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We sought to determine if pyelonephritis and preterm delivery occur more frequently among pregnant women with polymicrobial growth from screening urine culture than among women with negative urine culture. A retrospective cohort study was performed. Three hundred eighty pregnant women with greater than 100,000 colony-forming units per milliliter of polymicrobial growth from urine culture performed at less than 20 weeks of pregnancy were compared with 375 women with negative urine culture. Admissions for pyelonephritis were identified from discharge records. Gestational age at delivery was determined from a research registry. Frequency of pyelonephritis and preterm delivery did not differ between the two groups. Frequencies of pyelonephritis were 0.3% and 0% in women with polymicrobial and negative urine culture, respectively ( P = 0.32). Frequencies of preterm delivery were 16.8% and 16% ( P = 0.76). Among those with repeat urine cultures, 4.6% in the polymicrobial group and 2.4% of those in the negative initial urine culture group had a positive culture later in the pregnancy ( P = 0.21). There is no association between polymicrobial growth from screening urine culture and pyelonephritis or preterm delivery.

Providers occasionally screen women thought to be at particularly increased risk of gestational diabetes mellitus (GDM) with a first- or second-trimester ("early") glucose tolerance test (GTT). We sought to describe how the frequency of abnormal early GTT varies by indication for testing. This is a retrospective cohort study of women receiving prenatal care in our clinic who underwent a 50-g GTT at less than 24 weeks between 2003 and 2006. Three hundred five women received an early GTT. The most common indications for early screening were obesity (53%), family history of diabetes (15%), prior history of GDM (10%), and multifetal gestation (5%). The frequency of abnormal testing in patients with multifetal gestations and a personal history of GDM was higher than in those undergoing early testing because of obesity. The frequency of abnormal early GTT varies by indication for testing. These data may be used in the allocation of health care resources.

Background: Poor maternal folate status has been associated with an increased risk of preterm birth. However, major gaps remain in our understanding of how individual folate species relate to preterm birth. Objective: Our objective was to assess the association between maternal folate status as measured by 5-methyltetrahydrofolate (5MeTHF), 5-formyltetrahydrofolate (5FoTHF), and folic acid concentrations, which are the 3 primary folate species in serum, and the risk of preterm birth and spontaneous preterm birth (sPTB). Design: A cohort of 313 pregnant women who received care at resident antepartum clinics at Magee-Womens Hospital (Pittsburgh, PA) (2003–2007) was enrolled at

Evidence suggests that release of oxytocin in the nucleus tractus solitarius (NTS) of the hindbrain from descending projections that originate in the paraventricular nucleus can inhibit food intake by amplifying the satiety response to cholecystokinin (CCK). To further evaluate this mechanism in rats, we used a novel cytotoxin, saporin conjugated to oxytocin (OXY-SAP), a compound designed to destroy cells that express oxytocin receptors (OXYr). OXY-SAP was injected directly into the NTS to lesion neurons that express OXYr and that are implicated in potentiating CCK’s satiety effects. The control consisted of injection of saporin conjugated to a nonsense peptide. We found that OXY-SAP was cytotoxic to human uterine smooth muscle cells in vitro, demonstrating that OXY-SAP can lesion cells that express OXYr. Using laser capture microdissection and real-time quantitative PCR, we demonstrated that OXYr mRNA levels were reduced in the NTS after OXY-SAP administration. Moreover, we found that OXY-SAP attenuated the efficacy of CCK-8 to reduce food intake and blocked the actions of an OXYr antagonist to stimulate food intake. The findings suggest that OXY-SAP is an effective neurotoxin for in vivo elimination of cells that express OXYr and is potentially useful for studies to analyze central nervous system mechanisms that involve the action of oxytocin on food intake and other physiological processes.

Maternal vitamin D deficiency has been associated with numerous adverse health outcomes, but its association with fetal growth restriction remains uncertain. We sought to elucidate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations in early pregnancy and the risk of small-for-gestational age birth (SGA) and explore the association between maternal single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene and the risk of SGA. We conducted a nested case-control study of nulliparous pregnant women with singleton pregnancies who delivered SGA infants (n = 77 white and n = 34 black) or non-SGA infants (n = 196 white and n = 105 black). Women were followed from 75 nmol/L were 7.5 (1.8, 31.9) and 2.1 (1.2, 3.8), respectively. There was no relation between 25(OH)D and SGA risk among black mothers. One SNP in the VDR gene among white women and 3 SNP in black women were significantly associated with SGA. Our results suggest that vitamin D has a complex relation with fetal growth that may vary by race.

