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1.
J Matern Fetal Neonatal Med ; : 1-10, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34747312

RESUMO

OBJECTIVE: To examine pregnancy outcomes in women with treated and untreated anxiety in a well-characterized cohort. STUDY DESIGN: Secondary analysis of the NuMoM2b study, a prospective multi-center cohort of nulliparous women. Anxiety was assessed at 6 weeks 0 days - 13 weeks 6 days using the State Trait Anxiety Inventory (STAI-T). Women were divided into three groups: anxiety and medical treatment, anxiety and no medical treatment, and no anxiety (controls). The primary outcome was a composite of preterm birth, small for gestational age infant, placental abruption (clinically diagnosed), and hypertensive disorders of pregnancy. Multivariable logistic regression was used to adjust for potential confounding variables. RESULTS: Among 8293 eligible women, 24% (n = 1983) had anxiety; 311 were treated medically. The composite outcome (preterm birth, small for gestational age infant, placental abruption, hypertensive disorders of pregnancy) occurred more often in women with untreated anxiety than controls (28.6% vs 25.9%, p=.02), with no difference between treated anxiety and controls (27.7% vs 25.9%, p=.49). After adjustment for confounders, including controlling for depression, there were no differences in the primary outcome among groups. Untreated anxiety remained associated with increased odds of neonatal intensive care unit admission. CONCLUSION: Anxiety occurred in almost a quarter of nulliparas. There was no association between treated or untreated anxiety and our primary outcome of adverse pregnancy outcomes after adjustment for confounders. However, neonates born to women with untreated anxiety were at increased risk for NICU admission.

2.
Menopause ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34636354

RESUMO

OBJECTIVE: Longer menstrual cycles have been associated with greater risk of cardiovascular disease, supporting a contribution of abnormal ovarian function. We aimed to characterize trajectories of menstrual cycle length over the menopause transition (MT) and test whether these trajectories are associated with postmenopausal markers of subclinical atherosclerosis. METHODS: Women from the Study of Women's Health Across the Nation Daily Hormone Study were included if they had an observed date of the final menstrual period (FMP), recorded cycle lengths from ≥2 annual menstrual cycles (mean±SD: 4.22 ± 1.91 cycles), and had measurements of postmenopausal carotid intima-media thickness (cIMT) and/or brachial-ankle pulse wave velocity (baPWV). Trajectories of cycle length over the MT were identified using group-based trajectory modeling and linked with cIMT and baPWV using linear regression. RESULTS: We studied 428 women who had 1,808 cycles over the MT (45.1 ± 2.3 y old at baseline visit), and of whom 263 had cIMT, and 213 had baPWV measured postmenopausally (after 13.88 ±â€Š0.42 and 15.25 ±â€Š0.70 y since baseline visit, respectively). Three distinct trajectories of cycle length were identified: stable (no changes in cycle length over the MT among 62.1% of women), late increase (a late increase 2 y before the FMP among 21.8%), and early-increase (an early increase 5 y before the FMP among 16.2%). Women with the late-increase pattern had significantly lower postmenopausal cIMT (0.72 mm) and baPWV (1392 cm/s) levels than the stable group (0.77 mm and 1508 cm/s, respectively) adjusting for race, concurrent age, socioeconomic status, physical activity level, and premenopausal cardiovascular risk profile. CONCLUSIONS: Patterns of cycle length over the MT seem to be a marker of future vascular health that may help identify groups at greater or lesser risk of atherosclerosis after menopause.

