthermore, fetal monitoring is also not available and was not performed during the detoxification process, although fetal heart tones were intermittently auscultated. These patients did have excellent prenatal follow-up (while incarcerated) because the jail system assured the scheduling of office visits and provided guaranteed transportation to and from appointments. However, if the patient was released from incarceration prior to delivery, responsibility for prenatal care visits would fall back on the patient and missed appointments would occur in some cases, but all patients were still delivered by the maternal-fetal medicine group.

The second and third groups went through an inpatient drug detoxification program that uses buprenorphine and fully detoxifies the patient in 5–8 days, treating other physical symptoms as they develop. The majority of these patients (>90%) were addicted to prescription opiates (such as oxycodone, oxymorphone, and hydrocodone) obtained through diversion. When admitted, they would be treated with buprenorphine and then rapidly tapered. Again, fetal monitoring was not performed during the process, but heart tones were intermittently auscultated. Once fully detoxified, which occurred in every case, an attempt is made to place the patient in an intense behavioral health program that involves either a home that allows for the patient to stay (with her children) that is monitored daily or a daily 8 hour program that the patient participates in Monday through Friday. These inpatient detoxified patients that have intense behavioral health follow-up make up group 2. Unfortunately, the available spaces for these intense behavioral health programs are greatly limited, and many patients cannot be accommodated. Thus, inpatient detoxification patients that are not followed with intense outpatient follow-up management make up group 3.

The fourth group involves the outpatient slow buprenorphine detoxification program, which is performed by a few clinics in the East Tennessee area that will stabilize the patient on a maintenance dose and then slowly taper them down to zero over 8 to 16 weeks depending on the motivation of the patient and the gestational age of the pregnancy. Once fully detoxified, these patients are maintained in continued behavioral health follow-up.

Because the study purpose was to evaluate the safety of opiate detoxification during pregnancy, only patients who were fully detoxified were included. All of the patients in groups 1, 2, and 3 were fully detoxified based on the process of their grouping. Some of the patients who were managed in the outpatient buprenorphine group were not successful at becoming fully detoxified, and these unsuccessful patients are part of another ongoing study.

To make the assessments equal between the groups, only those who completely detoxified in this outpatient group were included and make up group 4.

No other exclusion criteria were included. For definition purposes, the trimester for when detoxification occurred was defined based on when the process was fully completed and was easily demarcated for groups 1, 2, and 3 because of the short duration. For group 4, because the detoxification process occurred over a period of weeks, some patients may have begun detoxification in an earlier trimester.

For the secondary study objective, the incidence of delivering a neonate that was treated for neonatal abstinence syndrome was also collected for each method to determine whether there was any difference in effectiveness at minimizing this condition for the newborn. Relapse rates for all of the study patients were analyzed and relapse was defined as a positive drug screen on admission, an admission by the patient at the time of delivery that she had relapsed, or a positive neonatal meconium test.

Neonatal abstinence syndrome is a reportable condition to the State of Tennessee Health Department. Every newborn at our medical center that is delivered of a mother who is or was taking opiates during the pregnancy, either by history or by positive drug screen on admission, is followed up by the neonatal intensive care physicians for 3–5 days. Finnegan scores are performed and if a score of ≥10 is obtained twice, 3 hours apart, or ≥12 once, then the diagnosis is made and the newborn is further treated.

Demographics of age, ethnicity, gravidity and parity, gestational age at the time of full detoxification, gestational age at delivery, and newborn outcome with Apgar scores were collected. Admission to the neonatal intensive care unit and development of neonatal abstinence syndrome were also collected.

This study was reviewed and approved by the Institutional Review Board of the University of Tennessee Medical Center (Knoxville). Study patients were obtained during a 5.5 year period from 2010 to 2015. Comparisons were conducted by χ ² , Fisher exact, and Student t test where applicable, and P < .05 was considered significant.

