Background Preterm delivery remains the leading cause of perinatal mortality. Risk factors and biomarkers have traditionally failed to identify the majority of preterm deliveries. Objective To ...develop and validate a mass spectrometry–based serum test to predict spontaneous preterm delivery in asymptomatic pregnant women. Study Design A total of 5501 pregnant women were enrolled between 170/7 and 286/7 weeks gestational age in the prospective Proteomic Assessment of Preterm Risk study at 11 sites in the United States between 2011 and 2013. Maternal blood was collected at enrollment and outcomes collected following delivery. Maternal serum was processed by a proteomic workflow, and proteins were quantified by multiple reaction monitoring mass spectrometry. The discovery and verification process identified 2 serum proteins, insulin-like growth factor–binding protein 4 (IBP4) and sex hormone–binding globulin (SHBG), as predictors of spontaneous preterm delivery. We evaluated a predictor using the log ratio of the measures of IBP4 and SHBG (IBP4/SHBG) in a clinical validation study to classify spontaneous preterm delivery cases (<370/7 weeks gestational age) in a nested case-control cohort different from subjects used in discovery and verification. Strict blinding and independent statistical analyses were employed. Results The predictor had an area under the receiver operating characteristic curve value of 0.75 and sensitivity and specificity of 0.75 and 0.74, respectively. The IBP4/SHBG predictor at this sensitivity and specificity had an odds ratio of 5.04 for spontaneous preterm delivery. Accuracy of the IBP4/SHBG predictor increased using earlier case-vs-control gestational age cutoffs (eg, <350/7 vs ≥350/7 weeks gestational age). Importantly, higher-risk subjects defined by the IBP4/SHBG predictor score generally gave birth earlier than lower-risk subjects. Conclusion A serum-based molecular predictor identifies asymptomatic pregnant women at risk of spontaneous preterm delivery, which may provide utility in identifying women at risk at an early stage of pregnancy to allow for clinical intervention. This early detection would guide enhanced levels of care and accelerate development of clinical strategies to prevent preterm delivery.
Abstract Background Experimental and epidemiologic data suggest that among non-pregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly ...complain of poor sleep, few studies have objectively evaluated the quality of sleep in pregnancy or have explored the relationship between sleep disturbances and maternal and perinatal outcomes. Objectives Our objective was to examine the relationship between objectively assessed sleep duration, timing and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. Study Design This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks’ gestation. They were asked to wear a wrist actigraphy monitor and to complete a daily sleep log for a seven consecutive-day period. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (< 7 hours/night), late sleep midpoint (midpoint between sleep onset and sleep offset > 5 AM), and top quartile of minutes of wake time after sleep onset (WASO) and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes (GDM). Chi-square tests were used to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and GDM. For associations that were significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. Results Nine-hundred and one eligible women consented to participate. Of these women 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of GDM (OR 2.24, 95% CI 1.11, 4.53; OR 2.58, 95% CI 1.24, 5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with GDM remained significant (aOR 2.06, 95% CI 1.01, 4.19; aOR 2.37, 95% CI 1.13, 4.97, respectively). Additionally, after adjusting separately for age, BMI and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with GDM. No associations were demonstrated between the sleep quality measures (WASO, sleep fragmentation) and hypertensive disorders or GDM. Conclusions Our results demonstrate a relationship between short sleep duration and later sleep midpoint with GDM. Our data suggest independent contributions of these two sleep characteristics to the risk for GDM in nulliparous women.
Objective The primary aim of the “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” is to determine maternal characteristics, which include genetic, physiologic response to pregnancy, ...and environmental factors that predict adverse pregnancy outcomes. Study Design Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at 3 study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine, cervicovaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending at <37+0 weeks’ gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction. Results We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported. Conclusion The “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” cohort study methods and procedures can help investigators when they plan future projects.
