Background <p>In recent years, more and more evidence has confirmed the “Developmental Origins of Health and Disease (DOHaD)” hypothesis, which states that adverse environments in early life can increase the risk of long-term metabolic diseases such as obesity and diabetes. Gestational diabetes mellitus (GDM) and subclinical hypothyroidism (SCH) during pregnancy are the most common endocrine diseases, which directly interfere with the intrauterine development environment of the fetus and thus are ideal research entry points for validating and extending the DOHaD theory.</p> Objective <p>This study aims to deeply explore the early impact of maternal endocrine disorders during pregnancy (with a focus on GDM and SCH) on the healthy development of the fetus, using key indicators such as birth weight as measures of early health outcomes. The research objectives include: 1) To Identify potential biomarkers that can be used for early prediction of GDM and SCH; 2) To observe the extent to which GDM and SCH affect the pregnancy outcome.</p> Methods <p>This will be a prospective cohort study involving 300 pregnant women. In addition to collecting general demographic information and clinical data of pregnant women, we also collect peripheral blood, urine, and fecal samples from pregnant women during the early, middle, and late stages of pregnancy. We also collect placental and umbilical cord blood samples during delivery. We conduct multi-omics analysis on the samples to comprehensively screen for differentially expressed molecules related to gestational endocrine diseases (GDM and SCH) and adverse outcomes. The main evaluation indicators are the birth weight of the offspring, including low birth weight, macrosomia, small for gestational age, and large for gestational age. The secondary outcome indicators include the following: 1) neonatal-related outcomes that include intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), preterm birth, low Apgar score, admission to the neonatal intensive care unit (NICU); and 2) maternal pregnancy outcomes that include gestational hypertension, preeclampsia, eclampsia, anemia, spontaneous abortion, type of delivery (vaginal, assisted vaginal delivery or cesarean section) and other complications.</p> Conclusions <p>This study aims to establish a prospective Chinese pregnant cohort to investigate the effects of GDM and SCH on pregnancy outcomes. On this basis, this study will utilize multi-time-point collected biological samples and combine multi-omics technologies to identify high-risk phenotypic characteristics related to GDM and SCH, with the aim of achieving early identification, and hopefully, intervention in the future, thereby reducing adverse pregnancy outcomes and the risk of long-term chronic diseases in the offspring.</p> Trial registration <p>ClinicalTrials.gov ID: NCT05952739. Study Registration Dates: July 19, 2023.</p>