Using Middle Cerebral Artery Doppler Ultrasound to Predict Clinical Chorioamnionitis After Preterm Prelabor Rupture of Membranes.

BACKGROUND: In neonates, blood flow to the brain as measured by peak systolic velocity (PSV) in the middle cerebral artery (MCA) is altered in pregnancies affected by chorioamnionitis. OBJECTIVE: We aim to determine whether PSV and other measures of flow in the MCA in the fetus are altered prior to the development of clinical chorioamnionitis following preterm prelabor rupture of membranes (PPROM). METHODS:  This was a prospective observational study. Fifty patients from one institution were recruited after being diagnosed with PPROM between 23 weeks zero days and 33 weeks six days gestation. We performed measurements of the PSV in the fetal MCA on a weekly basis following PPROM and used the value taken closest to the time of delivery for our statistical analysis. The primary outcome assessed was clinical chorioamnionitis, and the exposure of interest was MCA PSV. Additional independent variables of interest were other Doppler measures of the MCA. Secondary outcomes included histological chorioamnionitis and other measures of neonatal health, including sepsis, days in the neonatal intensive care unit (NICU), and death. RESULTS: Of the 50 patients recruited to our study, eight (16%) developed clinical chorioamnionitis, similar to previously reported values in the general population. The PSV in the MCA was not significantly associated with the development of clinical chorioamnionitis. However, an elevated MCA pulsatility index (PI), a measure of resistance to flow, was associated with a higher probability of developing clinical chorioamnionitis. CONCLUSION:  There does not appear to be a difference in the PSV of the MCA of fetuses in pregnancies following PPROM with impending chorioamnionitis. However, elevated PI in the MCA could be a marker of impending chorioamnionitis in PPROM. Larger studies are needed to confirm these findings.

Quick Sequential Organ Failure Assessment: Modifications for Identifying Maternal Morbidity and Mortality in Obstetrical Patients.

OBJECTIVE: Screening tools, including the Systemic Inflammatory Response Syndrome (SIRS) criteria and Sequential Organ Failure Assessment (SOFA) criteria, have not been validated in the pregnant population. We aimed to determine if pregnancy-specific modifications to the quick SOFA (qSOFA) can improve prediction of severe maternal morbidity in pregnant women with serious infections. STUDY DESIGN: We performed a retrospective cohort study of pregnant patients with severe infections admitted to a single institution from January 1, 2011, through December 31, 2017. The primary outcome was severe maternal morbidity, defined as a composite of adverse maternal outcomes: intensive care unit (ICU) admission for >48 hours, need for invasive monitoring (central line or arterial line), intubation, pharmacologic hemodynamic support (intravenous vasopressors or inotropes), and/or maternal death. A logistic regression was then applied and the resulting predictors were analyzed individually and in combination with receiver operating characteristic (ROC) curves to modify qSOFA for pregnancy, that is, qSOFA-P. RESULTS: Analysis of 104 pregnant patients with severe infections found that the standard qSOFA did not accurately predict severe maternal morbidity (ROC area under the curve [AUC] = 0.54, p = 0.49, sensitivity = 0.38, and specificity = 0.70). Pregnancy-specific modifications or "qSOFA-P" (respiratory rate [RR] ≥ 35 breaths/minute and systolic blood pressure [SBP] ≤ 85 mm Hg) significantly improved prediction of severe maternal morbidity (AUC = 0.77, p < 0.001, sensitivity = 0.79, and specificity = 0.74). CONCLUSION: The standard qSOFA is a poor screening tool in the prediction of severe maternal morbidity in pregnant patients with infections. A pregnancy-specific screening system, qSOFA-P, improved prediction of severe maternal morbidity in pregnant women with severe infections. Further prospective and large multicenter studies are needed to validate this scoring system in pregnant women. KEY POINTS: · Validated scoring systems for evaluating pregnant patients with sepsis are needed.. · Modifications to existing systems may improve the evaluation of pregnant patients with sepsis.. · The qSOFA-P (RR ≥ 35 breaths/minute and SBP ≤ 85 mm Hg) includes modifications to qSOFA, and improves the detection of patients who would develop severe maternal morbidity...

Risk factors for needing postpartum antihypertensive medications with hypertensive disorders: Timing of diagnosis, presence of proteinuria, and severity of disease.

OBJECTIVES: Evaluate the association between the need for post-partum antihypertensive medications in patients with hypertensive disorders of pregnancy (HDP) and the following: timing of disease onset (antepartum vs. intrapartum), presence of proteinuria, and severity of disease. STUDY DESIGN: This was a retrospective cohort study. We reviewed the charts of 204 patients diagnosed with HDP: 106 were diagnosed antepartum and 98 diagnosed intrapartum. Patients withchronichypertensionwereexcluded. MAIN OUTCOME MEASURES: The need for outpatient antihypertensive medications at time of hospital discharge was the primary outcome. We performed logistic regression of covariates and a stratified analysis for each specific HDP (gestational hypertension (GHTN), preeclampsia and preeclampsia with severe features). RESULTS: While the diagnosis of HDP in the antepartum period was a statistically significant risk factor for needing postpartum anti-hypertensive medications at discharge in bivariate analysis RR 2.07 (1.27-3.37), p = 0.001, it did not remain significant after correction for the covariates RR 1.41 (0.45-4.49), P = 0.55. However, the presence of proteinuria was an independent risk factor after logistic regression. Compared to GHTN, there was a significant difference in the need for postpartum anti-hypertensive medications in patients with preeclampsia OR 10.70 (1.54-74.42), p = 0.017 and in preeclampsia with severe features OR 112.14 (20.05-627.22), p < 0.001. CONCLUSION: Timing of onset of HDP (antepartum vs. intrapartum) was not an independent risk factor for needing antihypertensive medications postpartum. However, proteinuria and the presence of severe features were. Patients with proteinuria and those with severe disease may warrant closer surveillance in the post-partum period than those without proteinuria.

