Increased risk of preterm delivery with high cortisol during pregnancy is modified by fetal sex: A cohort study

Authors: OAKS, BRIETTA - University Of Rhode Island; ADU-AFARWUAH, SETH - University Of Ghana; ASHORN, PER - University Of Tampere; LARTY, ANNA - University Of Ghana; Laugero, Kevin; OKRONIPA, HARRLET - Oklahoma State University; STEWART, CHRISTINE - University Of California, Davis; DEWEY, KATHRYN - University Of California, Davis

Submitted to: BMC Pregnancy & Childbirth
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2022
Publication Date: 9/23/2022
Citation: Oaks, B., Adu-Afarwuah, S., Ashorn, P., Larty, A., Laugero, K.D., Okronipa, H., Stewart, C., Dewey, K. 2022. Increased risk of preterm delivery with high cortisol during pregnancy is modified by fetal sex: A cohort study. BMC Pregnancy & Childbirth. 22. Article 727. https://doi.org/10.1186/s12884-022-05061-8.
DOI: https://doi.org/10.1186/s12884-022-05061-8

Interpretive Summary: Previous research has indicated a link between maternal cortisol and preterm birth. However, it is undetermined whether elevated cortisol during pregnancy increases risk for preterm birth in women living in underdeveloped, lower-income countries, such as Ghana. Compared to the global average, Ghana has a higher rate of preterm birth, but the reasons are unclear. Therefore, this research study of 783 pregnant Ghanian women, conducted in Ghana, examined whether maternal cortisol during pregnancy associated with preterm birth. Interestingly, researchers found that elevated levels of circulating cortisol increased risk of preterm birth by three times, but only in women carrying males. The researchers did not see an association between cortisol and preterm birth in women carrying females. Results imply that higher maternal cortisol may explain significantly shorter pregnancies and a higher rate of preterm birth in women pregnant with males. Further research is warranted to further understand the biological mechanisms for the cortisol-preterm birth relationship, and why this relationship does not appear to explain preterm birth in women carrying female fetuses.

Technical Abstract: Background: Previous studies show an association between cortisol and preterm birth. However, most studies have been conducted in high-income countries. It is unknown whether cortisol is a risk factor for preterm birth in Ghana, which has a higher rate of preterm birth than the global average. Our objective was to determine whether maternal cortisol during pregnancy was associated with pregnancy duration and preterm birth in Ghana. Methods: We conducted a cohort study of 783 pregnant women in Ghana. We measured salivary cortisol at baseline (mean 16 wk gestation), 28 wk, and 36 wk gestation. Pregnancy duration was determined by ultrasound. Data was analyzed using linear regression models and poisson regression models were used to determine risk of preterm birth. Results: Mean pregnancy duration was 39.4 ± 1.8 wk. Mean maternal cortisol increased throughout pregnancy, from 4.9 ± 2.7 nmol/L at baseline to 6.4 ± 3.2 nmol/L at 28 wk, and 7.9 ± 3.0 nmol/L at 36 wk gestation. In adjusted analyses, higher cortisol concentrations at baseline (ß = -0.39, p = .002) and 28 wk (ß = -0.49, p = .001), but not 36 wk (ß = -0.23, p = .084) were associated with a shorter pregnancy duration. Women with high cortisol at baseline (>6.3 nmol/L) had an increased risk of preterm birth (RR (95% CI): 1.96 (1.13, 3.40)). There was not a significant association between high cortisol at 28 wk and preterm birth. There was a significant interaction with fetal sex (p = 0.037). Among women carrying male fetuses, high cortisol at baseline increased the risk of preterm birth by threefold (RR (95% CI): 3.18 (1.51, 6.71)) while among women carrying female fetuses there was no association between high cortisol and preterm birth. Conclusion: Higher maternal cortisol is associated with a shorter pregnancy duration and an increased risk of preterm birth. Subgroup analysis by fetal sex revealed this association is primarily driven by women carrying male fetuses. Future studies of cortisol and preterm birth should include consideration of fetal sex as a potential effect moderator.