INTRODUCTION

Preeclampsia, a multisystemic, multifactorial disorder, is the second leading cause of maternal deaths in the Philippines. It is diagnosed by the presence of hypertension and proteinuria or significant end-organ damage in a parturient carrying at least 20 weeks age of gestation. Proteinuria, in preeclampsia, is diagnosed by having 300 mg protein in a 24-h urine sample, a 0.3 mg/mg urine protein:creatinine ratio, or 2+ protein on a urine dipstick. All currently available diagnostic tests have their advantages and disadvantages. A novel diagnostic test, the spot ratiometric urine protein:creatinine dipstick test kit, was developed to meet the limitations of the currently available methods. Early diagnosis of preeclampsia will help in the prompt management to decrease maternal and neonatal complications.

The objective of this study was to compare the diagnostic accuracy of the spot ratiometric urine protein:creatinine dipstick test (SUPCR) in comparison to 24-h urine protein (24HUP) in the diagnosis of preeclampsia.

A non-experimental cross-sectional study comparing spot ratiometric urine protein:creatinine dipstick test (SUPCR) to 24HUP and urine dipstick among parturients with elevated blood pressure in a tertiary hospital to diagnose preeclampsia.

A total of 190 parturients were included. SUPCR showed a sensitivity of 88.36%, a specificity of 93.18%, and a likelihood ratio (LR) of 12.96. Urine dipstick (2+) showed a sensitivity of 26.03%, a specificity of 95.45%, and an LR of 5.73.

SUPCR can be an alternative to 24HUP in detecting preeclampsia among pregnant patients due to its high sensitivity, specificity, and LR values. This novel diagnostic can be used in low-resource settings due to its fast results, low cost, and ease of use.

INTRODUCTION

Hypertension disorders in pregnancy cause significant number of maternal morbidity and mortality. In local statistics for the years 2019–2022, hypertension causes 13.8% of the maternal mortality. Thus, accurate diagnosis of Preeclampsia is crucial to prevent disease progression and to provide timely intervention for improved maternal outcomes. It is widely accepted that 24-h urine protein is the gold standard for detecting proteinuria in patients with preeclampsia, but since the process of collection is too long and complicated, recent studies focus on other less complex yet reliable methods of determining proteinuria for the diagnosis of preeclampsia, including the protein–creatinine ratio (PrCr) dipstick tests.

This study aims to determine the diagnostic accuracy of urine protein detection in patients with preeclampsia, using a urine PrCr dipstick test.

A prospective, cross-sectional study using purposive sampling was used in this study. A total of 153 admitted pregnant patients with gestational hypertension and preeclampsia, without other comorbidities or significant past medical history, were tested for proteinuria using the 24-h urine protein test and urine PrCr dipstick test. Statistical analysis to assess diagnostic accuracy used was the sensitivity, specificity, positive predictive value, and negative predictive value.

The urine PrCr dipstick test has comparable diagnostic accuracy with 24-h urine protein test in detecting proteinuria, with a sensitivity of 88%, a specificity of 64%, and a high positive predictive value of 94%. It is a simpler, faster, yet useful alternative to a more tedious, time and resource consuming process of urine collection in the 24-h urine protein in identifying patients with proteinuria, and therefore, preeclampsia.

Pregnancy ; Female ; Humans ; Pre-Eclampsia/epidemiology* ; Prenatal Exposure Delayed Effects ; Case-Control Studies ; China/epidemiology* ; Fluorocarbons/toxicity*