In the United States, significant, intractable disparities exist in rates of major pregnancy outcomes between non-Hispanic black and non-Hispanic white women. A previously unexplored candidate influence on the black-white disparity in adverse birth outcomes is maternal vitamin D status. This review summarizes the evidence relating maternal vitamin D to preeclampsia, spontaneous preterm birth, gestational diabetes, and fetal growth restriction, and addresses gaps in our understanding of the contribution of vitamin D to the intractable black-white disparity in these conditions. The literature reviewed highlights strong biologic plausibility of role for vitamin D in the pathophysiology of these poor pregnancy outcomes. Data also suggest that maternal vitamin D deficiency may increase the risk of preeclampsia and fetal growth restriction. Less research has been done in support of relations with spontaneous preterm birth and gestational diabetes, and fetal and infant survival have rarely been studied. Few trials of vitamin D supplementation have been conducted in pregnant women with adequate power to test effects on birth outcomes. Importantly, black pregnant women have rarely been studied in vitamin D-birth outcomes research. Although vitamin D is a promising candidate influence on black-white disparities in preeclampsia, spontaneous preterm birth, fetal growth restriction, and gestational diabetes, these associations require further study in large samples of black US women. Because vitamin D deficiency is widespread and black-white disparities in pregnancy outcomes and infant survival have been resistant to previous interventions, research to test vitamin D as a causal factor is of major public health significance.ObstetriciansGynecologist, Family Physicians.After completion of this educational activity, the reader will be able to appreciate risk factors for inadequate vitamin D status. Understand the basic aspects of vitamin D metabolism. Become aware of recent literature linking inadequate vitamin D status and adverse pregnancy outcomes such as preeclampsia and preterm birth.

To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke.DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile462Val AAAG/GG), GSTT1(del), and CYP2A6 (Lys160His TA). Modification of the association between smoking and outcome by genotype was evaluated. Outcomes included birth weight, pregnancy loss, preterm birth, small for gestational age, and a composite outcome composed of the latter four components plus abruption.No interaction between maternal or fetal genotype of any of the polymorphisms and smoking could be demonstrated. In contrast, the association of smoking with gestational age-adjusted birth weight (birth weight ratio) was modified by fetal GSTT1 genotype (P for interaction=.02). Fetuses with GSTT1(del) had a mean birth weight reduction among smokers of 262 g (P=.01), whereas in fetuses without the GSTT1(del) the effect of tobacco exposure was nonsignificant (mean reduction 87 g, P=.16). After adjusting for confounding, results were similar.Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age-corrected birth weight.

Allelic variants in vitamin D metabolism genes may increase the risk of preeclampsia, but few studies have systematically tested this hypothesis. Our objective was to evaluate the relationship between maternal allelic variants in three vitamin D metabolism genes and risk of preeclampsia. Samples were from two case‐control studies of pregnant women who delivered in Pittsburgh, PA from 1999 to 2010 and twelve recruiting sites across the United States from 1959 to 1965. Single‐nucleotide polymorphisms (SNPs) were genotyped 50 kilobases up‐ and down‐stream in three genes (VDR,GC, and CYP27B1) in the samples from both studies, for a total of 744 preeclampsia cases and 2411 controls. Using multivariable logistic regression, we estimated the associations between allelic variation in each locus and preeclampsia risk by maternal race and study. Meta‐analysis was used to estimate the association across race‐study groups for each SNP. Minor allele of a noncoding region of the VDR gene was significantly associated with preeclampsia risk, which was verified in the meta‐analysis [odds ratio (OR), 95% confidence intervals (CI)] after adjusting for multiple comparisons [rs12831006:1.5 (1.2, 2.0), P

ObjectiveTo assess the adequacy of periconceptional intake of key micronutrients for perinatal health in relation to regular cereal consumption of pregnant women.Design, setting and subjectsLow-income pregnant women (n596) in Pittsburgh, Pennsylvania, USA, who enrolled in a cohort study at ResultsAbout 31 % of the women regularly consumed cereal. After adjusting for energy intake, race/ethnicity, marital status, breakfast consumption and supplement use, cereal eaters had significantly higher intakes of folate, Fe, Zn, Ca, fibre and vitamins A, C, D and E (allP< 0·01) and were approximately two to six times more likely to have intakes in the highest third of the distribution for folate, Fe, Zn, Ca, vitamins A and D, and fibre (allP< 0·01) than cereal non-eaters. Cereal consumption was also associated with reductions of 65–90 % in the risk of nutrient inadequacies compared with non-consumption (allP< 0·01).ConclusionsEncouraging cereal consumption may be a simple, safe and inexpensive nutrition intervention that could optimize periconceptional intake for successful placental and fetal development.

Bacterial vaginosis (BV) is a highly prevalent vaginal infection that is associated with adverse pregnancy outcomes. Vitamin D exerts an influence on the immune system and may play a role in BV. The objective of this study was to examine the association between maternal vitamin D status and the prevalence of BV in early pregnancy. Women (n = 469) enrolled in a pregnancy cohort study at 80 nmol/L. There was a dose-response association between 25(OH)D and the prevalence of BV. The prevalence declined as 25(OH)D increased to 80 nmol/L, then reached a plateau. Compared with a serum 25(OH)D concentration of 75 nmol/L, there were 1.65-fold (95% CI: 1.01, 2.69) and 1.26-fold (1.01, 1.57) increases in the prevalence of BV associated with a serum 25(OH)D concentration of 20 and 50 nmol/L, respectively, after adjustment for race and sexually transmitted diseases. Vitamin D deficiency is associated with BV and may contribute to the strong racial disparity in the prevalence of BV.

