Perinatal & Pediatric
Pre-Pregnancy and First-Trimester Hair Cortisol Predicts Preterm Birth in Pregnant Women in Perú: A Causal Inference Model Richard Künzel* Richard G. Künzel Yinxian Chen Sixto E. Sanchez Marta B. Rondon Nelida I. Pinto Elena Sanchez Clemens Kirschbaum Linda Valeri Karestan C. Koenen Bizu Gelaye
Approximately 87% of pregnant women in Perú have experienced at least one traumatic life event. Traumatic life events and other forms of psychological stress have frequently been associated with preterm birth (PTB), but the underlying biological mechanisms remain unclear. A promising biological mechanism is the hypothalamic-pituitary-adrenal (HPA) axis, a system involved in both, stress, and pregnancy regulation.
Investigating N = 1,808 pregnant Peruvian women, we examined the effect of pre-pregnancy and first-trimester hair cortisol (HCC) and hair cortisone concentrations (HCNC), which are novel chronic biomarkers of the HPA axis, on the risk of PTB. Using propensity scores to create stabilized inverse probability weights, we construct marginal structural models for causal association estimation.
While both independent one-log-unit increases from the population-mean pre-pregnancy HCC (Risk Ratio (RR) = 0.87; 95%CI: 0.64, 1.19) and HCNC (RR = 0.82; 95%CI: 0.59, 1.14) were associated with decreased risk of PTB, first-trimester HCC (RR = 1.50; 95%CI: 1.13, 2.01) and HCNC (RR = 1.41; 95%CI: 1.06, 1.87) were linked to increased PTB risk. Interestingly, if HCNC had been elevated in both, pre-pregnancy and first trimester, the increased PTB risk due to the elevated first-trimester HCNC would have been attenuated (RR = 1.07; 95%CI: 0.75, 1.52) compared to a HCNC increase only in the first trimester (RRpre-pregnancy*first trimester = 0.76, 95%CI: 0.63, 0.91). Furthermore, the HCNC/HCC ratio, which is thought to represent 11β-HSD-2 activity, was negatively associated to PTB in all occurrences.
Our findings show that corticosteroid levels before and in early pregnancy are linked to PTB risk. Moreover, our results implicate that the temporal trajectory of chronic corticosteroid concentrations, which may be influenced by previous experiences of traumatic life events or psychological distress, is crucial for PTB prediction.