3.
J Matern Fetal Neonatal Med ; : 1-8, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470115

RESUMO

OBJECTIVE: Marijuana (MJ) use is associated with adverse effects on fetal growth. We aimed to investigate the timing of suboptimal fetal growth onset in MJ-exposed pregnancies. In addition, we aimed to explore the relationship between MJ-exposure and both abnormal uterine artery (UtA) Doppler parameters and small for gestational age (SGA). STUDY DESIGN: This was a secondary analysis of a prospective multicenter cohort that enrolled nulliparous individuals delivering non-anomalous fetuses beyond 20 weeks' gestation. Marijuana exposure was ascertained by self-report or clinical urine toxicology testing. Ultrasound estimated fetal weights (EFWs) were assessed in participants at both 16w0d-21w6d and 22w0d-29w6d. EFWs and birth weight (BW) were converted to weight percentiles (wPCT). EFW and BW wPCTs were calculated using population-based standards. Additionally, a customized standard designed to be applicable to both EFWs and BWs within the same model was also used to allow for EFW to BW percentile trajectories. The primary outcome, longitudinal wPCT, was compared between individuals with and without MJ use in a linear mixed-effects regression model adjusting for tobacco. For modeling, wPCT was smoothed across gestational age; MJ was estimated as an intercept and linear difference in the slope of gestational age. UtA Doppler notching, resistance index (RI), and pulsatility index (PI) at 16w0d-21w6d were compared using t-test and χ2. SGA at delivery was also compared. RESULTS: Nine thousand one hundred and sixty-three individuals met inclusion criteria; 136 (1.5%) used MJ during pregnancy. Individuals who used MJ were more likely to be younger, identify as non-Hispanic Black, and have had less education. Fetuses exposed to MJ had lower wPCT beginning at 28 weeks using population-based and customized standards, when compared to those without exposure. UtA notching, PI, and RI were similar between groups. SGA was more frequent in neonates exposed to MJ using both population-based (22 vs. 9%, p<.001) and customized (25 vs. 14%, p<.001) curves. CONCLUSIONS: MJ-exposed fetuses were estimated to be smaller than unexposed fetuses starting at 28 weeks' gestation across both growth standards without a difference in UtA Doppler parameters.

4.
J Matern Fetal Neonatal Med ; : 1-10, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582307

RESUMO

BACKGROUND: While neonates with birth weight <10th percentile are at increased risk of morbidity and mortality, most of these are constitutionally small and not at increased risk. There are no current strategies that reliably distinguish constitutionally small neonates from small neonates at the highest risk of morbidity, so additional tools for risk stratification are needed. OBJECTIVE: Our objectives were to identify factors that are independently associated with perinatal morbidity among neonates with birth weight <10th percentile (small for gestational age, SGA) and to create predictive models of perinatal morbidity among SGA neonates based on the timing of information availability. STUDY DESIGN: This secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, was a nested case-control study. Participants were prospectively enrolled at eight U.S. centers, with data collection occurring at three standard time points during pregnancy and again after delivery. Our analysis included neonates with birth weights <10th percentile and excluded those with major congenital malformations or suspected or confirmed aneuploidy. The primary outcome was a composite of perinatal morbidity, defined as NICU admission >48 h, NEC, sepsis, RDS, mechanical ventilation, retinopathy of prematurity, seizures, grade 3 or 4 IVH, stillbirth, or death before discharge. Cases were SGA neonates that experienced the primary outcome, and controls were SGA neonates that did not. Maternal factors for potential inclusion in predictive modeling were drawn from a broad list of variables collected as part of the NuMoM2B study, including demographic, anthropometric, clinical, ultrasound, social/behavioral, dietary, and psychological variables. Characteristics that were different in bivariate analysis between cases and controls then underwent further evaluation and refinement. Continuous and multi-category variables were assessed using multiple approaches, including as continuous variables, using standard categories (such as for BMI) as well as empirically-derived cut-points identified by receiver-operating characteristics methodology. The approach for each variable that resulted in the best performance was selected for use in modeling. After variable optimization, multivariable analysis was used to derive prediction models using factors known at mid-pregnancy (Model 1) and delivery (Model 2). RESULTS: Of the original cohort, 865 were eligible and analyzed, with 134 (15.5%) experiencing the primary outcome. After bivariable and multivariable analysis, these variables were included in Model 1: BMI, stress level, diastolic blood pressure, narcotic use (all in 1st trimester), and uterine artery pulsatility index at 16-21 weeks. Model 2 added the following variables to Model 1: preterm delivery, preeclampsia, and suspected fetal growth restriction. When models 1 and 2 were empirically tested and compared to predicted performance to demonstrate calibration, observed morbidity rates approximately followed expected rates within deciles. Models 1 and 2 had respective areas under the receiver-operating characteristic curve of 0.72 (95% CI 0.67-0.76) and 0.84 (0.80-0.88), to predict the composite morbidity. CONCLUSION: Using a deeply phenotyped cohort of nulliparous women, we created two models with the moderate-good prediction of perinatal morbidity among SGA neonates. TRIAL REGISTRATION: clinicaltrials.gov ID: NCT01322529.

