Periconceptional Non-medical Maternal Determinants Influence the Tryptophan Metabolism: The Rotterdam Periconceptional Cohort (Predict Study)

Abstract

Background: The vital role of the maternal tryptophan (TRP) metabolism in maternal health and pregnancy is well established. However, non-medical maternal determinants influencing the TRP metabolism have been poorly investigated. We hypothesise that periconceptional maternal non-medical determinants alter the TRP metabolism, affecting both kynurenine (KP) and serotonin pathway (SP) metabolite concentrations. Therefore, we investigated the influence of non-medical maternal determinants on the TRP metabolism during the periconception period. Methods: About 1916 pregnancies were included from the Rotterdam Periconceptional Cohort between November 2010 and December 2020. Data on periconceptional non-medical maternal determinants were collected through questionnaires. Serum samples were collected at 8.5 (SD = 1.6) weeks of gestation and TRP, kynurenine (KYN), 5-hydroxytryptophan (5-HTP), 5-HT (5-hydroxytryptamine) and 5-hydroxyindole acetic acid (5-HIAA) were determined using validated liquid chromatography (tandem) mass spectrometry. Mixed models were used to determine associations between periconceptional non-medical maternal determinants and these metabolites. Results: In total 11 periconceptional non-medical maternal determinants were identified. Protein intake was positively associated with TRP ( β = .12, 95% CI = 0.07-0.17), while age, energy intake and body mass index (BMI) ( β = −.24, 95% CI = −0.37 to −0.10) were negatively associated with TRP. Age, BMI and total homocysteine were associated with higher KYN, whereas non-western geographical origin was associated with lower KYN ( β = −.09, 95% CI = −0.16 to −0.03). Protein intake and total homocysteine ( β = .07, 95% CI = 0.03-0.11) had a positive association with 5-HTP, while a negative association was found for energy intake. A non-western geographical origin and drug use were associated with higher 5-HT, and BMI with lower 5-HT ( β = −6.32, 95% CI = −10.26 to −2.38). Age was positively associated with 5-HIAA ( β = .92, 95% CI = 0.29-1.56), and BMI negatively. Conclusions: Periconceptional non-medical maternal determinants, including age, geographical origin, drug use, energy and protein intake, BMI and total homocysteine, influence KP and SP metabolite concentrations.