Mid-Gestational Enlargement of Fetal Thalami in Women Exposed to Methadone during Pregnancy.

Meredith Schulson,Tracey Bjã¶Rkman,Michael Peek,Ann Quinton,Ron Benzie,Ralph Nanan,Kristy P Mann,Anthony Liu

doi:10.3389/fsurg.2014.00028

Abstract

Methadone maintenance therapy is the standard of care in many countries for opioid-dependent women who become pregnant. Despite recent evidence showing significant neurodevelopmental changes in children and adults exposed to both licit and illicit substances in utero, data on the effects of opioids in particular remains scarce. The purpose of this study was to examine the effects of opiate use, in particular methadone, on various fetal cortical and biometric growth parameters in utero using ultrasound measurements done at 18–22 weeks gestation. Head circumference (HC), bi-parietal diameter, lateral ventricle diameter, transcerebellar diameter, thalamic diameter, cisterna magna diameter, and femur length were compared between fetuses born to methadone-maintained mothers and non-substance using controls. A significantly larger thalamic diameter (0.05 cm, p = 0.01) was observed in the opiate-exposed group. Thalamic diameter/HC ratio was also significantly raised (0.03 mm, p = 0.01). We hypothesize here that the increase in thalamic diameter in opiate-exposed fetuses could potentially be explained by regional differences in opioid and serotonin receptor densities, an alteration in monoamine neurotransmitter systems, and an enhancement of the normal growth increase that occurs in the thalamus during mid-gestation.

Highlights

Methadone maintenance therapy is the standard of care in many countries for opioid-dependent women who become pregnant [1, 2]
Forty-two fetuses with fetal anomaly scans (FAS) between 18 and 22 weeks were identified from our cohort of methadone-maintained mothers
The pre-natal increase in thalamic size, we have demonstrated may potentially be explained by normal developmental patterns of the thalamus and by regional differences in opiate-receptor density and monoamine neurotransmitter systems within the brain

Summary

Introduction

Methadone maintenance therapy is the standard of care in many countries for opioid-dependent women who become pregnant [1, 2]. There are many benefits to the use of methadone during pregnancy, it readily crosses the placenta, enters the bloodstream of the fetus and imposes potential risks [3, 4]. The main documented adverse outcome of methadone use during pregnancy is the development of neonatal abstinence syndrome (NAS), with withdrawal being reported in more than 50% of infants born to methadone-maintained mothers [5]. Recent evidence shows that exposure to both licit and illicit substances causes significant structural brain changes in children, adolescents, and adults, which leads to the hypothesis that there may be significant effects on the brains of fetuses as well [9,10,11]. These changes are diverse in terms of regions of the brain affected, and in terms of the specific effects themselves, and occur on a cellular, macroscopic structural, and functional/behavioral level [9,10,11,12,13]

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