5.
Am J Obstet Gynecol ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34331895

RESUMO

BACKGROUND: As early life interventions for congenital heart disease improve, more patients are living to adulthood and are considering pregnancy. Scoring and classification systems predict the maternal cardiovascular risk of pregnancy in the context of congenital heart disease, but these scoring systems do not assess the potential subsequent risks following pregnancy. Data on the long-term cardiac outcomes after pregnancy are unknown for most lesion types. This limits the ability of healthcare practitioners to thoroughly counsel patients who are considering pregnancy in the setting of congenital heart disease. OBJECTIVE: We aimed to evaluate the association between pregnancy and the subsequent long-term cardiovascular health of individuals with congenital heart disease. STUDY DESIGN: This was a retrospective longitudinal cohort study of individuals identifying as female who were receiving care in two adult congenital heart disease centers from 2014 to 2019. Patient data were abstracted longitudinally from a patient age of 15 years (or from the time of entry into the healthcare system) to the conclusion of the study, death, or exit from the healthcare system. The primary endpoint, a composite adverse cardiac outcome (death, stroke, heart failure, unanticipated cardiac surgery, or a requirement for a catheterized procedure), was compared between parous (at least one pregnancy >20 weeks' gestation) and nulliparous individuals. By accounting for differences in the follow-up, the effect of pregnancy was estimated based on the time to the composite adverse outcome in a proportional hazards regression model adjusted for the World Health Organization class, baseline cardiac medications, and number of previous sternotomies. Participants were also categorized according to their lesion type, including septal defects (ventricular septal defects, atrial septal defects, atrioventricular septal defects, or atrioventricular canal defects), right-sided valvular lesions, left-sided valvular lesions, complex cardiac anomalies, and aortopathies, to evaluate if there is a differential effect of pregnancy on the primary outcome when adjusting for lesion type in a sensitivity analysis. RESULTS: Overall, 711 individuals were eligible for inclusion; 209 were parous and 502 nulliparous. People were classified according to the World Health Organization classification system with 86 (12.3%) being classified as class I, 76 (10.9%) being classified as class II, 272 (38.9%) being classified as class II to III, 155 (22.1%) being classified as class III, and 26 (3.7%) being classified as class IV. Aortic stenosis, bicuspid aortic valve, dilated ascending aorta or aortic root, aortic regurgitation, and pulmonary insufficiency were more common in parous individuals, whereas dextro-transposition of the great arteries, Turner syndrome, hypoplastic right heart, left superior vena cava, and other cardiac diagnoses were more common in nulliparous individuals. In multivariable modeling, pregnancy was associated with the composite adverse cardiac outcome (36.4%% vs 26.1%%; hazard ratio, 1.83; 95% confidence interval, 1.25-2.66). Parous individuals were more likely to have unanticipated cardiac surgery (28.2% vs 18.1%; P=.003). No other individual components of the primary outcome were statistically different between parous and nulliparous individuals in cross-sectional comparisons. The association between pregnancy and the primary outcome was similar in a sensitivity analysis that adjusted for cardiac lesion type (hazard ratio, 1.61; 95% confidence interval, 1.10-2.36). CONCLUSION: Among individuals with congenital heart disease, pregnancy was associated with an increase in subsequent long-term adverse cardiac outcomes. These data may inform counseling of individuals with congenital heart disease who are considering pregnancy.

