Deep metagenomic characterization of the gut virome in pregnant women with preeclampsia.

Preeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

Deep metagenomic characterization of gut microbial community and function in preeclampsia.

Preeclampsia (PE) is a pregnancy complication characterized by severe hypertension and multiple organ damage. Gut microbiota has been linked to PE by previous amplicon sequencing studies. To resolve the PE gut microbiota in a higher taxonomy resolution, we performed shotgun metagenomic sequencing on the fecal samples from 40 early-onset PE and 37 healthy pregnant women. We recovered 1,750 metagenome-assembled genomes (representing 406 species) from the metagenomic dataset and profiled their abundances. We found that PE gut microbiota had enriched in some species belonging to Blautia, Pauljensenia, Ruminococcus, and Collinsella and microbial functions such as the bacitracin/lantibiotics transport system, maltooligosaccharide transport system, multidrug efflux pump, and rhamnose transport system. Conversely, the gut microbiome of healthy pregnant women was enriched in species of Bacteroides and Phocaeicola and microbial functions including the porphyrin and chlorophyll metabolism, pyridoxal-P biosynthesis, riboflavin metabolism, and folate biosynthesis pathway. PE diagnostic potential of gut microbial biomarkers was developed using both species and function profile data. These results will help to explore the relationships between gut bacteria and PE and provide new insights into PE early warning.

Thresholds for Ambulatory Blood Pressure Monitoring Based on Maternal and Neonatal Outcomes in Late Pregnancy in a Southern Chinese Population.

Background In contrast to the general population, outcome-derived thresholds for diagnosing ambulatory hypertension in pregnancy are not yet available. We aimed to identify and compare outcome-derived ambulatory blood pressure (BP) monitoring thresholds for adverse perinatal outcomes by using approaches related and not related to clinic BP in a southern Chinese population. Methods and Results Ambulatory BP monitoring was performed in a cohort of 1768 high-risk participants in late pregnancy who were not taking antihypertensive medications. Participants were followed for composite maternal (severe complications) and neonatal (pregnancy loss, advanced neonatal care, and small for gestational age) outcomes. Modeling of clinic BP-unrelated approaches revealed a nonlinear threshold effect of ambulatory diastolic BP on the composite outcome, with increased risk for daytime ≥79 mm Hg and 24-hour measurement ≥76 mm Hg. For other ambulatory BP components showing linear associations with outcome, the following thresholds were identified: 131 mm Hg for daytime systolic, 121 mm Hg for nighttime systolic, 130 mm Hg for 24-hour systolic, and 73 mm Hg for night-time diastolic BP. These thresholds unrelated to clinic BP were lower than the equivalents yielding a similar probability of outcome to clinic BP of 140/90 mm Hg and were comparable with equivalents to clinic BP of 130/80 mm Hg. Conclusions Using an outcome-derived approach unrelated to clinic BP, we identified rounded thresholds to define ambulatory hypertension in at-risk women in late pregnancy in a southern Chinese population as follows: 130/80 mm Hg for daytime, 120/75 mm Hg for nighttime, and 130/75 mm Hg for 24-hour measurement. For wider clinical applicability and to align both nonpregnancy and pregnancy ambulatory BP monitoring with an outcomes-based approach, prospective, multiethnic, international studies from early pregnancy onward will be required.

Excessive umbilical cord coiling confers risk of elevated nocturnal blood pressure and severe/early-onset preeclampsia.

BACKGROUND: The associations between umbilical cord coiling, feto-placental vascular resistance and maternal blood pressure (BP) are not well understood. METHOD: We retrospectively analyzed 502 pregnant women suspected of hypertensive disorders in the third trimester from a hospital-based cohort, who underwent ambulatory BP monitoring and umbilical artery Doppler velocimetry examinations within 14 days before delivery. By applying quantile regression, a significant quantile-dependent positive association between umbilical cord coiling index and umbilical artery pulsatility index (UAPIMOM; converted to multiples of median) was observed from above 0.75th quantiles for each parameter. RESULTS: Using the cutoffs both at the 0.75th quantile to define high umbilical cord coiling (≥0.28 coils/cm) and high UAPIMOM (≥1.30), respectively, a graded increase in BP level was observed from patients with both low, either high and both high categories. Multivariate linear and quantile regression revealed that the high umbilical cord coiling/high UAPIMOM interaction was significantly correlated with night-time mean DBP level. Moreover, umbilical cord hypercoiling (≥0.3 coils/cm) was significantly correlated with night-time DBP with an average increase of ∼5 mmHg from the 0.05th to 0.70th quantiles and independently predicted the occurrence of severe (odds ratio 2.32, 95% confidence interval: 1.22-4.41) and early-onset (odds ratio 2.43, 95% confidence interval: 1.18-4.97) preeclampsia after adjusting for covariates. Further mediation analysis showed that elevated high UAPIMOM (≥1.30) could explain 11.4% of the umbilical cord hypercoiling → high night-time DBP association. CONCLUSION: Therefore, this retrospective study identifies excessive umbilical cord coiling, and its interaction with increased feto-placental vascular resistance, as novel risk factors for nocturnal BP elevation and preeclampsia.

Prehypertension During Normotensive Pregnancy and Postpartum Clustering of Cardiometabolic Risk Factors: A Prospective Cohort Study.

