Interpreting a randomized trial report: evidence-based practice for the clinician.

The purpose of this article is to present a structured approach to help the reader with the objective interpretation of published randomized clinical trials. This process will promote an organized and critical appraisal of scientific evidence, which we believe to be an essential step prior to the introduction of published scientific findings into clinical practice. The reason to personally scrutinize and critically assess published reports is that the process of peer review is by no means perfect and methodological flaws can be uncovered, even in articles published in prestigious journals.

Early versus Late Feeding after Cesarean Delivery: A Randomized Controlled Trial.

Objective: This study aims to evaluate whether early feeding after cesarean delivery (CD) shortens the time to pass flatus and bowel movement.

Methods: Women at term undergoing CD were randomly assigned to start oral intake either within 6 hours (early feeding) or after 12 hours (late feeding) from surgery completion. Women with preeclampsia, or requiring emergent CD, additional bowel surgery, or the use of general anesthesia were excluded.

Alterations to the maternal circulating proteome after preeclampsia.

Objective: The long-term maternal cardiovascular and metabolic implications associated with preeclampsia (PE) include risk of hypertension, heart disease, and metabolic syndrome. The objective of this study was to investigate if a recent history of PE was associated with detectable alterations in the circulating maternal proteome.

Study Design: Six-month postpartum plasma from women with a history of PE (n = 12) and women with uncomplicated obstetrical history (n = 12) were used for analysis.

Telomere Fragment Induced Amnion Cell Senescence: A Contributor to Parturition?

Oxidative stress (OS)-induced senescence of the amniochorion has been associated with parturition at term. We investigated whether telomere fragments shed into the amniotic fluid (AF) correlated with labor status and tested if exogenous telomere fragments (T-oligos) could induce human and murine amnion cell senescence. In a cross-sectional clinical study, AF telomere fragment concentrations quantitated by a validated real-time PCR assay were higher in women in labor at term compared to those not in labor.

Severe placental abruption: clinical definition and associations with maternal complications.

Background: Placental abruption traditionally is defined as the premature separation of the implanted placenta before the delivery of the fetus. The existing clinical criteria of severity rely exclusively on fetal (fetal distress or fetal death) and maternal complications without consideration of neonatal or preterm delivery-related complications. However, two-thirds of abruption cases are accompanied by fetal or neonatal complications, including preterm delivery.

An update on the use of massive transfusion protocols in obstetrics.

Obstetrical hemorrhage remains a leading cause of maternal mortality worldwide. New concepts involving the pathophysiology of hemorrhage have been described and include early activation of both the protein C and fibrinolytic pathways. New strategies in hemorrhage treatment include the use of hemostatic resuscitation, although the optimal ratio to administer the various blood products is still unknown.

A Randomized Trial of Intrapartum Fetal ECG ST-Segment Analysis.

Background: It is unclear whether using fetal electrocardiographic (ECG) ST-segment analysis as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring modifies intrapartum and neonatal outcomes.

Methods: We performed a multicenter trial in which women with a singleton fetus who were attempting vaginal delivery at more than 36 weeks of gestation and who had cervical dilation of 2 to 7 cm were randomly assigned to "open" or "masked" monitoring with fetal ST-segment analysis. The masked system functioned as a normal fetal heart-rate monitor.

Environmental Pollutant Polybrominated Diphenyl Ether, a Flame Retardant, Induces Primary Amnion Cell Senescence.

Objective: Polybrominated diphenyl ethers (PBDEs) are documented to increase the risk for spontaneous preterm birth (PTB). We hypothesize that PBDEs cause oxidative stress (OS) that leads to fetal cell senescence and inflammation associated with PTB.

Methods: Primary amnion epithelial cells (n = 5) isolated from term, not in labor pregnancies, were exposed to PBDE congeners 47 and 99 (each 5 μM).

Serious maternal complications after early preterm delivery (24-33 weeks' gestation).

Objective: We sought to describe the prevalence of serious maternal complications following early preterm birth by gestational age (GA), delivery route, and type of cesarean incision.

Study Design: Trained personnel abstracted data from maternal and neonatal charts for all deliveries on randomly selected days representing one third of deliveries across 25 US hospitals over 3 years (n = 115,502). All women delivering nonanomalous singletons between 23-33 weeks' gestation were included.

Obesity Risk Knowledge, Weight Misperception, and Diet and Health-Related Attitudes among Women Intending to Become Pregnant.

Objective: Our aim was to evaluate obesity risk knowledge, weight misperception, and diet and health-related attitudes among women intending to become pregnant compared to those not intending to become pregnant.

Design: We conducted a cross-sectional survey of health behaviors, including obesity risk knowledge, weight misperception, and diet and health-related attitudes among women (aged 16 to 40 years) attending reproductive health clinics in southeast Texas. Data were collected through self-administered questionnaires and chart review.

Timing of treatment initiation for mild gestational diabetes mellitus and perinatal outcomes.

Objective: The purpose of this study was to examine the association between gestational age (GA) at the time of treatment initiation for gestational diabetes mellitus (GDM) and maternal and perinatal outcomes.

Study Design: We conducted a secondary analysis of a multicenter randomized treatment trial of mild GDM in which women with mild GDM were assigned randomly to treatment vs usual care. The primary outcome of the original trial, as well as this analysis, was a composite perinatal adverse outcome that included neonatal hypoglycemia, hyperbilirubinemia, hyperinsulinemia, and perinatal death.

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms.

Objective: We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB.

Study Design: We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.