6.
Am J Obstet Gynecol MFM ; 3(6): 100450, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34325015

RESUMO

BACKGROUND: Randomized controlled trials are considered the highest level of evidence but fewer than half are reproducible. A rigorous methodology improves trial quality, but reproducibility may be limited by a lack of transparency in reporting. The Consolidated Standards of Reporting Trials guidelines define reporting standards, and pretrial registration requires a predefined methodology and predefined outcomes. OBJECTIVE: We evaluated obstetrics and gynecology trials published in 6 journals in terms of their adherence to the Consolidated Standards of Reporting Trials guidelines. Second, we evaluated pretrial registration compliance and concordance between the registry and publication. Furthermore, we evaluated the differences in trial characteristics among randomized controlled trials with the highest level of compliance and those with lower levels of compliance and adherence to guidelines by journal type. STUDY DESIGN: This was a cross-sectional study of obstetrics and gynecology trials published between 2017 and 2019 in 6 journals (American Journal of Obstetrics & Gynecology, BJOG: An International Journal of Obstetrics and Gynaecology, Obstetrics & Gynecology, The Journal of the American Medical Association, The Lancet, and The New England Journal of Medicine). Randomized controlled trials were identified via PubMed and manual journal archive searches. The primary outcome was adequate compliance with the Consolidated Standards of Reporting Trials guidelines defined as ≥80% of the checklist items present. Secondary outcomes included completion of pretrial registration and concordance between the pretrial registration and publication in terms of the outcomes and sample size. We compared the characteristics between trials with adequate compliance and those with inadequate compliance. Secondary analyses included comparisons of characteristics of the trials in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines with those of the trials in lower quartiles and compliance with guidelines in obstetrics-gynecology vs non-obstetrics-gynecology journals. In an exploratory analysis, trends in compliance with the Consolidated Standards of Reporting Trials guidelines across the study period were assessed. A post hoc sensitivity analysis evaluated the outcomes after the exclusion of 2 retracted trials. RESULTS: Of the 170 trials included, 80% (95% confidence interval, 74%-86%) were adequately compliant with the Consolidated Standards of Reporting Trials manuscript guidelines and 66% (95% confidence interval, 59%-73%) were compliant with the abstract guidelines. Nearly all trials (98%) reported pretrial registration. Concordance between pretrial registration and publication in terms of the primary outcomes was identified for 77% of the trials, concordance in terms of the secondary outcomes was observed in 32% of the trials, and concordance in terms of sample size was observed in 60% of the trials. Trials with adequate compliance were more likely to be preregistered, include an a priori power calculation, and use an intent to treat analysis. Trials in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines were more likely to be multicenter, international, and government funded. More trials from non-obstetrics-gynecology journals were in the top quartile for compliance with the Consolidated Standards of Reporting Trials guidelines than trials from obstetrics-gynecology journals (64.9% vs 25.7%; P<.001). No significant trends in adequate compliance were identified across the study period. Results did not differ significantly in the sensitivity analysis. CONCLUSION: Of all the trials included, 20% of obstetrics-gynecology trials published in 6 high-impact journals were not compliant with the Consolidated Standards of Reporting Trials guidelines, and there were major discrepancies between pretrial registration and publication. Transparency, reproducibility, and scientific rigor in obstetrics and gynecology trial reporting needs to be improved.


Assuntos
Ginecologia , Obstetrícia , Estudos Transversais , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes
7.
Addiction ; 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34142398

RESUMO

BACKGROUND AND AIMS: To estimate during pregnancy correlations between frequency of self-reported use of marijuana and quantified marijuana metabolite in biospecimens including urine, sera and umbilical cord homogenate. DESIGN: Prospective cohort. SETTING: Two urban hospitals in Colorado with legal recreational and medicinal marijuana. PARTICIPANTS: Pregnant women (<16 weeks gestation) self-reporting marijuana use. MEASUREMENTS: Participants completed a written self-report survey and provided biospecimens at <16 weeks gestation (n = 46), 18 to 22 weeks gestation (n = 43), 32 to 36 weeks gestation (n = 39), and delivery (n = 37). Self-reported marijuana use frequency was calculated based on past-month days of use multiplied by number of daily uses. Maternal urine and sera were tested for presence (>5 ng/mL) of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH). Liquid chromatography tandem mass spectrometry quantified THC-COOH in umbilical cord homogenate (ng/g). Last marijuana use by any measure was recorded to evaluate the time frame over which THC-COOH remains detectable (>0.10 ng/g) in cord. FINDINGS: From December 2017 through May 2019, 51 pregnant women enrolled, and 46 were included in analyses (2 withdrew and 3 had a spontaneous abortion). The majority were normal weight, White or Black race, and insured by Medicaid. At the time of enrollment between 7 to 15 weeks' gestation, 87% had ongoing use by self-report, or positive urine or serum. The majority (33 [66%]) stopped using before delivery. Sera and urine results were strongly correlated with self-reported use frequency (Spearman correlation coefficient [r] range 0.70-0.87 across visits, P < 0.001), and with each other. There was only one positive cord result when use stopped before 22 weeks. Frequency of self-reported marijuana use at delivery had strong correlation with quantified cord THC-COOH (r = 0.80, 95% CI = 0.62-0.89). CONCLUSIONS: Quantified umbilical cord THC-COOH appears to strongly correlate with frequency of maternal marijuana use in the last month of pregnancy. Earlier use can be measured by either quantitative urine or serum assay.