To examine the effects that medical staff education and a new process for scheduling inductions had on decreasing inappropriate inductions.At our institution in 2004, guidelines were developed and shared with the medical staff and reinforced in 2005. The guidelines for elective induction required patients to have completed 39 weeks of gestation and to have a Bishop score of at least 8 for nulliparas and 6 for multiparas. In 2006, the induction scheduling process was changed and the guidelines were strictly enforced. All scheduled inductions during the same 3-month time period (June through August) in 2004 (n=533) and 2005 (n=454) and during a 13-month period from November 2006 to December 2007 (n=1,806) were compared. Outcomes included elective inductions less than 39 weeks, cesarean birth rate for elective inductions among nulliparas, and the overall induction rate.From 2004-2007, the overall induction rate dropped from 24.9% to 16.6%, a 33% reduction(P.001); the elective induction rate dropped from 9.1% to 6.4%, a 30% reduction (P.001); the percentage of elective inductions before 39 weeks of gestation dropped from 11.8% to 4.3%, a decrease of 64% (P.001); and the frequency of cesarean delivery among nulliparas undergoing elective induction dropped from 34.5% to 13.8%, a decrease of 60%. (P=.01).Medical staff education and the development and enforcement of induction guidelines contributed to a decrease in inappropriate inductions, a lower cesarean birth rate for electively induced nulliparas, and a lower elective and overall induction rate.III.

Preterm birth is a heterogeneous disorder that is responsible for significant neonatal morbidity and mortality. Intrauterine infection is implicated in a significant proportion of preterm birth-particularly in early gestation. Epidemiologic evidence supports a genetic component to infection overall and preterm birth in particular. Furthermore, a number of studies examining genes involved in pathogen recognition and our response to pathogens suggest a genetic susceptibility to infection-mediated preterm birth. On the whole, however, these studies have been difficult to replicate and explain only a small portion of the phenotypic variation in preterm birth. Given this, methodological considerations are emphasized to improve our understanding of the genetic susceptibility to infection-mediated preterm birth.

Preterm birth is a major obstetric problem. An exploration of the season of conception in relation to preterm birth may provide direction in the search for risk factors. We conducted a retrospective cohort study of 82 213 singleton livebirths (20-45 weeks' gestation) to 61,630 women at Magee-Womens Hospital, Pittsburgh, PA, from 1995 to 2005. Conception was estimated based on gestational age determined by best obstetric estimate. Fourier series analysis was used to model seasonal trends. Spontaneous preterm birth at

Spontaneous preterm birth (PTB

Obesity is a risk factor for vitamin D deficiency but this relation has not been studied among pregnant women who must sustain their own vitamin D stores as well as those of their fetuses. Our objective was to assess the effect of prepregnancy BMI on maternal and newborn 25-hydroxyvitamin D [25(OH)D] concentrations. Serum 25(OH)D was measured at 4-21 wk gestation and predelivery in 200 white and 200 black pregnant women and in their neonates cord blood. We used multivariable logistic regression models to assess the independent association between BMI and the odds of vitamin D deficiency [25(OH)D < 50 nmol/L] after adjustment for race/ethnicity season gestational age multivitamin use physical activity and maternal age. Compared with lean women (BMI < 25) pregravid obese women (BMI $30) had lower adjusted mean serum 25(OH)D concentrations at 4-22 wk (56.5 vs. 62.7 nmol/L; P < 0.05) and a higher prevalence vitamin D deficiency (61 vs. 36%; P < 0.01). Vitamin D status of neonates born to obese mothers was poorer than neonates of lean mothers (adjusted mean 50.1 vs. 56.3 nmol/L; P < 0.05). There was a dose-response trend between prepregnancy BMI and vitamin D deficiency. An increase in BMI from 22 to 34 was associated with 2-fold (95% CI: 1.2 3.6) and 2.1-fold (1.2 3.8) increases in the odds of mid-pregnancy and neonatal vitamin D deficiency respectively. The rise in maternal obesity highlights that maternal and newborn vitamin D deficiency will continue to be a serious public health problem until steps are taken to identify and treat low 25(OH)D. (authors)

Current information on the risk of uterine rupture after cesarean delivery has generally compared the risk after trial of labor to that occurring with an elective cesarean delivery without labor. Because antepartum counseling cannot account for whether a woman will develop an indication requiring a repeat cesarean delivery or whether labor will occur before scheduled cesarean delivery, the purpose of this analysis was to provide clinically useful information regarding the risks of uterine rupture and adverse perinatal outcome for women at term with a history of prior cesarean delivery.Women with a term singleton gestation and prior cesarean delivery were studied over 4 years at 19 centers. For this analysis, outcomes from five groups were studied: trial of labor, elective repeat with no labor, elective repeat with labor (women presenting in early labor who subsequently underwent cesarean delivery), indicated repeat with labor, and indicated repeat without labor. All cases of uterine rupture were reviewed centrally to assure accuracy of diagnosis.A total of 39,117 women were studied. In term pregnant women with a prior cesarean delivery, the overall risk for uterine rupture was 0.32% (125 of 39,117), and the overall risk for serious adverse perinatal outcome (stillbirth, hypoxic ischemic encephalopathy, neonatal death) was 106 of 39,049 (0.27%). The uterine rupture risk for indicated repeat cesarean delivery (labor or without labor) was 7 of 6,080 (0.12%); the risk for elective (no indication) repeat cesarean delivery (labor or without labor) was 4 of 17,714 (0.02%). Indicated repeat cesarean delivery increased the risk of uterine rupture by a factor of 5 (odds ratio 5.1, 95% confidence interval 1.49-17.44). In the absence of an indication, the presence of labor also increased the risk of uterine rupture (4 of 2,721 [0.15%] compared with 0 of 14,993, P.01). The highest rate of uterine rupture occurred in women undergoing trial of labor (0.74%, 114 of 15,323).At term, the risk of uterine rupture and adverse perinatal outcome for women with a singleton and prior cesarean delivery is low regardless of mode of delivery, occurring in 3 per 1,000 women. Maternal complications occurred in 3-8% of women within the five delivery groups.