The nonstratification of blood pressure (BP) levels may underestimate future cardiovascular risk in pregnant women who present with BP levels in the range of prehypertension (120-139/80-89 mm Hg). We prospectively evaluated the relationship between multiple antepartum BP measurements (from 11(+0) to 13(+6) weeks' gestation to term) and the occurrence of postpartum metabolic syndrome in 507 normotensive pregnant women after a live birth. By using latent class growth modeling, we identified the following 3 distinctive diastolic BP (DBP) trajectory groups: the low-J-shaped group (34.2%; DBP from 62.5±5.8 to 65.0±6.8 mm Hg), the moderate-U-shaped group (52.6%; DBP from 71.0±5.9 to 69.8±6.2 mm Hg), and the elevated-J-shaped group (13.2%; DBP from 76.2±6.7 to 81.8±4.8 mm Hg). Notably, the elevated-J-shaped trajectory group had mean DBP and systolic BP levels within the range of prehypertension from 37(+0) and 26(+0) weeks of pregnancy, respectively. Among the 309 women who completed the ≈1.6 years of postpartum follow-up, the women in the elevated-J-shaped group had greater odds of developing postpartum metabolic syndrome (adjusted odds ratio, 6.55; 95% confidence interval, 1.79-23.92; P=0.004) than the low-J-shaped group. Moreover, a parsimonious model incorporating DBP (membership in the elevated-J-shaped group but not in the DBP prehypertension group as identified by a single measurement) and elevated levels of fasting glucose (>4.99 mmol/L) and triglycerides (>3.14 mmol/L) at term was developed, with good discrimination and calibration for postpartum metabolic syndrome (c-statistic, 0.764; 95% confidence interval, 0.674-0.855; P<0.001). Therefore, prehypertension identified by DBP trajectories throughout pregnancy is an independent risk factor for predicting postpartum metabolic syndrome in normotensive pregnant women.

[Evaluation of the diagnostic criteria of gestational metabolic syndrome and analysis of the risk factors].

OBJECTIVES: To investigate gestational multiple metabolic abnormalities aggregation and diagnostic criteria for gestational metabolic syndrome (GMS), and to analyze the risk factors of GMS. METHODS: A cohort study recruiting 309 pregnant women with preeclampsia, 627 pregnant women with gestational diabetes mellitus (GDM) and 1245 normal pregnant women was performed from January 2008 to December 2011 in Guangdong Women and Children's Hospital. Information regarding age, gestational weeks, basic blood pressure, admission blood pressure, height and body mass index(BMI)before pregnancy was recorded. Biochemical indicators including fasting plasma glucose (FPG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), free fatty acids (FFA) were tested. GMS was diagnosed with three or all of the following conditions: (1) overweight and/or obesity before pregnancy (BMI ≥ 25 kg/m(2)); (2) hypertension with blood pressure ≥ 140/90 mm Hg (1 mm Hg = 0.133 kPa); (3) hyperglycemia:diagnosed as GDM; (4) dyslipidemia with TG ≥ 3.23 mmol/L. The incidence of GMS of the three groups were calculated and the risk factors were analyzed. RESULTS: (1) The age, gestational weeks, basic blood pressure, admission blood pressure, BMI before pregnancy of women with preeclampsia and women with GDM were significantly different compared to normal women, respectively (P < 0.01). (2) Biochemical indicators of women with preeclampsia were as following: FPG (4.6 ± 1.0) mmol/L, FINS (10.1 ± 5.6) mU/L, TC (6.3 ± 1.6) mmol/L, TG (3.9 ± 1.8) mmol/L, HDL-C (1.4 ± 0.4) mmol/L, LDL-C (3.0 ± 1.0) mmol/L, FFA (0.8 ± 0.4) mmol/L. And those in women with GDM were: FPG (4.7 ± 0.9) mmol/L, FINS (10.2 ± 5.8) mU/L, TC (5.7 ± 1.3) mmol/L, TG (3.2 ± 1.1) mmol/L, HDL-C (1.4 ± 0.4) mmol/L, LDL-C (2.7 ± 0.9) mmol/L, FFA (0.6 ± 0.3) mmol/L. In normal pregnant women they were: FPG (4.3 ± 0.5) mmol/L, FINS (9.0 ± 4.4) mU/L, TC (5.7 ± 1.1) mmol/L, TG (2.8 ± 1.1) mmol/L, HDL-C (1.5 ± 0.4) mmol/L, LDL-C (2.9 ± 0.8) mmol/L, FFA (0.6 ± 0.2) mmol/L. Statistic differences were found in preeclampsia and GDM women compared to normal women respectively (P < 0.01). (3) The prevalence of GMS in preeclampsia group and in GDM group was 26.2% (81/309) and 13.6% (85/627), statistically different from that of the control group (0)(P < 0.01). (4) Compared to normal women, women with preeclampsia had higher risk of developing GMS (OR = 1.62, 95%CI 1.31 - 2.00, P < 0.01). The risk factors were BMI (OR = 1.29, 95%CI 1.13 - 1.47) and TG (OR = 2.49, 95%CI 1.87 - 3.31). Also, women with GDM had higher risk of developing GMS than normal women (OR = 1.27, 95%CI 1.09 - 1.49, P < 0.01), and the risk factors were BMI (OR = 1.13, 95%CI 1.04 - 1.23) and TG (OR = 1.16, 95%CI 1.02 - 1.33). TG was the independent risk factor in both preeclampsia women and GDM women (P < 0.01, P < 0.05). HDL-C seemed to have less importance in identifying GMS (P > 0.05). CONCLUSIONS: According to the GMS diagnostic criteria used in this study, some preeclampsia patients and some GDM women had aggregation of multiple metabolic abnormalities including pre-pregnancy overweight/obesity, hyperglycemia, high blood pressure and dyslipidemia. TG was the independent risk factor for GMS. HDL-C seemed to have less importance in identifying GMS.