8.
Am J Perinatol ; 38(12): 1223-1230, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34169500

RESUMO

OBJECTIVE: Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower p-value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a p-value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance. STUDY DESIGN: A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and p-values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a p-value significance threshold of 0.005 versus be reinterpreted as "suggestive" (defined as p-value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics. RESULTS: Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with p <0.05 at the time of publication, 54.4% (n = 49) would maintain significant (p < 0.005), while 45.6% (n = 41) would become suggestive using the lower threshold. Most RCTs utilized a single (90.1%) versus composite (8.9%) primary outcome type, used an intent-to-treat analysis (73.3%), and studied a drug intervention (46.5%). Methodologically, 23.7% did not prespecify analysis type, 28.2% did not meet the pre-determined sample size, and 9.4% did not report an a priori sample size calculation. Studies maintaining significance were more likely to be international and report a funding source. CONCLUSION: Adopting a p-value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified. KEY POINTS: · New p-value threshold results in reinterpretation of nearly half of RCT results in OB/Gyn literature.. · Highly variable methodological quality was identified.. · Reduced use of binary interpretations of significance is necessary..

9.
Am J Perinatol ; 38(10): 993-998, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33934327

RESUMO

OBJECTIVE: Respiratory distress syndrome (RDS) is implicated in 30% of neonatal deaths. Since prostaglandins promote surfactant secretion and labor is associated with a lower risk of RDS in term neonates, it is plausible that synthetic prostaglandin (sPG) exposure is associated with a lower risk of RDS. Thus, we evaluated the association between sPG exposure and RDS in neonates born after the induction of labor (IOL). STUDY DESIGN: Secondary analysis of women with singleton pregnancies undergoing IOL at 340/7 to 420/7 weeks in the nuMoM2b study, a multicenter prospective cohort of nulliparous women. RDS rates and secondary neonatal outcomes in neonates with intrapartum sPG exposure were compared with those who had IOL with non-sPG methods (e.g., balloon catheter, amniotomy, oxytocin, and laminaria). Logistic regression models estimated the association of sPG with RDS and with secondary outcomes after adjustment for clinical and demographic factors (including gestational age). A sensitivity analysis was performed in which analysis was restricted to those with an admission cervical dilation ≤2 cm. RESULTS: Of 10,038 women in the total cohort, 3,071 met inclusion criteria; 1,444 were exposed and 1,627 were unexposed to sPGs. Antenatal corticosteroid exposure rates were low (3.0%) and similar between groups. In univariable analysis, neonates with sPG exposure had higher rates of RDS (3.2 vs. 2.0%, odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.01-2.50). This relationship was similar by gestational age at delivery (term vs. preterm, interaction p = 0.14). After adjustment, the association between sPG and RDS was no longer significant (adjusted odds ratio: 1.4, 95% CI: 0.9-2.3). When analysis was restricted to subjects with admission cervical dilation of ≤2 cm, there was also no association between sPG exposure and RDS. CONCLUSION: In pregnancies between 34 and 42 weeks of gestation, exposure to sPG for cervical ripening or labor induction was not associated with newborn RDS. KEY POINTS: · RDS is implicated in 30% of neonatal deaths.. · sPG exposure was not associated with RDS.. · Avoiding preterm birth remains crucial in RDS prevention..