Background The Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network previously demonstrated an association between stillbirth and ...maternal marijuana use as defined by the presence of tetrahydrocannabinol in the umbilical cord homogenate. However, the relationship between marijuana use and perinatal complications in live births is uncertain. Objective Our aim was to examine if maternal marijuana use is associated with increased odds of adverse pregnancy outcomes and neonatal morbidity among live-born controls in the Stillbirth Collaborative Research Network cohort. Study Design We conducted secondary analysis of singleton, live-born controls in the Stillbirth Collaborative Research Network data set. Marijuana use was measured by self-report and/or the presence of tetrahydrocannabinol in umbilical cord homogenate. Tobacco use was measured by self-report and/or presence of any cotinine in maternal serum. Adverse pregnancy outcome was a composite of small for gestational age, spontaneous preterm birth resulting from preterm labor with or without intact membranes, and hypertensive disorders of pregnancy. Neonatal morbidity included neonatal intensive care unit admission and composite neonatal morbidity (pulmonary morbidity, necrotizing enterocolitis, seizures, retinopathy of prematurity, infection morbidity, anemia requiring blood transfusion, neonatal surgery, hyperbilirubinemia, neurological morbidity, or death prior to hospital discharge). Effect of maternal marijuana use on the probability of an adverse outcome was estimated using weighted methodology to account for oversampling in the original study. tetrahydrocannabinol cord homogenate analysis was performed in the subset of women for whom biospecimens were available. Comparisons using logistic modeling, χ2 , and t tests were weighted to account for oversampling of preterm births and non-Hispanic blacks. Results are reported as weighted percent and unweighted frequencies. Results Maternal marijuana use was identified in 2.7% (unweighted frequency 48/1610) of live births. Use was self-reported by 1.6% (34/1610) and detected by tetrahydrocannabinol in cord homogenate for 1.9% (17/897), n = 3 overlapping. Rate of tobacco use was 12.9% (217/1610), with 10.7% (167/1607) by self-report and 9.5% (141/1313) by serum cotinine. The composite adverse pregnancy outcome was not significantly increased in women with marijuana use compared to nonusers (31.2% vs 21.2%; P = .14). After adjustment for tobacco, clinical, and socioeconomic factors, marijuana use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio, 1.29; 95% confidence interval, 0.56–2.96). Similarly, among women with umbilical cord homogenate and serum cotinine data (n = 765), marijuana use was not associated with adverse pregnancy outcomes (adjusted odds ratio, 1.02; 95% confidence interval, 0.18–5.66). Neonatal intensive care unit admission rates were not statistically different between groups (16.9% users vs 9.5% nonusers, P = .12). Composite neonatal morbidity or death was more frequent among neonates of mothers with marijuana use compared to nonusers (14.1% vs 4.5%; P = .002). In univariate comparisons, the components of the composite outcome that were more frequent in neonates of marijuana users were infection morbidity (9.8% vs 2.4%; P < .001) and neurologic morbidity (1.4% vs 0.3%; P = .002). After adjustment for tobacco, race, and other illicit drug use, marijuana use was still associated with composite neonatal morbidity or death (adjusted odds ratio, 3.11; 95% confidence interval, 1.40–6.91). Conclusion Maternal marijuana use was not associated with a composite of small for gestational age, spontaneous preterm birth, or hypertensive disorders of pregnancy. However, it was associated with an increased risk of neonatal morbidity.
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. Massive transfusion protocols involve the early utilization of blood products and limit the traditional approach of early massive crystalloid-based resuscitation. The evidence behind hemostatic resuscitation has changed in the last few years, and debate is ongoing regarding optimal transfusion strategies. The use of tranexamic acid, fibrinogen concentrates, and prothrombin complex concentrates has emerged as new potential alternative treatment strategies with improved safety profiles.
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. Study Design Chorioamniotic membranes were collected from normal term deliveries; group 1: term labor and group 2: term, not in labor. Senescence-related morphologic changes were determined by transmission electron microscopy and biochemical changes were studied by senescence-associated (SA) β-galactosidase staining. Amniotic fluid samples collected from both term labor and term not in labor were analyzed for 14 SA secretory phenotype (SASP) markers. Results Morphologic evidence of cellular senescence (enlarged cells and organelles) and a higher number of SA β-galactosidase-stained amnion and chorion cells were observed in chorioamniotic membranes obtained from women in labor at term, when compared to term not in labor. The concentration of proinflammatory SASP markers (granulocyte macrophage colony-stimulating factor, interleukin-6 and -8) was significantly higher in the amniotic fluid of women in labor at term than women not in labor. In contrast, SASP factors that protect against cell death (eotaxin-1, soluble Fas ligand, osteoprotegerin, and intercellular adhesion molecule-1) were significantly lower in the amniotic fluid samples from term labor. Conclusion Morphologic and biochemical features of senescence were more frequent in chorioamniotic membranes from women who experienced term labor. Senescence of chorioamniotic membranes were also associated with amniotic fluid SASP markers.