Epigenetics and the vaginal microbiome: influence of the microbiota on the histone deacetylase level in vaginal epithelial cells from pregnant women.

BACKGROUND: Histone deacetylase (HDAC) influences the acetylation status of histones at gene promotor loci, providing an epigenetic mechanism that regulates gene expression. METHODS: We determined if variations in the composition of the vaginal microbiome in pregnant women were associated with alterations in the level of HDAC1 in vaginal epithelial cells and whether this influenced the concentration of compounds present in vaginal fluid. Vaginal epithelial cells were obtained from 150 women in their first trimester of pregnancy, lysed and assayed for HDAC1 by ELISA. Composition of the vaginal microbiome was determined by classification of sequences amplified from the V1-V3 region of bacterial ribosomal 16S rRNA genes. Vaginal secretions were assayed for total protein, matrix metalloproteinase (MMP)-8, the 70kDa heat shock protein (hsp70) and the D- and L-lactic acid isomers. RESULTS: Lactobacilli were numerically dominant in 119 (79.3%) of the women, with Lactobacillus crispatus being the most prevalent (45.3% of women). Gardnerella was the most prevalent non-Lactobacillus species (10.7% of women). The median HDAC1 level in epithelial cells was 6.1 ng/mL when lactobacilli predominated vs. 20.5 ng/mL when non-lactobacilli were dominant (P=0.0039). Levels were lowest when L. crispatus was dominant (3.8 ng/mL) and highest with Streptococcus dominance (38.1 ng/mL). The concentration of HDAC1 was negatively correlated with the D-lactic acid level (P=0.0183) and positively correlated with concentrations of MMP-8 and hsp70 (P<0.0001) in the vaginal fluid. CONCLUSIONS: We propose that the composition of the vaginal microbiome and level of D-lactic acid, by influencing the HDAC1 level in vaginal epithelial cells, may epigenetically contribute to variations in the concentration of compounds in vaginal fluid.

Properties of Epithelial Cells and Vaginal Secretions in Pregnant Women When Lactobacillus crispatus or Lactobacillus iners Dominate the Vaginal Microbiome.

OBJECTIVE: Our objective was to determine differences in properties of vaginal epithelial cells and the composition of vaginal secretions when Lactobacillus crispatus or Lactobacillus iners are numerically dominant in the vaginal microenvironment of pregnant women. METHODS: The vaginal microbiomes of 157 first-trimester pregnant women were identified by classifying partial 16S gene sequences amplified from the V1 to V3 region of bacterial ribosomal 16S RNA genes. The extent of autophagy and cell stress in vaginal epithelial cells was determined by measuring the intracellular levels of p62 and the inducible 70-kDa heat shock protein (hsp70). Vaginal secretions were analyzed using a colorimetric assay for d- and l-lactic acid and by enzyme-linked immunosorbent assay for matrix metalloproteinase 8, neutrophil gelatinase-associated lipocalin, α-amylase, hyaluronan, calprotectin, S100A8, and extracellular matrix metalloproteinase inducer (EMMPRIN). RESULTS: L. crispatus was dominant in 69 (43.9%) women, while L iners dominated in 23 (14.6%) women. The median epithelial p62 levels were 0.41 and 4.26 ng/mL in women with L crispatus or L iners dominance, respectively ( P = .0035). The corresponding median hsp70 levels were 4.24 and 14.50 ng/mL, respectively ( P < .0001). The d-lactic acid concentration in vaginal fluid was highest in association with L crispatus dominance, while all other vaginal fluid compounds except for EMMPRIN were highest when L iners was dominant ( P< .03). CONCLUSION: Epithelial cells exhibit a higher level of autophagy, lower induction of stress-related hsp70, and release lower level of mediators when L crispatus is most abundant as compared to when L iners dominates the vaginal microbiota.

Chlamydia trachomatis: the Persistent Pathogen.

Chlamydia trachomatis is an obligate intracellular bacterium whose only natural host is humans. Although presenting as asymptomatic in most women, genital tract chlamydial infections are a leading cause of pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. C. trachomatis has evolved successful mechanisms to avoid destruction by autophagy and the host immune system and persist within host epithelial cells. The intracellular form of this organism, the reticulate body, can enter into a persistent nonreplicative but viable state under unfavorable conditions. The infectious form of the organism, the elementary body, is again generated when the immune attack subsides. In its persistent form, C. trachomatis ceases to produce its major structural and membrane components, but synthesis of its 60-kDa heat shock protein (hsp60) is greatly upregulated and released from the cell. The immune response to hsp60, perhaps exacerbated by repeated cycles of productive infection and persistence, may promote damage to fallopian tube epithelial cells, scar formation, and tubal occlusion. The chlamydial and human hsp60 proteins are very similar, and hsp60 is one of the first proteins produced by newly formed embryos. Thus, the development of immunity to epitopes in the chlamydial hsp60 that are also present in the corresponding human hsp60 may increase susceptibility to pregnancy failure in infected women. Delineation of host factors that increase the likelihood that C. trachomatis will avoid immune destruction and survive within host epithelial cells and utilization of this knowledge to design individualized preventative and treatment protocols are needed to more effectively combat infections by this persistent pathogen.