10.
Am J Perinatol ; 38(7): 676-682, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31756754

RESUMO

OBJECTIVE: Our objective was to test the association of fetal adrenal size with perinatal morbidity among fetuses with fetal growth restriction (FGR; estimated fetal weight [EFW] < 10th percentile). STUDY DESIGN: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) adrenal study, which measured fetal adrenal gland size at 22 to 30 weeks' gestation. We analyzed the transverse adrenal area (TAA) and fetal zone area (absolute measurements and corrected for fetal size) and the ratio of the fetal zone area to the total transverse area using a composite perinatal outcome of stillbirth, neonatal intensive care unit admission, respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, sepsis, mechanical ventilation, seizure, or death. Among fetuses with FGR, adrenal measurements were compared between those that did and did not experience the composite perinatal outcome. RESULTS: There were 1,709 eligible neonates. Seven percent (n = 120) were diagnosed with FGR at the time of adrenal measurement, and 14.7% (n = 251) experienced perinatal morbidity. EFW-corrected and absolute adrenal measurements were similar among fetuses with and without FGR as well as among those who did and did not experience morbidity. The area under the curve for corrected TAA was 0.52 (95% confidence interval 0.38-0.67). CONCLUSION: In our cohort, adrenal size was not associated with risk of morbidity among fetuses with FGR.

11.
Am J Perinatol ; 2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33368093

RESUMO

OBJECTIVE: The study aimed to assess the feasibility of creating and transplanting human umbilical cord mesenchymal stem cell sheets applied to a rat model of hysterotomy, and additionally to determine benefits of human umbilical cord mesenchymal stem cell sheet transplantation in reducing uterine fibrosis and scarring. STUDY DESIGN: Human umbilical cord mesenchymal stem cell sheets are generated by culturing human umbilical cord mesenchymal stem cells on thermo-responsive cell culture plates. The temperature-sensitive property of these culture dishes facilitates normal cell culture in a thin contiguous layer and allows for reliable recovery of intact stem cell sheets without use of destructive proteolytic enzymes.We developed a rat hysterotomy model using nude rats. The rat uterus has two distinct horns: one horn provided a control/untreated scarring site, while the second horn was the cell sheet transplantation site.On day 14 following surgery, complete uteri were harvested and subjected to histologic evaluations of all hysterotomy sites. RESULTS: The stem cell sheet culture process yielded human umbilical cord mesenchymal stem cell sheets with surface area of approximately 1 cm2.Mean myometrial thickness in the cell sheet-transplanted group was 274 µm compared with 191 µm in the control group (p = 0.02). Mean fibrotic surface area in the human umbilical cord mesenchymal stem cell sheet-transplanted group was 95,861 µm2 compared with 129,185 µm2 in the control group. Compared with control horn sites, cell sheet-transplanted horns exhibited significantly smaller fibrotic-to-normal myometrium ratios (0.18 vs. 0.27, respectively, p = 0.029). Mean number of fibroblasts in cell sheet-transplanted horns was significantly smaller than the control horns (483 vs. 716/mm2, respectively, p = 0.001). CONCLUSION: Human umbilical cord mesenchymal stem cell sheet transplantation is feasible in a rat model of hysterotomy. Furthermore, use of stem cell sheets reduces fibroblast infiltration and uterine scar fibrotic tissue formation during hysterotomy healing, potentially mitigating risks of uterine scar formation. KEY POINTS: · Stem cell sheet transplanted to hysterotomy promotes myometrial regeneration and reduced fibrotic tissue formation.. · This study demonstrates the feasibility of using human umbilical cord mesenchymal stem cell sheets..

