Background: During pregnancy, mother–child interactions trigger a variety of subtle changes in the maternal body, which may be reflected in the status of peripheral blood mononuclear cells (PBMCs). Although these cells are easy to access and monitor, a PBMC atlas for pregnant women has not yet been constructed.Methods: We applied single‐cell RNA sequencing (scRNA‐seq) to profile 198,356 PBMCs derived from 136 pregnant women (gestation weeks 6 to 40) and a control cohort. We also used scRNA‐seq data to establish a transcriptomic clock and thereby predicted the gestational age of normal pregnancy.Results: We identified reconfiguration of the peripheral immune cell phenotype during pregnancy, including interferon‐stimulated gene upregulation, activation of RNA splicing‐related pathways and immune activity of cell subpopulations. We also developed a cell‐type‐specific model to predict gestational age of normal pregnancy.Conclusions: We constructed a single‐cell atlas of PBMCs in pregnant women spanning the entire gestation period, which should help improve our understanding of PBMC composition turnover in pregnant women.

Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN⁺monocytes and IFN⁺non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

Hypothesising that maternal serum chemerin levels may be associated with preeclampsia, we investigated whether maternal serum chemerin levels differ between preeclamptic and healthy pregnant women. We also investigated the association of serum chemerin with metabolic parameters and the severity of the disease. This case-control study included 144 women (72 healthy and 72 preeclamptic women) in the third trimester of a singleton pregnancy. Clinical data and maternal serum were collected. The two groups were carefully matched for maternal age and gestational age. The maternal levels of serum chemerin were determined by enzyme-linked immunosorbent assay. The serum chemerin levels were found to be significantly increased in the women with preeclampsia (258.85±86.64 ng/mL) as compared with the healthy pregnant controls (210.80±47.34 ng/mL) (P<0.001). The serum chemerin concentrations in the severely preeclamptic women (289.6±74.43 ng/mL) were higher than those in the mildly preeclamptic women (228.1±87.99 ng/mL) (P<0.001). A stepwise regression analysis showed that the serum chemerin levels significantly and positively correlated with systolic blood pressure (P<0.001), free fatty acids (P<0.05) and serum creatinine (P<0.01). Chemerin levels are significantly increased in preeclampsia and independently associated with markers of dyslipidemia and with the severity of the preeclampsia. Further studies need to show the onset of the chemerin increase and its putative involvement in the pathophysiology of preeclampsia.

Purpose: To investigate and identify first-trimester fasting plasma glucose (FPG) is related to gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes in Shenzhen population. Methods: We used data of 48,444 pregnant women that had been retrospectively collected between 2017 and 2019. Logistic regression analysis was used to evaluated the associations between first-trimester FPG and GDM and adverse pregnancy outcomes, and used to construct a nomogram model for predicting the risk of GDM. The performance of the nomogram was evaluated by using ROC and calibration curves. Decision curve analysis (DCA) was used to determine the clinical usefulness of the first-trimester FPG by quantifying the net benefits at different threshold probabilities. Results: The mean first-trimester FPG was 4.62 ± 0.42 mmol/L. A total of 6998 (14.4%) pregnancies developed GDM.489(1.01%) pregnancies developed polyhydramnios, the prevalence rates of gestational hypertensive disorder (GHD), cesarean section, primary cesarean section, preterm delivery before 37 weeks (PD) and dystocia was 1130 (2.33%), 20,426 (42.16%), 7237 (14.94%), 2386 (4.93%), and 1865 (3.85%), respectively. 4233 (8.74%) of the newborns were LGA, and the number of macrosomia was 2272 (4.69%), LBW was 1701 (3.51%) and 5084 (10.49%) newborns had admission to the ICU, which all showed significances between GDM and non-GDM groups (all P < 0.05). The univariate analysis showed that first-trimester FPG was strongly associated with risks of outcomes including GDM, cesarean section, macrosomia, GHD, primary cesarean section, and LGA (all OR > 1, all P < 0.05), furthermore, the risks of GDM, primary cesarean section, and LGA was increasing with first-trimester FPG as early as it was at 4.19–4.63 mmol/L. The multivariable analysis showed that the risks of GDM (ORs for FPG 4.19–4.63, 4.63–5.11 and 5.11–7.0 mmol/L were 1.137, 1.592, and 4.031, respectively, all P < 0.05) increased as early as first-trimester FPG was at 4.19–4.63 mmol/L, and first-trimester FPG which was also associated with the risks of cesarean section, macrosomia and LGA (OR for FPG 5.11–7.0 mmol/L of cesarean section: 1.128; OR for FPG 5.11–7.0 mmol/L of macrosomia: 1.561; OR for FPG 4.63–5.11 and 5.11–7.0 mmol/L of LGA: 1.149 and 1.426, respectively, all P < 0.05) and with its increasing, the risks of LGA increased. Furthermore, the nomogram had a C-indices 0.771(95% CI: 0.763~0.779) and 0.770(95% CI:0.758~0.781) in training and testing validation respectively, which showed an acceptable consistency between the observed, validation and nomogram-predicted probabilities, the DAC curve analysis indicated that the nomogram had important clinical application value for GDM risk prediction. Conclusions: FPG in the first trimester was an independent risk factor for GDM which can be used as a screening test for identifying pregnancies at risk of GDM and adverse pregnancy outcomes.

Background: The association between maternal obesity and preterm birth remains controversial and inconclusive, and the effects of gestational diabetes mellitus (GDM) and preeclampsia (PE) on the relationship between obesity and preterm birth have not been studied. We aimed to clarify the relationship between prepregnancy body mass index (BMI) and the phenotypes of preterm birth and evaluate the mediation effects of GDM and PE on the relationship between prepregnancy BMI and preterm birth. Methods: We conducted a prospective cohort study of 43,056 women with live singleton births from 2017 through 2019. According to the WHO International Classification, BMI was classified as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5–25 kg/m2), overweight (BMI 25–30 kg/m2) and obese (BMI ≥30 kg/m2). Preterm birth was defined as gestational age less than 37 weeks (extremely, < 28 weeks; very, 28–31 weeks; and moderately, 32–36 weeks). The clinical phenotypes of preterm birth included spontaneous preterm birth (spontaneous preterm labor and premature rupture of the membranes) and medically indicated preterm birth. We further analyzed preterm births with GDM or PE. Multivariable logistic regression analysis and causal mediation analysis were performed. Results: Risks of extremely, very, and moderately preterm birth increased with BMI, and the highest risk was observed for obese women with extremely preterm birth (OR 3.43, 95% CI 1.07–10.97). Maternal obesity was significantly associated with spontaneous preterm labor (OR 1.98; 95% CI 1.13–3.47), premature rupture of the membranes (OR 2.04; 95% CI 1.08–3.86) and medically indicated preterm birth (OR 2.05; 95% CI 1.25–3.37). GDM and PE mediated 13.41 and 36.66% of the effect of obesity on preterm birth, respectively. GDM mediated 32.80% of the effect of obesity on spontaneous preterm labor and PE mediated 64.31% of the effect of obesity on medically indicated preterm birth. Conclusions: Maternal prepregnancy obesity was associated with all phenotypes of preterm birth, and the highest risks were extremely preterm birth and medically indicated preterm birth. GDM and PE partially mediated the association between obesity and preterm birth.