Neurosteroid involvement in threatened preterm labour

Abstract

Introduction: The neurosteroid allopregnanolone modulates oxytocin expression in the brain, and its effects arise from its action on the GABA_A receptor. Whether neurosteroid levels and the function of the GABA_A receptor are involved in the risk of preterm labour in pregnant women is unknown.

Methods: Pregnant women with (n = 16) or without (n = 20) threatened preterm labour (TPL) in gestational week 33 + 6 days to 37 + 0 days were studied prospectively with procedures including foetal heart rate monitoring, vaginal examination, ultrasound examination and blood tests to determine allopregnanolone, progesterone and oxytocin levels. The GABA_A receptor function in both groups was measured with a saccadic eye velocity test (SEVT).

Results: Plasma oxytocin levels were higher in the TPL group than in the control group (41.5 vs. 37.0 pmol/L, respectively, p = .021). Although the allopregnanolone and progesterone levels in both groups did not differ, there was a negative association between blood oxytocin and allopregnanolone (as predictor) levels in the TPL group (B: -3.2, 95% confidence interval (CI): -5.5 to -0.9, p = .012). As a predictor of TPL, progesterone was associated with cervix maturity (odds ratio: 1.02, 95% CI: 1.00-1.04, p = .038). SEVT showed that the women in both groups had similar GABA_A receptor functions. In both groups, body mass index correlated with peak saccadic eye velocity (r = .34, p = .044) and negatively with allopregnanolone (r = -.41, p = .013).

Conclusions: Neurosteroid levels were unchanged in the peripheral blood of women with TPL, despite the increase in available oxytocin. Although the function of the GABA_A receptor was unchanged in women with TPL, to ensure reliable results, saccadic eye velocity should be investigated during a challenge test with a GABA_A receptor agonist.

Keywords: GABAA receptor; allopregnanolone; oxytocin; progesterone; saccadic eye velocity.