The effect of gestational period on the association between maternal prenatal salivary cortisol and birth weight: A systematic review and meta-analysis

Background. Studies exploring the relations between maternal stress and fetal development show an association between increased maternal stress and adverse birth outcomes. A frequently proposed mechanism linking maternal prenatal stress and adverse birth outcomes is heightened concentrations of maternal cortisol. To date, studies exploring this association have reported conflicting results because of the diverse approaches taken to measuring cortisol and the wide variety of possible birth outcomes explored. To add clarity to the growing body of literature, this systematic review and meta-analysis reports empirical findings on the association between maternal prenatal salivary cortisol and newborn birth weight. Methods: Searches for relevant papers published up until November 2017 were run in MEDLINE, EMBASE, PsycINFO, and CINAHL. Non-English language papers were included and experts were contacted when necessary. We included data from human observational studies that were designed or had an underlying intention to measure maternal prenatal salivary cortisol and newborn birth weight. We only included data from measurements of salivary cortisol to prevent rendering of the review unsuitable for meta-analysis. Two independent reviewers assessed study eligibility and quality. For every maternal-fetal dyad, an area under the curve with respect to ground (AUCg) of maternal cortisol was calculated to determine a Pearson's correlation coefficient with a continuous measure of newborn birth weight. Correlation coefficients were then pooled across all stages of gestation. To examine if there are critical gestational periods in which the fetus may be more susceptible to elevated concentration of maternal salivary cortisol, a meta-analysis was performed on separate correlations calculated from gestational trimesters. Results: Nine studies with a total of 1606 maternal-fetal dyads demonstrated a negative correlation between pooled maternal salivary cortisol and birth weight (-0.24, 95% CI -0.28 to -0.20), but there was a high degree of heterogeneity between studies (I-2 = 88.9%). To investigate heterogeneity, subgroup analysis by trimester of the pooled correlation between salivary cortisol and birth weight was performed with the following correlations found: first trimester, -0.18 (95% CI -0.32 to -0.03, I-2 = 97.3%); second trimester, -0.20 (95% CI -0.28 to -0.12, I-2 = 98.3%); and third trimester, -0.30 (95% CI -0.33 to -0.26, I-2 = 85.4%). Discussion: A consistently negative association was observed between maternal cortisol and infant birth weight. The review highlights specific gaps in the literature on the relationship between maternal prenatal salivary cortisol and newborn birth weight. Although a significant negative correlation was found, substantial heterogeneity of effects and the likelihood of publication bias exist. The third trimester was revealed as a possible critical gestational period for heightened maternal cortisol concentration to affect birth weight. Challenges faced in this body of research and recommendations for future research are discussed.