To examine the contribution of variants in fetal and maternal cholesterol metabolism genes in preterm delivery (PTD). A total of 40 single-nucleotide polymorphisms (SNPs) in 16 genes related to cholesterol metabolism were examined for 414 preterm infants (gestational ages 22 to 36 weeks; comprising 305 singletons and 109 twins) and at least 1 parent. Fetal effects were assessed using the transmission disequilibrium test (TDT) for each SNP, followed by a log linear model-based approach to utilize families with missing parental genotypes for those SNPs showing significance under TDT. Genetic variant effects were examined for a role in PTD, gestational age and birth weight. Maternal effects were estimated using a log linear model-based approach. Among singleton gestations, suggestive association (P

Summary Preterm birth (PTB) is a significant neonatal health problem that is more common in African-Americans (AA) than in European-Americans (EA). Part of this disparity is likely to result from the differing genetic architectures of EA and AA. To begin assessing the role of these differences, patterns of genetic variation in two previously proposed candidate genes, encoding interleukin 6 (IL6) and its receptor (IL6R), were analyzed in mothers and fetuses from 496 EA birth-events (149 cases and 347 controls) and 397 birth-events in AA (76 cases and 321 controls). IL-6 levels in amniotic fluid (AF) samples were determined in a subset of these pregnancies. Case-control comparisons revealed a single SNP in IL6R associated with PTB (p=0.04 for allelic and p=0.05 for genotype association). In addition, all of the SNPs studied showed significant frequency differences between AA and EA in at least one comparison, significantly in excess of that expected from general population databases. Higher IL-6 concentrations were associated with the IL6 SNP -661 in EA preterm samples (p=0.0056), and this result seems to be driven by microbial invasion of the amniotic cavity, indicating a gene by infection interaction. These findings indicate that, as a function of IL6 genotype, EA and AA women respond differently to infection with respect to their expression of IL-6. Our data support differential genetic control of levels of IL-6 in amniotic fluid between EA and AA.

The purpose of this study was to describe the fetal and newborn safety profile of prolonged indomethacin treatment during pregnancy. A retrospective cohort of 124 pregnant women treated with indomethacin was used to assess the outcomes of oligohydramnios, constriction of the ductus arteriosus, and composite neonatal morbidity. Eight patients (6.5%) developed ductal constriction and nine patients (7.3%) developed oligohydramnios. Composite morbidity occurred in 36 neonates (29%). Ductal constriction, oligohydramnios, and composite morbidity were not associated with duration of therapy, gestational age at start or stop of therapy, time between dosing and delivery, or dose regimen. Prolonged indomethacin therapy rarely is associated with ductal constriction and oligohydramnios.

The mean infant birth weight in the United States increased for decades, but it might now be decreasing. Given race disparities in fetal growth, we explored race-specific trends in birth weight at Magee-Womens Hospital, Pittsburgh, Pennsylvania, from 1997 to 2011. Among singleton births delivered at 37-41 weeks (n = 70,607), we evaluated the proportions who were small for gestational age and large for gestational age and changes in mean birth weights over time. Results were stratified by maternal race/ethnicity. Since 1997, the number of infants born small for their gestational ages increased (8.7%-9.9%), whereas the number born large for their gestational ages decreased (8.9%-7.7%). After adjustment for gestational week at birth, maternal characteristics, and pregnancy conditions, birth weight decreased by 2.20 g per year (P0.0001). Decreases were greater for spontaneous births. Reductions were significantly greater in infants born to African-American women than in those born to white women (-3.78 vs. -1.88 per year; P for interaction = 0.010). Quantile regression models indicated that birth weight decreased across the entire distribution, but reductions among infants born to African-American women were limited to those in the upper quartile after accounting for maternal factors. Limiting the analysis to low-risk women eliminated birth weight reductions. Birth weight has decreased in recent years, and reductions were greater in infants born to African-American women. These trends might be explained by accumulation of risk factors such as hypertension and prepregnancy obesity that disproportionately affect African-American women. Our results raise the possibility of worsening race disparities in fetal growth.

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.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 at37+0 weeks' gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction.We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported.The "Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be" cohort study methods and procedures can help investigators when they plan future projects.

