Cardiometabolic health after first pregnancy: Associations with social determinants of health. A nuMoM2b-HHS study.

Study objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.

Implementation of a pharmacogenomics consult service to support the INGENIOUS trial.

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding.

Chronic villitis of unknown etiology and massive chronic intervillositis have similar immune cell composition.

INTRODUCTION: Chronic villitis of unknown etiology (CVUE) and massive chronic intervillositis (MCI) are placental lesions associated with infiltration of mononuclear cells in the chorionic villi and the intervillous spaces, respectively. It is not well known whether immune cells in CVUE and MCI have similar phenotypic characteristics. METHODS: A cross-sectional study of third trimester placentas was conducted to identify immune cell subpopulations in CVUE and MCI (n = 17/group). CVUE was diagnosed with H&E staining and antibody to CD3 in serial sections; and MCI, by the presence of massive infiltration of mononuclear cells in the intervillous spaces. Immune cells, ICAM-1 expression and nuclear factor κB (NF-κB) activation were determined immunohistochemically. RESULTS: CVUE and MCI showed similar infiltrates, mainly CD68+ and CD3+ cells. Most cells (>80%) were CD45RB+, and one third were CD45RO+ in both lesions. There were slightly more CD8+ than CD4+ cells in both CVUE and MCI. More than 90% of cells in CVUE and MCI were ICAM-1+ with NFκB nuclear localization. Syncytiotrophoblast ICAM-1 expression was significantly (p < 0.001) higher in MCI (mean of 81.0; range of 71.6-86.0) than in CVUE (52.4; 36.4-59.4) or normal placentas (0.2; 0.0-0.6). Both, failure of physiologic transformation of spiral arteries and placental atherosclerosis-like lesions of atherosis were significantly more frequent in MCI than in CVUE or normal placentas (p = 0.044 and p = 0.007, respectively). DISCUSSION: These finding suggest that MCI and CVUE have very similar infiltration of immune cells although MCI has more severe placental lesions.

A collinear self-emission and laser-backlighting imaging diagnostic.

In this work we demonstrate a design for obtaining laser backlighting (e.g., interferometry) and time-resolved extreme ultraviolet self-emission images along the same line-of-sight. This is achieved by modifying a single optical component in the laser collection optics with apertures and pinhole arrangements suitable for single or multiple frame imaging onto a gated detector, such as a microchannel plate. Test results for exploding wire experiments show that machining of the optic does not affect the overall quality of the recovered laser images, and that, even with a multiple frame system, the area sacrificed to achieve collinear imaging is relatively small. The diagnostics can therefore allow direct correlation of laser and self-emission images and their derived quantities, such as electron density in the case of interferometry. Simple methods of image correlation are also demonstrated.

The current state of therapeutic drug trials in pregnancy.

The majority of pregnant women take prescription drugs during their pregnancy. Given the multitude of physiologic changes incumbent in pregnancy, accurate clinical trial data on drugs in pregnancy are crucial. This report summarizes the 264 registered clinical trials in the past two years. With many of these drug trials being pharmacokinetic and placebo-controlled studies, therapeutic drug trials are becoming more common.

A Semi-Mechanistic Metabolism Model of CYP3A Substrates in Pregnancy: Predicting Changes in Midazolam and Nifedipine Pharmacokinetics.

Physiological changes in pregnancy, including changes in body composition and metabolic enzyme activity, can alter drug pharmacokinetics. A semi-mechanistic metabolism model was developed to describe the pharmacokinetics of two cytochrome P450 3A (CYP3A) substrates, midazolam and nifedipine, in obstetrics patients. The model parameters were optimized to fit the data of oral midazolam pharmacokinetics in pregnant women, by increasing CYP3A-induced hepatic metabolism 1.6-fold in the model with no change in gut wall metabolism. Fetal metabolism had a negligible effect on maternal plasma drug concentrations. Validation of the model was performed by applying changes in volume of distribution and metabolism, consistent with those observed for midazolam, to the pharmacokinetics parameters of immediate-release nifedipine in healthy volunteers. The predicted steady-state areas under the concentration-time curve (AUCs) for nifedipine were within 15% of the data observed in pregnant women undergoing treatment for preterm labor. This model predicts the pharmacokinetics of two CYP3A substrates in pregnancy, and may be applicable to other CYP3A substrates as well.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e2; doi:10.1038/psp.2012.5; advance online publication 26 September 2012.

Progestogen for preventing miscarriage.