Results

A total of 301 opiate-addicted pregnant patients were fully detoxified during pregnancy with no adverse fetal outcomes related to detoxification identified. Demographics are seen in Table 1 . There were no differences in mean maternal age, maternal age range, or the number of patients under the age of 30 years. However, as depicted, 3 of 4 patients were younger than 30 years of age, consistent with what has previously been reported.

The majority of patients in each group were multiparous, with a 78% rate for the entire study population. Group 1 had a statistically higher number of multiparous patients when compared with groups 2 and 3 at P = .008. Additionally, 88% of the entire study population was white. There were a statistically higher number of African-Americans in group 1 compared with the other groups ( P < .01).

Table 1 also depicts the gestational age at the time of detoxification and the admission rate to the neonatal intensive care unit. Of the 301 patients, there were 28 detoxified in the first trimester from 5 through 13 weeks’ gestation. Two intrauterine fetal demises occurred in this group and both were patients acutely detoxified. One involved a patient who was acutely detoxified at 10 weeks’ gestation but had an intrauterine fetal demise at 18 weeks’ gestation with a placental abruption. She was still incarcerated and her drug screen at the time of the loss was negative. The second was also acutely detoxified at 12 weeks’ gestation and was found to have an intrauterine fetal demise at 34 weeks’ gestation of a fetus with hydropic changes. Autopsy was declined and her drug screen and testing were all negative at the time of diagnosis as well.

There were 148 detoxified in the second trimester from 14 weeks through 27 weeks, and 125 detoxified in the third trimester from 28 weeks’ gestation and greater with no episodes of intrauterine fetal demise. There were no cases of preterm premature rupture of membranes or preterm delivery that occurred during the process of detoxification.

Regarding the rate of treatment for neonatal abstinence syndrome (seen at the bottom of the Table 1 ), 94 patients (31%) overall delivered a neonate that was treated for neonatal abstinence syndrome. Of the 301 patients, 108 were acutely detoxified while incarcerated (group 1 patients), and 20 cases of neonatal abstinence syndrome occurred following delivery, for a rate of 18.5%.

There were 100 patients who were detoxified as an inpatient with 23 who were placed in long-term follow-up behavioral health programs following the detoxification (group 2 patients), and 4 newborns had neonatal abstinence syndrome after delivery for a rate of 17.4%. The remaining 77, who were without intense outpatient follow-up management (group 3 patients), delivered 54 neonates that were treated for neonatal abstinence syndrome for a rate of 70.1%. Finally, there were 93 who were fully detoxified with buprenorphine as an outpatient (group 4 patients) and 16 newborns were diagnosed with neonatal abstinence syndrome for a rate of 17.2%.

A positive drug screen on admission, an admission by the patient at the time of delivery that she had relapsed, or a positive neonatal meconium test was found in all of the neonates treated for neonatal abstinence syndrome. Table 1 depicts the numbers of women in each group who relapsed back to taking opiates as defined. As shown, relapse is higher than the rate of treatment for neonatal abstinence syndrome for each group because there were some that relapsed as defined, but the neonates did not experience neonatal abstinence syndrome.

Excluding group 1 patients who were acutely detoxified following incarceration, group 2 and group 4 patients combined represent those who were fully detoxified and remained in long-term behavioral health settings. The rate of neonatal abstinence syndrome in this combination was 20 in 116, or 17.2%. If this is compared with group 3 (those detoxified and managed without intense outpatient follow-up management) with a rate of 54 in 77, or 70.1%, the difference is highly significant at P < .0001.

The overall delivery rate prior to 37 weeks’ gestation (53 patients) is somewhat high at 17.6%, but 28 of these (53%) were inductions of labor for a diagnosis of severe intrauterine growth restriction. Interestingly, at the time of delivery, the fetal weight was <5% in only 16 of the 28 (57%). The preterm delivery rates were no different based on when detoxification occurred. Likewise, 40% of the newborns were admitted to the neonatal intensive care unit, but this includes the 31% treated for neonatal abstinence syndrome. The remaining 9% primarily included admissions for prematurity or for extended observation for signs of neonatal abstinence syndrome.