Objective: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on pregnancy outcomes, especially the relationship between OSAS and hypertensive disorders in pregnancy (HDP). Methods: A total of 228 pregnant women with high risk of OSAS who underwent sleep monitoring during pregnancy in Peking University People's Hospital from January 2021 to April 2022 were collected by reviewing their medical records for retrospective analysis. According to the diagnosis of OSAS, the pregnant women were divided into OSAS group (105 cases) and non-OSAS group (123 cases). The non-parametric Mann-Whitney U test, χ² test or Fisher's exact test were used to compare the general data and maternal and fetal outcomes between the two groups, and the occurrence of each type of HDP was further compared. Results: (1) Compared with the non-OSAS group, the median pre-pregnancy body mass index (23.6 vs 27.6 kg/m²) and the proportion of snoring [28.9% (33/114) vs 59.2% (61/103)] in the OSAS group were higher, and the differences were both statistically significant (both P<0.001). (2) The incidence of HDP [67.6% (71/105) vs 39.0% (48/123)] and gestational diabetes mellitus [GDM; 40.0% (42/105) vs 26.8% (33/123)] of pregnant women in the OSAS group were higher than those in the non-OSAS group, and the median delivery week was shorter than that in the non-OSAS group (38.4 vs 39.0 weeks). The differences were all statistically significant (all P<0.05). Between-group differences for the delivery way, postpartum hemorrhage, the rate of intensive care unit admission, preterm birth, small for gestational age infants, neonatal asphyxia, the rate of neonatal intensive care unit admission, newborn birth weight and the proportion of umbilical artery blood pH<7.00 were not statistically significant (all P>0.05). (3) Compared with the non-OSAS group, the incidence of chronic hypertension [11.4% (14/123) vs 22.9% (24/105)] and chronic hypertension with superimposed pre-eclampsia [11.4% (14/123) vs 30.5% (32/105)] were higher in the OSAS group, and the differences were both statistically significant (both P<0.01). Conclusion: OSAS is related to HDP (especially chronic hypertension and chronic hypertension with superimposed pre-eclampsia) and GDM, which could provide a practical basis for the screening, diagnosis and treatment of OSAS in pregnant women at high risk.
Infant, Newborn ; Pregnancy ; Infant ; Humans ; Female ; Pre-Eclampsia/epidemiology* ; Hypertension, Pregnancy-Induced/epidemiology* ; Retrospective Studies ; Premature Birth ; Sleep Apnea, Obstructive/epidemiology* ; Diabetes, Gestational/epidemiology*

Objective: To investigate the expression change of the Mas1 receptor in the placenta of healthy pregnant women during different gestation periods, analyze the expression level of the Mas1 receptor in the placenta of pre-eclampsia (PE) patients, and its biological function in trophoblast cells. Methods: Placental villous tissues were collected from normal pregnant women in early, mid and late pregnancy. Human trophoblast stem cells were isolated and cultured from early pregnancy villous tissues. The expression of the Mas1 receptor was detected by fluorescence immunoassay and real-time fluorescence quantitative PCR. In a case-control study, patients with full-term PE were selected as the case group and healthy women with full-term pregnancy were selected as the control group. Placental villus tissues were collected from both groups. Immunofluorescence chemistry and immunoprotein blotting were used to study the changes in Mas1 receptor expression in PE. Mas1 receptor agonists and blockers induced HTR8/Svneo cells and BeWo cells, and the effects of the Mas1 receptor on the proliferation and migration of trophoblast cells were detected by the CCK8 proliferation test and scratch test. Results: Eight cases were included in early pregnancy, seven cases in mid-pregnancy and six cases in late pregnancy. Mas1 receptors in normal placental villi tissue were mainly expressed in human trophoblast stem cell membranes and cytoplasm, and the expression of Mas1 receptor mRNA in villi tissue was significantly higher in late pregnancy than in mid-pregnancy. There were 24 cases included in the case group and 12 cases in the control group. Mas1 receptor expression in placental villi was significantly lower in the case group compared to the control group; Activation/inhibition of the Mas1 receptor had no significant effect on the proliferation of HTR8/Svneo cells and BeWo cells. Activated Mas1 receptor had no significant effect on the migration ability of HTR8/Svneo cells. Conclusion: Mas1 receptors are expressed in placental villous tissue and their expression varies with gestation. Mas1 receptor expression is reduced in PE patients, but it does not affect the value-added or migratory function of trophoblast cells.
Humans ; Female ; Pregnancy ; Placenta ; Trophoblasts ; Case-Control Studies ; Pre-Eclampsia ; Gene Expression