Background Consumption of fructose-rich diets in the United States is on the rise and thought to be associated with obesity and cardiometabolic diseases. Objective We sought to determine the effects ...of antenatal exposure to high-fructose diet on offspring’s development of metabolic syndrome–like phenotype and other cardiovascular disease risk factors later in life. Study Design Pregnant C57BL/6J dams were randomly allocated to fructose solution (10% wt/vol, n = 10) or water (n = 10) as the only drinking fluid from day 1 of pregnancy until delivery. After weaning, pups were started on regular chow, and evaluated at 1 year of life. We measured percent visceral adipose tissue and liver fat infiltrates using computed tomography, and blood pressure using CODA nonivasive monitor. Intraperitoneal glucose tolerance testing with corresponding insulin concentrations were obtained. Serum concentrations of glucose, insulin, triglycerides, total cholesterol, leptin, and adiponectin were measured in duplicate using standardized assays. Fasting homeostatic model assessment was also calculated to assess insulin resistance. P values <.05 were considered statistically significant. Results Maternal weight, pup number, and average weight at birth were similar between the 2 groups. Male and female fructose group offspring had higher peak glucose and area under the intraperitoneal glucose tolerance testing curve compared with control, and higher mean arterial pressure compared to control. Female fructose group offspring were heavier and had higher percent visceral adipose tissue, liver fat infiltrates, homeostatic model assessment of insulin resistance scores, insulin area under the intraperitoneal glucose tolerance testing curve, and serum concentrations of leptin, and lower concentrations of adiponectin compared to female control offspring. No significant differences in these parameters were noted in male offspring. Serum concentrations of triglycerides or total cholesterol were not different between the 2 groups for either gender. Conclusion Maternal intake of high fructose leads to fetal programming of adult obesity, hypertension, and metabolic dysfunction, all risk factors for cardiovascular disease. This fetal programming is more pronounced in female offspring. Limiting intake of high fructose–enriched diets in pregnancy may have significant impact on long-term health.
Abstract Background The significance of periconceptional nutrition for optimizing offspring and maternal health and reducing social inequalities warrants greater understanding of diet quality among ...US women. Objective Our objective was to evaluate racial or ethnic and education inequalities in periconceptional diet quality and sources of energy and micronutrients. Design Cross-sectional analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort. Participants and setting Nulliparous women (N=7,511) were enrolled across eight US medical centers from 2010 to 2013. Main outcome measures A semiquantitative food frequency questionnaire assessing usual dietary intake during the 3 months around conception was self-administered during the first trimester. Diet quality, measured using the Healthy Eating Index-2010 (HEI-2010), and sources of energy and micronutrients were the outcomes. Statistical analyses Differences in diet quality were tested across maternal racial or ethnic and education groups using F tests associated with analysis of variance and χ2 tests. Results HEI-2010 score increased with higher education, but the increase among non-Hispanic black women was smaller than among non-Hispanic whites and Hispanics (interaction P value <0.0001). For all groups, average scores for HEI-2010 components were below recommendations. Top sources of energy were sugar-sweetened beverages, pasta dishes, and grain desserts, but sources varied by race or ethnicity and education. Approximately 34% of energy consumed was from empty calories (the sum of energy from added sugars, solid fats, and alcohol beyond moderate levels). The primary sources of iron, folate, and vitamin C were juices and enriched breads. Conclusions Diet quality is suboptimal around conception, particularly among women who are non-Hispanic black, Hispanic, or who had less than a college degree. Diet quality could be improved by substituting intakes of refined grains and foods empty in calories with vegetables, peas and beans (legumes), seafood, and whole grains.
Putting the “M” back in maternal–fetal medicine D'Alton, Mary E., MD; Bonanno, Clarissa A., MD; Berkowitz, Richard L., MD ...
American journal of obstetrics and gynecology,
06/2013, Volume:
208, Issue:
6
Journal Article
Peer reviewed
Although maternal death remains rare in the United States, the rate has not decreased for 3 decades. The rate of severe maternal morbidity, a more prevalent problem, is also rising. Rise in maternal ...age, in rates of obesity, and in cesarean deliveries as well as more pregnant women with chronic medical conditions all contribute to maternal mortality and morbidity in the United States. We believe it is the responsibility of maternal-fetal medicine (MFM) subspecialists to lead a national effort to decrease maternal mortality and morbidity. In doing so, we hope to reestablish the vital role of MFM subspecialists to take the lead in the performance and coordination of care in complicated obstetrical cases. This article will summarize our initial recommendations to enhance MFM education and training, to establish national standards to improve maternal care and management, and to address critical research gaps in maternal medicine.
Given that practice variation exists in the frequency and performance of ultrasound and magnetic resonance imaging in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and ...Human Development hosted a workshop to address indications for ultrasound and magnetic resonance imaging in pregnancy, to discuss when and how often these studies should be performed, to consider recommendations for optimizing yield and cost-effectiveness and to identify research opportunities. This article is the executive summary of the workshop.
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