Chorioamniotic membrane senescence: a signal for parturition?

Objective: Senescence is an important biological phenomenon involved in both physiologic and pathologic processes. We propose that chorioamniotic membrane senescence is a mechanism associated with human parturition. The present study was conducted to explore the association between senescence and normal term parturition by examining the morphologic and biochemical evidences in chorioamniotic membranes.

Screening of lysyl oxidase (LOX) and lysyl oxidase like (LOXL) enzyme expression and activity in preterm prelabor rupture of fetal membranes.

Objective: Lysyl oxidase (LOX) and LOX like enzymes (LOXL1-4) physiologically remodel extracellular matrix and pathologically contribute to cellular senescence under oxidative stress (OS). We characterized LOX and LOXL expressions and activity in human fetal membranes.

Methods: Human fetal membranes from women with uncomplicated pregnancies at term, preterm birth with intact membranes (PTB) or preterm prelabor rupture of membranes (pPROM), and in vitro fetal membranes stimulated with water-soluble cigarette smoke extract (CSE), an OS inducer, were analyzed by real-time PCR and immunohistochemistry for LOX and LOXL (1-4) expression and localization.

Placental telomere shortening in stillbirth: a sign of premature senescence?

Objective: The objective of this study is to investigate placental telomere shortening in unexplained stillbirths (SBs) as an indication of premature senescence.

Methods: Placentas were collected from 42 unexplained SB (>22 weeks), 43 term and 15 preterm live births, at the Policlinico Hospital of Modena (Italy). DNA extracted from placentae was studied for telomere length by real time PCR.

Aging of intrauterine tissues in spontaneous preterm birth and preterm premature rupture of the membranes: A systematic review of the literature.

Background: Many adverse pregnancy outcomes (APOs), including spontaneous preterm birth (PTB), are associated with placental dysfunction. Recent clinical and experimental evidences suggest that premature aging of the placenta may be involved in these events. Although placental aging is a well-known concept, the mechanisms of aging during normal pregnancy and premature aging in APOs are still unclear.

Racial and ethnic disparities in maternal morbidity and obstetric care.

Objective: To evaluate whether racial and ethnic disparities exist in obstetric care and adverse outcomes.

Methods: We analyzed data from a cohort of women who delivered at 25 hospitals across the United States over a 3-year period. Race and ethnicity was categorized as non-Hispanic white, non-Hispanic black, Hispanic, or Asian.

NuMoM2b Sleep-Disordered Breathing study: objectives and methods.

Objective: The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing during pregnancy is a risk factor for adverse pregnancy outcomes.

Study Design: NuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations that was conducted across 8 sites with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing.

Morbidly adherent placenta treatments and outcomes.

Objective: To describe recent maternal and neonatal delivery outcomes among women with a morbidly adherent placenta in major centers across the United States.

Methods: This study reviewed a cohort of 115,502 women and their neonates born in 25 hospitals in the United States between March 2008 and February 2011 from the Assessment of Perinatal EXcellence data set. All cases of morbidly adherent placenta were identified.

The Effect of Simvastatin on Infection-Induced Inflammatory Response of Human Fetal Membranes.

Problem: Inflammatory cytokines and matrix metalloproteinases (MMPs) contribute to preterm labor pathophysiology. The objective of this study was to test anti-inflammatory properties of simvastatin in human fetal membranes exposed to lipopolysaccharide (LPS).

Method Of Study: Normal term human fetal membrane explants (n = 11) were allocated to one of the six study groups: control, LPS only (100 ng/mL), simvastatin only (125 ng/mL), simvastatin given 6 hrs prior to LPS (S-L), simvastatin given 6 hrs post-LPS (L-S), and simvastatin and LPS given simultaneously (L+S).

The phenotype of spontaneous preterm birth: application of a clinical phenotyping tool.

Objective: Spontaneous preterm birth (SPTB) is a complex condition that is likely a final common pathway with multiple possible causes. We hypothesized that a comprehensive classification system appropriately could group women with similar STPB causes and could provide an explanation, at least in part, for the disparities in SPTB that are associated with race and gestational age at delivery.

Study Design: This was a planned analysis of a multicenter, prospective study of singleton SPTBs.

Fetal DNA methylation of autism spectrum disorders candidate genes: association with spontaneous preterm birth.

Objective: Autism spectrum disorder (ASD) is associated with preterm birth (PTB), although the reason underlying this relationship is still unclear. Our objective was to examine DNA methylation patterns of 4 ASD candidate genes in human fetal membranes from spontaneous PTB and uncomplicated term birth.

Study Design: A literature search for genes that have been implicated in ASD yielded 14 candidate genes (OXTR, SHANK3, BCL2, RORA, EN2, RELN, MECP2, AUTS2, NLGN3, NRXN1, SLC6A4, UBE3A, GABA, AFF2) that were epigenetically modified in relation to ASD.

The association of stillbirth with depressive symptoms 6-36 months post-delivery.

Background: Stillbirths (≥ 20 weeks' gestation), which account for about 1 in 200 US pregnancies, may grieve parents deeply. Unresolved grief may lead to persistent depression.

Methods: We compared depressive symptoms in 2009 (6-36 months after index delivery) among consenting women in the Stillbirth Collaborative Research Network's population-based case-control study conducted 2006-08 (n = 275 who delivered a stillbirth and n = 522 who delivered a healthy livebirth (excluding livebirths < 37 weeks, infants who had been admitted to a neonatal intensive care unit or who died).