EXAMINING THE IMPACT OF PRECONCEPTION AND EARLY PREGNANCY SERUM LEVELS OF MATERNAL VITAMIN D ON CLINICAL MARKERS OF IMPLANTATION AND PREECLAMPSIA

Abstract

Vitamin D is a hormone rather than a vitamin, that is essential for overall health and wellbeing, including but not limited to the reproductive system. Although vitamin D is available through several sources, such as natural ultraviolet sunlight, food, and supplements, low circulating 25-hydroxyvitamin D (25(OH)D) levels of <30 ng/mL are common among pregnant women, with up to 69% of the US population suffering from the condition. Epidemiologic studies have suggested that low maternal serum 25(OH)D levels may be associated with adverse pregnancy outcomes, such as early pregnancy loss and preeclampsia, which may be initiated early in the pregnancy process during implantation and placentation. From a life course perspective, the periconception and early pregnancy period marks a critical time for establishing a healthy pregnancy. Implantation and placentation occur early in pregnancy and involve a complex process that relies on optimal endometrial receptivity and a host of hormonal and immunologic signaling events. Disruptions to this process may be indicated by early clinical markers of pregnancy complications (e.g., vaginal bleeding or subchorionic hemorrhage) and associated with later adverse outcomes (e.g., preeclampsia). In contrast, higher Human Chorionic Gonadotropin (hCG) levels, which have been linked to nausea and vomiting, may be markers of robust implantation and placentation. Therefore, I sought to investigate the preconception and early gestation maternal serum 25(OH)D levels on: (i) vaginal bleeding and subchorionic hemorrhage; (ii) nausea and vomiting; (iii) preeclampsia. In Aim 1, an analysis of medical record documentation of vaginal bleeding and subchorionic hemorrhage found that women who were persistently deficient/insufficient in maternal serum 25(OH)D at both preconception and 8-week gestation had 2.18 times higher (95% CI: 1.13, 4.20) odds of having subchorionic hemorrhage compared to women who remained sufficient across both time periods, even after adjustment for potential confounders. Additionally, an analysis of daily diaries showed women with deficient 25(OH)D levels had a higher odds (OR: 3.02, 95% CI: 1.13, 8.13) of moderate/heavy bleeding versus none compared to women with sufficient 25(OH)D levels based on self-reported daily diaries on vaginal bleeding at the start of pregnancy. In Aim 2, women with persistently deficient 25(OH)D levels at both preconception and early gestation had lower odds (OR: 0.34, 95% CI: 0.20, 0.60) of experiencing nausea and vomiting based on medical records. In comparison, women who increased their 25(OH)D levels early in pregnancy (i.e., were deficient/insufficient at preconception then became sufficient at 8-week gestation) had 1.71 (95% CI: 1.12, 2.61) times higher odds of nausea and vomiting compared to those who were persistently sufficient across both time periods. Based on self-reported nausea and vomiting symptoms from daily diaries, deficient 25(O)D was associated with lower odds (OR 0.65; 95% CI 0.40, 1.06) of both nausea and vomiting when comparing to sufficient 25(OH)D levels. In Aim 3, women who had deficient 25(OH)D at preconception had an increased risk (RR: 1.45, 95% CI: 0.64, 3.29) of preeclampsia (as identified from medical records), although results were insignificant. Linear spline models demonstrated that the risk of preeclampsia declined with each 1 ng/mL increase of 25(OH)D levels up to 40-45 ng/mL (RR: 0.97, 95% CI: (0.93, 1.00), but that levels beyond this threshold show an increase in the risk of preeclampsia for each 1 ng/mL increase in 25(OH)D (RR: 1.03; 95% CI: 1.00, 1.06). This research highlights the importance of exploring the maternal serum levels of 25(OH)D at both preconception and early gestation and how it may affect adverse pregnancy outcomes, such as vaginal bleeding, subchorionic hemorrhage, preeclampsia, and pregnancy outcomes that signify a robust implantation response, such as nausea and or vomiting. It further underscores the importance of assessing maternal serum 25(OH)D levels prior to critical time of implantation and placentation and potential biologic mechanisms that may lead to adverse pregnancy outcomes. Supporting healthy implantation and placentation is of utmost importance as this may guide the remainder of the health of the pregnancy, and any disruption to this process may increase the mother and infant’s risk of maternal morbidity and mortality (e.g., preeclampsia, vaginal bleeding, subchorionic hemorrhage). Future studies are needed with more diverse, larger sample sizes, and both paternal and maternal nutrition to further assess preconception nutritional risk factors on adverse and robust pregnancy outcomes. Accordingly, this research is vital as it may aid in identifying early factors that may reduce adverse maternal and infant health outcomes.