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

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.

Clinical and basic research investigations into the long‐term effects of prenatal opioid exposure on brain development

“…Other structural deficits associated with POE in humans are not outwardly apparent and can only be observed through medical imaging (Table 1). As early as 18-22 weeks of gestation, ultrasound studies have found that fetuses whose mothers were undergoing methadone maintenance therapy had significantly larger thalamic diameter-to-head circumference ratios compared to a control group (0.90 ± 0.1 vs. 0.87 ± 0.1 mm; p = 0.01; Schulson et al, 2014). One ultrasound study observed abnormally small, slit-like ventricles in 13 out of 16 NAS-affected 1-month-old infants compared to 0 out of 11 control infants (Pasto et al, 1985).…”

Normative ultrasound data of the fetal transverse thalamic diameter derived from 18 to 22 weeks of gestation in routine second‐trimester morphology examinations

“…Therefore, size of the thalamus forms an important anatomical basis ‘for the impaired cognitive performances’ in ADHD . The growth of the fetal thalamus is affected in women who are opioid dependent and smoke during pregnancy . Further, increased thalamic volume, measured with ultrasound, has been associated with growth‐restricted fetuses who have haemodynamic flow redistribution to the brain as a protective measure associated with hypoxia and an increased risk of neurodevelopmental delay …”

“…8 The growth of the fetal thalamus is affected in women who are opioid dependent and smoke during pregnancy. 9 Further, increased thalamic volume, measured with ultrasound, has been associated with growth-restricted fetuses who have haemodynamic flow redistribution to the brain as a protective measure associated with hypoxia and an increased risk of neurodevelopmental delay. 10 Structural anomalies of the thalamus can be identified in the fetus with midline malformations such as holoprosencephaly.…”

An Automated Framework for Large Scale Retrospective Analysis of Ultrasound Images

“…However, much more information is embedded in the routinely acquired US images than just the characteristics of the standard set of anatomical structures, and this additional information are currently unused. This information can potentially be used to determine the influence of antenatal factors on fetal development [5], e.g., thalamic size as measured on the US images may be associated with maternal methadone usage and hence may influence neuro-developmental outcomes [6]. This approach requires the understanding the relationship between environmental factors and health outcomes with the fetal growth and anatomical parameters encoded within the US image.…”