ObjectiveThe 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 designNuMoM2b 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. A standardized level 3 home sleep test was performed between 6(0)-15(0) weeks' gestation (visit 1) and again between 22(0)-31(0) weeks' gestation (visit 3). Scoring of tests was conducted by a central Sleep Reading Center. Participants and their health care providers were notified if test results met "urgent referral" criteria that were based on threshold levels of apnea hypopnea indices, oxygen saturation levels, or electrocardiogram abnormalities but were not notified of test results otherwise. The primary pregnancy outcomes to be analyzed in relation to maternal sleep disordered breathing arepreeclampsia, gestational hypertension, gestational diabetes mellitus, fetal growth restriction, and preterm birth.ResultsObjective data were obtained at visit 1 on 3261 women, which was 88.1% of the studies that were attempted and at visit 3 on2511 women, which was 87.6% of the studies that were attempted. Basic characteristics of the substudy cohort are reported inthis methods article.ConclusionThe substudy was designed to address important questions regarding the relationship of sleep-disordered breathing onthe risk of preeclampsia and other outcomes of relevance to maternal and child health.

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. Women were excluded for antepartum stillbirth and highly morbid conditions for which route of delivery would not likely impact morbidity including nonreassuring fetal status, cord prolapse, placenta previa, placenta accreta, placental abruption, and severe and unstable maternal conditions (cardiopulmonary collapse, acute respiratory distress syndrome, seizures). Serious maternal complications were defined as: hemorrhage (blood loss ≥1500 mL, blood transfusion, or hysterectomy for hemorrhage), infection (endometritis, wound dehiscence, or wound infection requiring antibiotics, reopening, or unexpected procedure), intensive care unit admission, or death. Delivery route was categorized as classic cesarean delivery (CCD), low transverse cesarean delivery (LTCD), low vertical cesarean delivery (LVCD), and vaginal delivery. Association of delivery route with complications was estimated using multivariable regression models yielding adjusted relative risks (aRR) controlling for maternal age, race, body mass index, hypertension, diabetes, preterm premature rupture of membranes, preterm labor, GA, and hospital of delivery. Results Of 2659 women who met criteria for inclusion in this analysis, 8.6% of women experienced serious maternal complications. Complications were associated with GA and were highest between 23-27 weeks of gestation. The frequency of complications was associated with delivery route; compared with 3.5% of vaginal delivery, 23.0% of CCD (aRR, 3.54; 95% confidence interval (CI), 2.29–5.48), 12.1% of LTCD (aRR, 2.59; 95% CI, 1.77–3.77), and 10.3% of LVCD (aRR, 2.27; 95% CI, 0.68–7.55) experienced complications. There was no significant difference in complication rates between CCD and LTCD (aRR, 1.37; 95% CI, 0.95–1.97) or between CCD and LVCD (aRR, 1.56; 95% CI, 0.48–5.07). Conclusion The risk of maternal complications after early preterm delivery is substantial, particularly in women who undergo cesarean delivery. Obstetricians need to be prepared to manage potential hemorrhage, infection, and intensive care unit admission for early preterm births requiring cesarean delivery.

Over the last century, the incidence of placenta accreta, increta, and percreta, collectively referred to as morbidly adherent placenta, has risen dramatically. Planned cesarean hysterectomy at the time of cesarean delivery is the standard recommended treatment in the United States. Recently, interest in conservative management has resurged, especially in Europe. The aims of this review are the following: (1) to provide an overview of methods used for conservative management, (2) to discuss clinical implications for both clinicians and patients, and (3) to identify areas in need of further research.

Background/Aims: Telomere biology plays a fundamental role in genomic integrity and cell physiology. The newborn setting of telomere length (TL) likely has important implications for telomere dynamics over the lifespan; however, its determinants are poorly understood. Folate is essential for DNA integrity. The maternal compartment is the only source of folate for the developing fetus. We, therefore, tested the hypothesis that variation in maternal folate during pregnancy is associated with newborn TL. Methods: A prospective, longitudinal study was conducted in 119 mother-newborn dyads. Eligible mothers were enrolled at 9.5 (SD ±2.1) weeks gestation and followed through birth. Concentrations of maternal serum folate were measured in the first trimester of pregnancy. Newborn telomere length was measured in cord blood mononuclear cells (CBMC). Results: After accounting for the effects of other established determinants of newborn TL, each 10 ng/ml increase in maternal total folate was associated with a 5.8% increase in median TL (p = 0.03). The median TL in newborns of mother in the lowest quartile of total folate levels was approximately 10% shorter than that of newborns of mothers in the highest folate quartile. Conclusions: Our findings suggest that fetal TL exhibits developmental plasticity, and provide evidence that maternal nutrition may exert a ‘programming' effect on this system.

