Discussion required for correct interpretation

Thank you for the opportunity to comment on the editorial by Romero and colleagues [1], which raises a number of important and interesting questions. Such discussion is mandatory if results of scientific techniques such as gene array are to be correctly interpreted and used as the basis for future improvements in patient care

Antibiotic Prophylaxis for Presumptive Group B Streptococcal Infection in Preterm Premature Rupture of the Membranes: Effect on Neonatal and Maternal Infectious Morbidity

Objective: The purpose of this study was to determine if the prevalence of neonatal and maternal infectious morbidity in patients with preterm premature rupture of membranes (PROM) who received ampicillin prophylaxis for presemptive group B streptococcal colonization is increased compared to those who received no prophylaxis

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

BackgroundPreterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition.MethodsSamples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes.ResultsThe largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions.ConclusionsThe results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection

Labor-associated gene expression in the human uterine fundus, lower segment, and cervix

Background Preterm labor, failure to progress, and postpartum hemorrhage are the common causes of maternal and neonatal mortality or morbidity. All result from defects in the complex mechanisms controlling labor, which coordinate changes in the uterine fundus, lower segment, and cervix. We aimed to assess labor-associated gene expression profiles in these functionally distinct areas of the human uterus by using microarrays. Methods and Findings Samples of uterine fundus, lower segment, and cervix were obtained from patients at term (mean +/- 6 SD = 39.1 +/- 0.5 wk) prior to the onset of labor (n = 6), or in active phase of labor with spontaneous onset (n = 7). Expression of 12,626 genes was evaluated using microarrays ( Human Genome U95A; Affymetrix) and compared between labor and non-labor samples. Genes with the largest labor-associated change and the lowest variability in expression are likely to be fundamental for parturition, so gene expression was ranked accordingly. From 500 genes with the highest rank we identified genes with similar expression profiles using two independent clustering techniques. Sets of genes with a probability of chance grouping by both techniques less than 0.01 represented 71.2%, 81.8%, and 79.8% of the 500 genes in the fundus, lower segment, and cervix, respectively. We identified 14, 14, and 12 those sets of genes in the fundus, lower segment, and cervix, respectively. This enabled networks of coregulated and co-expressed genes to be discovered. Many genes within the same cluster shared similar functions or had functions pertinent to the process of labor. Conclusions Our results provide support for many of the established processes of parturition and also describe novel-to-labor genes not previously associated with this process. The elucidation of these mechanisms likely to be fundamental for controlling labor is an important prerequisite to the development of effective treatments for major obstetric problems - including prematurity, with its long-term consequences to the health of mother and offspring

Prescription and Other Medication Use in Pregnancy

OBJECTIVE: To characterize prescription and other medication use in a geographically and ethnically diverse cohort of women in their first pregnancy. METHODS: In a prospective, longitudinal cohort study of nulliparous women followed through pregnancy from the first trimester, medication use was chronicled longitudinally throughout pregnancy. Structured questions and aids were used to capture all medications taken as well as reasons they were taken. Total counts of all medications taken including number in each category and class were captured. Additionally, reasons the medications were taken were recorded. Trends in medications taken across pregnancy and in the first trimester were determined. RESULTS: Of the 9,546 study participants, 9,272 (97.1%) women took at least one medication during pregnancy with 9,139 (95.7%) taking a medication in the first trimester. Polypharmacy, defined as taking at least five medications, occurred in 2,915 (30.5%) women. Excluding vitamins, supplements, and vaccines, 73.4% of women took a medication during pregnancy with 55.1% taking one in the first trimester. The categories of drugs taken in pregnancy and in the first trimester include the following: gastrointestinal or antiemetic agents (34.3%, 19.5%), antibiotics (25.5%, 12.6%), and analgesics (23.7%, 15.6%, which includes 3.6%; 1.4% taking an opioid pain medication). CONCLUSION: In this geographically and ethnically diverse cohort of nulliparous pregnant women, medication use was nearly universal and polypharmacy was common

Sleep During Pregnancy: The nuMoM2b Pregnancy and Sleep Duration and Continuity Study