OBJECTIVE: To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD). METHODS: This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD. RESULTS: There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE. CONCLUSION Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Pregnancy Outcome ; Retrospective Studies ; Abortion, Spontaneous/etiology* ; Undifferentiated Connective Tissue Diseases ; Pre-Eclampsia/epidemiology* ; Lupus Erythematosus, Systemic ; Risk Factors ; Leukopenia ; Pregnancy Complications/epidemiology* ; Disease Progression ; Connective Tissue Diseases/epidemiology*

Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.
Pregnancy ; Female ; Humans ; Placenta ; Fetal Growth Retardation/etiology* ; Pre-Eclampsia/pathology* ; Reactive Oxygen Species ; Hypoxia/pathology* ; Pregnancy Complications/pathology* ; Endoplasmic Reticulum Stress

OBJECTIVES: To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE). METHODS: Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups. RESULTS: Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05). CONCLUSIONS The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.
Female ; Pregnancy ; Infant, Newborn ; Humans ; Genetic Predisposition to Disease ; HLA-DRB1 Chains/genetics* ; Pre-Eclampsia/genetics* ; Gene Frequency ; Genotype ; Polymorphism, Single Nucleotide ; Alleles

Objective: To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of ~12 weeks from community hospitals in Tianjin. Latent class growth modeling (LCGM) was used to model the blood pressure trajectories. Methods: This was a large prospective cohort study. The study enrolled pregnant women of ~12 weeks of gestation in 19 community hospitals in Tianjin from November 1, 2016 to May 30, 2018. We obtained related information during 5 antepartum examinations before gestational week 28, i.e., week 12, week 16, week 20, week 24 and week 28. LCGM was used to model longitudinal systolic (SBP) and diastolic blood pressure (DBP) trajectories. For the association study, the predictors were set as SBP and DBP trajectory membership (built separately), the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation. Results: A total of 5 809 cases with known pregnant outcomes were documented. After excluding 249 cases per exclusion criteria, 5 560 cases with singleton pregnancy were included for final analysis. There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort. Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia. Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for SBP latent classification trajectory_ 4 was 4.023 (95%CI: 2.368 to 6.835, P<0.001), and the OR for SBP latent classification trajectory_3 was 1.854 (95%CI: 1.223 to 2.811, P=0.004). Logistic regression showed that: using the DBP latent classification trajectory_1 as the reference group, the OR for DBP latent classification trajectory_4 was 4.100 (95%CI: 2.571 to 6.538, P<0.001), and 2.632 (95%CI: 1.570 to 4.414, P<0.001) for DBP latent classification trajectory_2. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for DBP_traj_4 was 2.527 (95%CI: 1.534 to 4.162, P<0.001), and the OR for DBP_traj_3 was 1.297 (95%CI: 0.790 to 2.128, P=0.303), and 2.238 (95%CI: 1.328 to 3.772, P=0.002) for DBP_traj_2. Therefore, BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia. Receiver operating characteristic (ROC) curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories. Conclusion: By applying LCGM, we for the first time identified distinctive BP trajectories from gestational week 12 to 28, which can independently predict the development of preeclampsia after 28 weeks of gestation.
Female ; Humans ; Pregnancy ; Infant ; Blood Pressure ; Pre-Eclampsia/diagnosis* ; Prospective Studies ; Gestational Age ; Alanine Transaminase ; Hemoglobins

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Body Mass Index ; Overweight/epidemiology* ; Premature Birth/epidemiology* ; Pre-Eclampsia/epidemiology* ; Cohort Studies ; Eclampsia ; Incidence ; Risk Factors ; Thinness/epidemiology*