Preterm premature rupture of the membranes (PPROM) is responsible for one-third of all preterm births and affects 120,000 pregnancies in the United States each year. Effective treatment relies on accurate diagnosis and is gestational age dependent. The diagnosis of PPROM is made by a combination of clinical suspicion, patient history and some simple tests. PPROM is associated with significant maternal and neonatal morbidity and mortality from infection, umbilical cord compression, placental abruption and preterm birth. Subclinical intrauterine infection has been implicated as a major aetiological factor in the pathogenesis and subsequent maternal and neonatal morbidity associated with PPROM. The frequency of positive cultures obtained by transabdominal amniocentesis at the time of presentation with PPROM in the absence of labour is 25-40%. The majority of amniotic fluid infection in the setting of PPROM does not produce the signs and symptoms traditionally used as diagnostic criteria for clinical chorioamnionitis. Any evidence of infection by amniocentesis should be considered carefully as an indication for delivery. Documentation of amniotic fluid infection in women who present with PPROM enables us to triage our therapeutic decision making rationally. In PPROM, the optimal interval for delivery occurs when the risks of immaturity are outweighed by the risks of pregnancy prolongation (infection, abruption and cord accident). Lung maturity assessment may be a useful guide when planning delivery in the 32- to 34-week interval. A gestational age approach to therapy is important and should be adjusted for each hospital's neonatal intensive care unit. Antenatal antibiotics and corticosteroid therapies have clear benefits and should be offered to all women without contraindications. During conservative management, women should be monitored closely for placental abruption, infection, labour and a non-reassuring fetal status. Women with PPROM after 32 weeks of gestation should be considered for delivery, and after 34 weeks the benefits of delivery clearly outweigh the risks.

Objective The purpose of this study was to determine the association of vaginal pH ≥5.0 and vaginal neutrophils >5 per oil field with preterm rupture of membranes (PPROM). Study design This was a secondary analysis of the Vaginal Infections and Prematurity cohort, and was comprised of 12,734 evaluable women enrolled between 23 and 26 weeks' gestation. Women were tested for sexually transmitted infections and vaginal pH. Gram-stained smears were used for the detection of neutrophils. Results In this analysis, 5751 (41.3%) women had neutrophils >5 per oil field, and 2500 (18.0%) had pH ≥5.0. Both elevated pH and neutrophils were present in 1149 women (8.3%). The concomitant presence of both neutrophils and elevated pH was significantly associated with PPROM at 24 to 32 weeks. Conclusion Elevated vaginal pH and neutrophils are most strongly associated with early third-trimester PPROM, reflecting the importance of infection and/or inflammation in the pathogenesis of this condition.

OBJECTIVE: To evaluate the effect of implementation of a human immunodeficiency virus (HIV) educational intervention on universal screening for HIV in a prenatal clinic setting. METHODS: In this retrospective cohort study, frequencies of offering and acceptance of HIV testing were compared before and after an educational intervention performed by an HIV-focused nurse. The records of 293 women seeking prenatal care before the intervention and 206 women seeking prenatal care after the intervention were reviewed for offering and acceptance of HIV testing. Fisher's exact test and logistic regression were used to evaluate the relationship between the educational intervention and the offering and acceptance of HIV testing. RESULTS: The frequency of HIV test offering at first visit and test acceptance before the educational intervention were 96.5% and 74.8%, respectively, and after the intervention were 99.5% and 84.3%, respectively. This improvement in offering (3% change) and acceptance (9.5% change) was statistically significant (offering at first visit: OR = 7.27, 95% CI = 1.02 to 316.9; test acceptance: OR = 1.82, 95% CI = 1.14 to 2.88). Test acceptance was statistically significantly improved in the post-intervention group after controlling for confounding variables (OR = 2.02, 95% CI = 1.2 to 3.39). CONCLUSION: The addition of an HIV-focused nurse to a clinic setting improved the frequency of test offering at first visit and of acceptance of HIV testing by pregnant women.

Objective The purpose of this study was to determine the association of vaginal pH≥5.0 and vaginal neutrophils >5 per oil-field with early preterm birth. Study design This is a secondary analysis of the vaginal infections and prematurity cohort comprised of 13,917 women at 23 and 26 weeks of gestation. All women were tested for sexually transmitted infections and vaginal pH. Gram-stained smears were used for the detection of neutrophils. Results There were 5751 women (41.3%) with neutrophils >5 per oil-field and 2500 women (18.0%) with pH≥5.0. Both elevated pH and neutrophils were present in 1149 women (8.3%). Neutrophils and pH were each significantly associated with spontaneous preterm birth, and the point estimate of the strength of that association increased as the gestational age at delivery decreased. Conclusion Elevated vaginal pH and neutrophils are associated most strongly with the earliest preterm births.