Study Objectives: To characterize sleep duration, timing and continuity measures in pregnancy and their association with key demographic variables. Methods: Multisite prospective cohort study. Women enrolled in the nuMoM2b study (nulliparous women with a singleton gestation) were recruited at the second study visit (16-21 weeks of gestation) to participate in the Sleep Duration and Continuity substudy. Women <18 years of age or with pregestational diabetes or chronic hypertension were excluded from participation. Women wore a wrist activity monitor and completed a sleep log for 7 consecutive days. Time in bed, sleep duration, fragmentation index, sleep efficiency, wake after sleep onset, and sleep midpoint were averaged across valid primary sleep periods for each participant. Results: Valid data were available from 782 women with mean age of 27.3 (5.5) years. Median sleep duration was 7.4 hours. Approximately 27.9% of women had a sleep duration of 9 hours. In multivariable models including age, race/ethnicity, body mass index, insurance status, and recent smoking history, sleep duration was significantly associated with race/ethnicity and insurance status, while time in bed was only associated with insurance status. Sleep continuity measures and sleep midpoint were significantly associated with all covariates in the model, with the exception of age for fragmentation index and smoking for wake after sleep onset. Conclusions: Our results demonstrate the relationship between sleep and important demographic characteristics during pregnancy

Feto-maternal trafficking of exosomes in murine pregnancy models

Timing and initiation of labor are well-orchestrated by signals communicated between the fetal and maternal compartments; however, how these signals are communicated is not completely understood. Fetal exosomes, intercellular signaling vesicles, may play a key role in the process. The objective of this study was to evaluate exosome trafficking in vivo from fetal to maternal compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational day 16 and 17 with exosomes isolated from primary human amnion epithelial cells fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR). All our analyses were performed on samples collected on Day 18. After 24 h, mice were imaged using Bruker MS FX PRO In vivo Imager and tissues were collected. In vivo imaging of mouse showed fluorescence in the uterus, on the exosome-injected side whereas the uterine tissues from the uninjected side and saline and dye alone injected animals remained negative. Histological analysis of placenta showed exosome migration from the fetal to the maternal side of the placenta. Fluorescence released from exosomes was seen in maternal blood samples as well as in maternal uterus and kidneys. This study demonstrates that exosomal cargo can be carried through systemic route from the fetal to the maternal side of the uterine tissues during pregnancy, supporting the idea that fetal signals can be delivered via exosomes

Association of Neighborhood Socioeconomic Disadvantage and Postpartum Readmission.

We assessed whether neighborhood socioeconomic disadvantage, as measured by the Area Deprivation Index (ADI), was associated with an increased risk of postpartum readmission. This is a secondary analysis from nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be), a prospective cohort of nulliparous pregnant individuals from 2010 to 2013. The exposure was the ADI in quartiles, and the outcome was postpartum readmission; Poisson regression was used. Among 9,061 assessed individuals, 154 (1.7%) were readmitted postpartum within 2 weeks of delivery. Individuals living with the most neighborhood deprivation (ADI quartile 4) were at increased risk of postpartum readmission compared with those living with the lowest neighborhood deprivation (ADI quartile 1) (adjusted risk ratio 1.80, 95% CI 1.11-2.93). Measures of community-level adverse social determinants of health, such as the ADI, may inform postpartum care after delivery discharge

Tobacco Use, Exposure to Secondhand Smoke, and Cessation Counseling Among Health Professions Students: Greek Data from the Global Health Professions Student Survey (GHPSS).

We conducted the GHPSS (Global Health Professions Student Survey) to obtain information regarding health profession students’ smoking habits and perceptions, exposure to secondhand smoke (SHS) as well as level of knowledge and training on tobacco use and smoking cessation counseling. GHPSS is a survey for third-year students in the following fields: health visitors, dentistry, medicine, nursing and/or pharmacy. The highest tobacco use prevalence rate and exposure to SHS were recorded among health visitor students with 46.4% and 33.3% respectively. The majority of the respondents believed that their profession serves as a role model for their patients. Formal training on cessation counseling ranged between 10.7% for health visitor students to 22.4% for nursing students. The relatively high percentage of health profession students who currently smoke and the alarmingly high percentage of those exposed to SHS indicate lack of concerted efforts for implementation and effective enforcement of the anti-tobacco policy measures. Despite its significance, formal training on cessation counseling for students is strikingly low. These results indicate the urgent need to train health professional students on tobacco cessation counseling and educate them on the dangers of tobacco use, SHS and the positively influential role they can play to affect their patients’ smoking habits

Adjunctive Azithromycin Prophylaxis for Cesarean Delivery

The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section