BACKGROUND: Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progestogens. Therefore, progestational agents have been used, beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage. OBJECTIVES: To determine the efficacy and safety of progestogens as a preventative therapy against miscarriage. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (April 2003), CENTRAL, MEDLINE (1966 to April 2003), EMBASE (1980 to April 2003), CINAHL (1982 to April 2003), NHMRC Clinical Trials Register (April 2003) and Meta-Register (April 2003). We searched references from relevant articles, attempting to contact authors where necessary, and contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage. DATA COLLECTION AND ANALYSIS: Thirty trials were identified in the initial search. At least, two reviewers assessed trial quality and extracted data. Data for all outcomes were in dichotomous form and the Peto odds ratio was used in the meta-analysis for all comparisons. MAIN RESULTS: Fourteen trials (1988 women) met the inclusion criteria. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.83 to 1.34) and no statistically significant difference in the incidence of adverse effect in either mother or baby. In a subgroup analysis of three trials involving women who had recurrent miscarriages (three or more consecutive miscarriages), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (OR 0.39, 95% CI 0.17 to 0.91). No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment. REVIEWER'S CONCLUSIONS: There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid pregnancy. However, further trials in women with a history of recurrent miscarriage may be warranted, given the trend for improved live birth rates in these women and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence.

Comparing ambulatory spot urine protein/creatinine ratios and 24-h urine protein measurements in normal pregnancies.

OBJECTIVE: To determine whether a single specimen protein/creatinine ratio correlated with a 24-h urine protein measurement in ambulatory women with normal pregnancies. METHODS: A prospective cohort was evaluated of healthy women performing a 24-h urine collection and spot urine measurement for protein and creatinine in each trimester and the postpartum period. Data were analyzed to establish the correlation of values and the reliability of cut-off values. RESULTS: Fifty-eight women were enrolled in the study. Thirty-three completed at least one measurement. Three (5.1%) developed pre-eclampsia. With the use of linear regression, the spot protein/creatinine ratio correlated with the 24-h protein measurement in the first trimester and postpartum periods only (p < 0.001 and p < 0.043, respectively). It did not correlate in the second or third trimester (p = 0.637 and p = 0.290, respectively). CONCLUSION: In this population, the protein/creatinine ratio correlated only with the 24-h urine protein measurement in the first trimester and postpartum periods. In the periods of pregnancy where physiological changes are most prevalent, the ratio does not predict total urinary protein reliably.

Laceration injury at cesarean section.

OBJECTIVE: To determine the infant laceration injury rate during Cesarean sections at Naval Medical Center, San Diego and to describe risk factors associated with this complication. METHODS: Retrospective chart review of all infants born between 1 January 1996 and 31 December, 1999 identified by computer coding as having sustained a birth injury. Fifty randomly selected maternal records of Cesarean sections without infant lacerations were reviewed and analyzed as a control group. RESULTS: Our Cesarean section rate during the time was 16.5% with a laceration injury rate of 0.74%. When compared to controls, there was no difference in operative indication, type of Cesarean section, or any demographic information between the two groups. Male infant gender (p = 0.027) and ruptured membranes (p = 0.019) showed a statistically significant difference between the two groups. CONCLUSIONS: Laceration injury to the infant during Cesarean section is associated with a laboring uterus. This is an important complication that should be part of preoperative counselling and should be documented appropriately when it occurs.

Do physicians discuss HIV and AIDS with patients? A survey of physician practices.

HIV and AIDS continue to be major concerns to the health care community and the world around them. Preventive efforts and education have been the focus of the fight against AIDS thus far. By the year 2000, 75% of physicians are expected to conduct risk-reduction counseling for patients regularly. Previous studies show that a smaller percentage "routinely" follow this recommendation. The purpose of our study was to assess with what percentage of patients physicians discuss several HIV/ AIDS-related topics, what percentage of their patients are considered at risk for infection, and how comfortable the physicians are with their knowledge level and discussing the subject matter. We sent surveys to the last five graduating classes from St. Louis University School of Medicine and to 169 physician preceptors in the community. The survey asked about patients considered at risk, physician comfort level with HIV/ AIDS, the percentage of patients they discuss various HIV/AIDS topics with, and his or her preparedness for these discussions. Total responses were 464 (53.7%) representing all areas of medicine. Most of the physicians (72.9%) consider 0-25% of their patients at risk for HIV/AIDS. Eighty-one percent claim they are moderately or very comfortable discussing the material with patients and more than 90% feel they have at least adequate knowledge. Most of the respondents discuss the HIV/ AIDS topics with 0-25% of patients. Recent medical school graduates and primary care physicians are more comfortable with HIV/AIDS and discuss the surveyed topics with a higher percentage of patients.