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

Abstract

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.

Figure 1. Fetal data collected at Time 1 (trough methadone) and Time 2 (peak methadone) in the two Methadone-exposed groups and at comparable morning and afternoon times in the in Non-methadone group. Notations refer to significance of differences in slope

a) The Methadone+Poly-drug group showed significantly greater suppression in fetal heart rate (bpm) from Time 1 to Time 2 as compared to both the Non-Methadone and the Methadone only groups. b) The Methadone+Poly-drug group (MM+Poly) showed significantly greater suppression in fetal heart rate variability from Time 1 to Time 2 as compared to the Non-Methadone group (NM/A) and a trend level difference as compared to the Methadone only (MM/A) group in heart rate variability from Time 1 to Time 2. c) Although there were significant differences at each recording between the Non-methadone and Methadone+Poly drug groups (see Table 3), in fetal motor activity (i.e., the proportion of time engaged in motor activity during the 1-hour recording), slopes did not differ over time.

Figure 1. Fetal data collected at Time 1 (trough methadone) and Time 2 (peak methadone) in the two Methadone-exposed groups and at comparable morning and afternoon times in the in Non-methadone group. Notations refer to significance of differences in slope

a) The Methadone+Poly-drug group showed significantly greater suppression in fetal heart rate (bpm) from Time 1 to Time 2 as compared to both the Non-Methadone and the Methadone only groups. b) The Methadone+Poly-drug group (MM+Poly) showed significantly greater suppression in fetal heart rate variability from Time 1 to Time 2 as compared to the Non-Methadone group (NM/A) and a trend level difference as compared to the Methadone only (MM/A) group in heart rate variability from Time 1 to Time 2. c) Although there were significant differences at each recording between the Non-methadone and Methadone+Poly drug groups (see Table 3), in fetal motor activity (i.e., the proportion of time engaged in motor activity during the 1-hour recording), slopes did not differ over time.

Figure 1. Fetal data collected at Time 1 (trough methadone) and Time 2 (peak methadone) in the two Methadone-exposed groups and at comparable morning and afternoon times in the in Non-methadone group. Notations refer to significance of differences in slope

a) The Methadone+Poly-drug group showed significantly greater suppression in fetal heart rate (bpm) from Time 1 to Time 2 as compared to both the Non-Methadone and the Methadone only groups. b) The Methadone+Poly-drug group (MM+Poly) showed significantly greater suppression in fetal heart rate variability from Time 1 to Time 2 as compared to the Non-Methadone group (NM/A) and a trend level difference as compared to the Methadone only (MM/A) group in heart rate variability from Time 1 to Time 2. c) Although there were significant differences at each recording between the Non-methadone and Methadone+Poly drug groups (see Table 3), in fetal motor activity (i.e., the proportion of time engaged in motor activity during the 1-hour recording), slopes did not differ over time.