Objective A single-base polymorphism within the promoter of the gene for tumor necrosis factor α at position -308 relative to the transcriptional start site of the gene is correlated with differences in production of tumor necrosis factor α. There are two allelic forms: TNFA1 and TNFA2. The TNFA2 allele is associated with increased production of tumor necrosis factor α. The purpose of this study is to assess the relationship between carriage of the TNFA2 allele and clinical chorioamnionitis. Methods In this retrospective cohort study, previously banked deoxyribonucleic acid from 149 women who had spontaneous labor from 37 to 42 weeks’ gestation was used. Polymerase chain reaction was used for polymorphism assay. Demographic and clinical information was obtained from the medical record. Clinical chorioamnionitis was defined as at least one temperature elevation above 38C combined with at least two of the following signs: maternal or fetal tachycardia, uterine tenderness greater than expected, foul-smelling vaginal discharge, and white blood cell count more than 18,000. Results Chorioamnionitis was present in 18 women (12.1%). Among women who did not carry TNFA2, the chorioamnionitis rate was 7.4%. Among women who carried TNFA2, the chorioamnionitis rate was 24.4%. The relative risk for chorioamnionitis with carriage of TNFA2 was 3.3 (95% confidence interval 1.3, 7.1). This increased risk was not altered after adjustment for race, type of rupture of membranes, intrauterine pressure catheter use, smoking, and prolonged rupture of membranes. Conclusion Carriage of the TNFA2 allele is associated with a more than three-fold increased risk of clinical chorioamnionitis, even when accounting for important clinical and microbiologic risk factors.

Background Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes. Objective 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 complete a daily sleep log for a period of 7 consecutive days. 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 ( 5 am), and top quartile of minutes of wake time after sleep onset 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 mellitus. We used χ 2 tests 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 gestational diabetes. For associations significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. Results In all, 901 eligible women consented to participate; 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of gestational diabetes (odds ratio, 2.24; 95% confidence interval, 1.11–4.53; and odds ratio, 2.58; 95% confidence interval, 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 gestational diabetes remained significant (adjusted odds ratio, 2.06; 95% confidence interval, 1.01–4.19; and adjusted odds ratio, 2.37; 95% confidence interval, 1.13–4.97, respectively). Additionally, after adjusting separately for age, body mass index, and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with gestational diabetes. No associations were demonstrated between the sleep quality measures (wake after sleep onset, sleep fragmentation) and hypertensive disorders or gestational diabetes. Conclusion Our results demonstrate a relationship between short sleep duration and later sleep midpoint with gestational diabetes. Our data suggest independent contributions of these 2 sleep characteristics to the risk for gestational diabetes in nulliparous women.

Importance Spontaneous preterm birth is a leading cause of infant mortality. Prediction, largely based on prior pregnancy outcomes, is not possible in women pregnant for the first time. Objective To assess the accuracy of universal screening to predict spontaneous preterm birth in nulliparous women using serial measurements of vaginal fetal fibronectin levels and cervical length. Design, Settings, and Participants A prospective observational cohort study of nulliparous women with singleton pregnancies, from 8 clinical sites across the United States between October 2010 and May 2014. Women and clinicians were blinded to results unless cervical shortening less than 15 mm was identified. Exposures Transvaginal cervical length and quantitative vaginal fetal fibronectin levels were reviewed at 2 study visits 4 or more weeks apart. Main Outcomes and Measures Spontaneous preterm birth at less than 37 weeks was the primary outcome. Cervical length and quantitative fetal fibronectin were considered independently and together at each visit. Measurement distributions were compared for spontaneous preterm birth vs all other births. Spontaneous preterm birth before 32 weeks was a secondary outcome. Results The study included 9410 women (median age, 27.0 [interquartile range, 9.0] years; 60.7% non-Hispanic white, 13.8% non-Hispanic black, 16.5% Hispanic, 4.0% Asian, and 5.1% other), of whom 474 (5.0%) had spontaneous preterm births, 335 (3.6%) had medically indicated preterm births, and 8601 (91.4%) had term births. Among women with spontaneous preterm birth, cervical length of 25 mm or less occurred in 35 of 439 (8.0%) at 16 to 22 weeks’ gestation and in 94 of 403 (23.3%) at 22 to 30 weeks’ gestation. Fetal fibronectin levels of 50 ng/mL or greater at 16 to 22 weeks identified 30 of 410 women (7.3%) with spontaneous preterm birth and 31 of 384 (8.1%) at 22 to 30 weeks. The area under the receiver operating characteristic curve for screening between 22 and 30 weeks for fetal fibronectin level alone was 0.59 (95% CI, 0.56-0.62), for transvaginal cervical length alone was 0.67 (95% CI, 0.64-0.70), and for the combination as continuous variables was 0.67 (95% CI, 0.64-0.70). Conclusions and Relevance Among nulliparous women with singleton pregnancies, quantitative vaginal fetal fibronectin and serial transvaginal ultrasound cervical length had low predictive accuracy for spontaneous preterm birth. These findings do not support routine use of these tests in such women.

To test the feasibility of conducting a pragmatic randomized controlled trial (RCT) comparing the International Association of Diabetes in Pregnancy Study Groups (IADPSG) versus Carpenter-Coustan diagnostic criteria for gestational diabetes (GDM), and to examine patient and provider views on GDM screening. A single-blinded pragmatic pilot RCT. Participants with a singleton pregnancy between 24 and 28 weeks gestation received a 50 g oral glucose challenge test and if the value was

Reference charts for classifying and monitoring pregnancy weight gain in severely obese women do not exist. The goal was to construct pregnancy weight-gain-for-gestational-age z-score charts for overweight and obese mothers, stratified by severity of obesity.Serial weight gain measurements were abstracted from 1047, 1202, 1267, and 730 overweight, class I, II, and III obese women, respectively, delivering uncomplicated term pregnancies at Magee-Womens Hospital in Pittsburgh, PA. Multi-level linear regression models were used to express serial weight gain measurements as a function of gestational age.There were a median [interquartile range] of 11 [9-12] and 11 [9-13] serial weight measurements for overweight and obese (class I, II, and III) women, respectively. The rate of weight gain was minimal until 15-20 weeks and then increased in a slow, linear manner until term. The slope of weight gain flattened as pre-pregnancy BMI increased. Charts were created describing the mean, standard deviation, and select percentiles of weight gain in class I, II, and III obese and overweight pregnancies.These charts are an innovative tool for studying the association between gestational weight gain and adverse pregnancy outcomes.

