Lorraine Milio

Fetal neurobehavioral effects of exposure to methadone or buprenorphine.

As part of a double-blind study of medication treatment for opioid dependence during pregnancy, 17 opioid-dependent pregnant women maintained on either buprenorphine or methadone underwent fetal monitoring at 24, 28, 32, and 36 weeks gestation. Maternal demographic information and infant outcomes did not significantly differ by medication group. Earlier in gestation (24 and 28 weeks), buprenorphine-exposed fetuses had higher levels of fetal heart rate variability, more accelerations in fetal heart rate and greater coupling between fetal heart rate and fetal movement than the methadone-exposed group (all ps < .05). Later in gestation (32 and 36 weeks), buprenorphine-exposed fetuses displayed less suppression of motor activity and longer duration of movements than the methadone-exposed group (all ps < .05). These results may have implications for the optimal treatment of the opioid-dependent pregnant woman.

Pregnancies exposed to methadone, methadone and other illicit substances, and poly-drugs without methadone: A comparison of fetal neurobehaviors and infant outcomes

BACKGROUND It is suspected that there is a continuum of impairment among prenatally drug-exposed infants, such that opioid and/or poly-drug exposure confers the highest risk for adverse neonatal outcomes than other classes of substances or single substance exposures. Suitable control groups are difficult to identify. This study compared fetal neurobehavioral development and infant outcomes in offspring of three groups of pregnant women in drug treatment. Exposure groups include: Methadone+other illicit substances (MM+Poly) and two groups currently abstinent for poly drug exposures: Methadone only (MM/A) and Non-Methadone (NM/A). METHODS Forty-nine women (19 MM+Poly, 18 MM/A, and 12 NM/A) underwent fetal monitoring at 36 weeks gestation at peak and trough levels of methadone (MM+Poly; MM/A) or at comparable morning and afternoon times (NM/A). Fetal heart rate (FHR), heart rate variability (FHRV) and motor activity (FM) data were collected. Infant measures included birth outcomes and Neonatal Abstinence Syndrome (NAS) assessment. RESULTS As compared to the NM/A group, cardiac measures were decreased in methadone-exposed fetuses at peak levels. FHR was significantly more suppressed in the MM+Poly group. FM was significantly lower in the MM/A vs. the NM/A group at both peak and trough, indicative of more persistent exposure effects. The MM+Poly group delivered 1 week earlier and required NAS pharmacological treatment twice as often as the MM/A group. CONCLUSIONS Results support the notion that poly-drug exposure may potentiate the effects of methadone on the fetus and infant and highlights the need for intensified treatment for methadone-maintained women who abuse other substances.

Association between depression and nonadherence to antiretroviral therapy in pregnant women with perinatally acquired HIV

Women with perinatally acquired HIV (PAH) face unique psychosocial challenges due to the presence of a lifelong chronic illness and often unstable living situations. With advances in HIV treatment, an increasing number of those with PAH are reaching childbearing age and becoming pregnant. Depression may be an important and common factor that complicates both treatment and pregnancy outcomes in this group. We conducted a retrospective cohort study in pregnant patients with PAH to determine if history of depression is associated with nonadherence to antiretroviral therapy (ART). We reviewed charts of women with PAH receiving prenatal care at a single institution from March 1995 to December 2012. ART nonadherence was measured by patient self-report of any missed doses in the third trimester. Demographic, obstetric, and HIV infection characteristics of patients with a history of depression (dPAH) were compared to patients without a history of depression. Nine pregnancies among 6 dPAH women and 14 pregnancies among 12 PAH women without a history of depression were identified. None of the dPAH women reported 100% adherence to ART in the third trimester while 57% of women without a history of depression reported strict adherence (p = 0.04). The mean HIV RNA level at delivery was higher among dPAH women (17,399 vs. 2966 copies/Ml; p = 0.03) and fewer reached an undetectable HIV RNA level (<400 copies/mL) at delivery (p = 0.03). We concluded that a history of depression may contribute to poor medication adherence and treatment outcomes among pregnant women with PAH. Focused attention on diagnosis and treatment of depression in the preconception period may lead to more optimal medication adherence.

Dosing adjustments in postpartum patients maintained on buprenorphine or methadone

Scant scientific attention has been given to examining the need for agonist medication dose changes in the postpartum period. Study objectives were: 1) to determine the need for medication dose adjustments in participants stabilized on buprenorphine or methadone 3 weeks before and 4 weeks after delivery, and 2) to evaluate the need for methadone dose adjustments during the first 7 days in participants transferred from buprenorphine to methadone at 5 weeks postpartum. Participants were opioid-dependent pregnant women who had completed a randomized, double-blind, double-dummy, flexible dosing comparison of buprenorphine to methadone. Participants received a stable dose of methadone (N = 10) or buprenorphine (N = 8) before and 4 weeks after delivery. Buprenorphine-maintained participants were transferred to methadone at 5 weeks postpartum. There were no significant differences predelivery and/or postdelivery between the buprenorphine and methadone conditions in the mean ratings of dose adequacy, “liking,” “hooked,” and “craving” of heroin or cocaine. Patient response to the conversion from buprenorphine to methadone seems variable. Buprenorphine-maintained participants required dose changes postpartum only after they transferred to methadone. Regardless of type of medication, postpartum patients should be monitored for signs of overmedication.

Maternal buprenorphine treatment and fetal neurobehavioral development

BACKGROUND: Gestational opioid use/misuse is escalating in the United States; however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders. OBJECTIVE: The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development. STUDY DESIGN: Forty‐nine buprenorphine‐maintained women who attended a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (ie, heart rate, motor activity, and their integration [fetal movement–fetal heart rate coupling]) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchic linear modeling. RESULTS: Fetal heart rate, heart rate variability, and heart rate accelerations were significantly reduced at peak vs trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks gestation and tended to intensify with advancing gestation. Fetal motor activity and fetal movement–fetal heart rate coupling were depressed from peak to trough at 36 weeks gestation. Polysubstance exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks gestation. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough. CONCLUSION: Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (≥13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine‐exposed infants, and recognition of the benefits of medication‐assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes.

Intrahepatic vein for fetal blood sampling: one center's experience

OBJECTIVE The objective of the study was to examine 1 centers experience with fetal blood sampling via the fetal intrahepatic vein (IHV) and cordocentesis. STUDY DESIGN Consecutive IHV and cordocentesis procedures between July 1987 and February 2006 were compared with respect to success rates, streaming at the sampling site, nonreassuring fetal heart rate (NRFHR), or need for urgent delivery post procedure. A subanalysis of cases with fetal thrombocytopenia was performed. Data were analyzed using Fishers exact and Student t tests. RESULTS Two hundred ten procedures (130 IHV samplings and 110 cordocenteses) were identified. Success rates were significantly higher with IHV sampling than with cordocentesis (84.6% vs 69.1%, P = .004). Streaming from the sampling site occurred after 0.79% of IHV procedures vs 30.8% of cordocenteses (P < .0001). There was no difference between IHV and cordocentesis in the incidence of NRFHR or need for immediate delivery. Twenty-five cases of fetal thrombocytopenia (20 sampled via IHV, 5 by cordocentesis) were identified. Streaming from the sampling site occurred in 0 of 20 IHV cases vs 2 of 5 cordocentesis cases (40%) (P = .03). CONCLUSION IHV has a significantly lower rate of streaming from the sampling site, compared with cordocentesis. Our data suggest that IHV sampling conveys a particular advantage when fetal thrombocytopenia is suspected.