Preeclampsia is a multisystem disorder diagnosed by new-onset hypertension and proteinuria. In developed countries, the perinatal mortality rate among preeclamptic pregnancies is five times as great as non-preeclamptic pregnancies, 1 and indicated preterm deliveries for preeclampsia account for 15% of preterm births.2 Mothers who develop preeclampsia are at elevated risk of abruptio placentae, acute renal failure, and neurologic and cardiovascular complications. 1 Moreover, preeclampsia contributes to 18% of maternal deaths in the U.S. and 20–80% of maternal deaths in developing countries. 1,3 Delivery is the only known cure for preeclampsia, and few interventions have been effective in preventing the disorder. There is a growing interest in the role of maternal vitamin D status in the development of preeclampsia. Vitamin D is a prohormone that is either made in the skin through ultraviolet B radiation exposure or ingested orally. 4 Vitamin D deficiency is widespread in U.S. pregnant women 5–8 due to inadequate sunlight exposure, limited vitamin D-rich food sources, and use of prenatal vitamins with low doses of vitamin D. 4 Vitamin D has diverse and protean functions that may be relevant in the pathophysiology of preeclampsia, including abnormal placental implantation and angiogenesis, excessive inflammation, hypertension, and immune dysfunction. 4,9–12 Unfortunately, most vitamin D-preeclampsia research has been conducted in predominantly Caucasian populations with small numbers of preeclampsia cases, and results have been inconsistent. 13–21 We sought to determine the association between maternal vitamin D status at ≤26 weeks and the risk of preeclampsia in a large, geographically-diverse U.S. multicenter cohort of pregnant women.

To examine the association between second-trimester maternal serum 25-hydroxyvitamin D concentrations and risk of small for gestational age (SGA) in singleton live births.We assayed serum samples at 12-26 weeks of gestation for 25-hydroxyvitamin D in a sample of participants in a multicenter clinical trial of low-dose aspirin for the prevention of preeclampsia in high-risk women (n=792). Multivariable log-binomial regression models were used to assess the association between 25-hydroxyvitamin D and risk of SGA (birth weight less than the 10 percentile for gestational age) after adjustment for confounders including maternal prepregnancy obesity, race, treatment allocation, and risk group.Thirteen percent of neonates were SGA at birth. Mean (standard deviation) 25-hydroxyvitamin D concentrations were lower in women who delivered SGA (57.9 [29.9] nmol/L) compared with non-SGA neonates (64.8 [29.3] nmol/L, P=.028). In adjusted models, 25-hydroxyvitamin D concentrations of 50-74 nmol/L and 75 nmol/L or greater compared with less than 30 nmol/L were associated with 43% (95% confidence interval [CI] 0.33-0.99) and 54% (95% CI 0.24-0.87) reductions in risk of SGA, respectively. Race and maternal obesity each modified this association. White women with 25-hydroxyvitamin D 50 nmol/L or greater compared with less than 50 nmol/L had a 68% reduction in SGA risk (adjusted risk ratio 0.32, 95% CI 0.17-0.63) and nonobese women with 25-hydroxyvitamin D 50 nmol/L or greater compared with less than 50 nmol/L had a 50% reduction in SGA risk (adjusted risk ratio 0.50, 95% CI 0.31-0.82). There was no association between 25-hydroxyvitamin D and risk of SGA in black or obese mothers.Maternal vitamin D status in the second trimester is associated with risk of SGA among all women and in the subgroups of white and nonobese women.II.

Purpose The objective of this case-cohort study was to evaluate the relationship between maternal 25-hydroxyvitamin D (25(OH)D) concentration and preeclampsia overall and by severity. Methods From an eligible cohort of 12,861 women who had serum banked from aneuploidy screening in Pittsburgh, Pennsylvania from 1999 to 2010, we randomly sampled a subcohort of 2327 pregnancies and all remaining preeclampsia cases (n = 650 cases). Preeclampsia (defined as new-onset hypertension and proteinuria) and its mild and severe forms were identified using ICD-9 codes. Maternal serum collected at 20 weeks or less gestation was measured for 25(OH)D. We used log-binomial regression with restricted cubic splines to estimate the association between 25(OH)D and preeclampsia after adjusting for confounders. Results Approximately 21% of the randomly selected sample had 25(OH)D less than 50 nmol per L. We found that the adjusted risk of preeclampsia declined as serum 25(OH)D increased to 50 nmol per L and then plateaued (test of nonlinearity P