12.
Obstet Gynecol ; 136(6): 1095-1102, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33156199

RESUMO

OBJECTIVE: To characterize stillbirths associated with pregestational diabetes and gestational diabetes mellitus (GDM) in a large, prospective, U.S. case-control study. METHODS: A secondary analysis of stillbirths among patients enrolled in a prospective; multisite; geographically, racially, and ethnically diverse case-control study in the United States was performed. Singleton gestations with complete information regarding diabetes status and with a complete postmortem evaluation were included. A standard evaluation protocol for stillbirth cases included postmortem evaluation, placental pathology, clinical testing as performed at the discretion of the health care professional, and a recommended panel of tests. A potential cause of death was assigned to stillbirth cases using a standardized classification tool. Demographic and delivery characteristics among women with pregestational diabetes and GDM were compared with characteristics of women with no diabetes in pairwise comparisons using χ or two-sample t tests as appropriate. Sensitivity analysis was performed excluding pregnancies with genetic conditions or major fetal malformations. RESULTS: Of 455 stillbirth cases included in the primary analysis, women with stillbirth and diabetes were more likely to be older than 35 years and have a higher body mass index. They were also more likely to have a gestational hypertensive disorder than women without diabetes (28% vs 9.1%; P<.001). Women with pregestational diabetes had more large-for-gestational-age (LGA) neonates (26% vs 3.4%; P<.001). Stillbirths occurred more often at term in women with pregestational diabetes (36%) and those with GDM (52%). Maternal medical complications, including pregestational diabetes and others, were more often identified as a probable or possible cause of death among stillbirths with maternal diabetes (43% vs 4%, P<.001) as compared with stillbirths without diabetes. CONCLUSION: Compared with stillbirths in women with no diabetes, stillbirths among women with pregestational diabetes and GDM occur later in pregnancy and are associated with hypertensive disorders of pregnancy, maternal medical complications, and LGA.


Assuntos
Diabetes Gestacional/epidemiologia , Hipertensão Induzida pela Gravidez/epidemiologia , Complicações na Gravidez/epidemiologia , Gravidez em Diabéticas/epidemiologia , Natimorto/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Diabetes Gestacional/etnologia , Feminino , Humanos , Hipertensão Induzida pela Gravidez/etnologia , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/etnologia , Gravidez em Diabéticas/etnologia , Cuidado Pré-Natal , Estudos Prospectivos , Natimorto/etnologia , Estados Unidos/epidemiologia , Adulto Jovem
13.
Am J Perinatol ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32971561

RESUMO

OBJECTIVE: Marijuana use is associated with placenta-mediated adverse pregnancy outcomes including fetal growth restriction, but the mechanism remains uncertain. The objective was to evaluate the association between maternal marijuana use and the feto-placental weight ratio (FPR). Secondarily, we aimed to compare placental histology of women who used marijuana to those who did not. STUDY DESIGN: This was a secondary analysis of singleton pregnancies enrolled in a multicenter and case-control stillbirth study. Prior marijuana use was detected by electronic medical record abstraction or cord homogenate positive for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Prior tobacco use was detected by self-report or presence of maternal serum cotinine. Stillbirths and live births were considered separately. The primary outcome was FPR. Association of marijuana use with FPR was estimated with multivariable linear modeling adjusted for fetal sex, preterm birth, and tobacco use. Comparisons between groups for placental histology were made using Chi-square and stratified by live birth and stillbirth, term and preterm deliveries, and fetal sex. RESULTS: Of 1,027 participants, 224 were stillbirths and 803 were live births. Overall, 41 (4%) women used marijuana during the pregnancy. The FPR ratio was lower among exposed offspring but reached statistical significance only for term stillbirths (mean 6.84 with marijuana use vs. mean 7.8 without use, p < 0.001). In multivariable modeling, marijuana use was not significantly associated with FPR (p = 0.09). There were no differences in histologic placental features among those with and without marijuana use overall or in stratified analyses. CONCLUSION: Exposure to marijuana may not be associated with FPR. Similarly, there were no placental histologic features associated with marijuana exposure. Further study of the influence of maternal marijuana use on placental development and function is warranted to better understand the association between prenatal marijuana use and poor fetal growth. KEY POINTS: · Maternal marijuana exposure was not associated with the feto-placental weight ratio.. · Marijuana exposure was not associated with differences in placental histology.. · Concerning trend toward lower feto-placental weight ratios among marijuana-exposed stillbirths..

15.
Obstet Gynecol ; 135(3): 644-652, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028503

RESUMO

OBJECTIVE: Umbilical cord abnormalities are commonly cited as a cause of stillbirth, but details regarding these stillbirths are rare. Our objective was to characterize stillbirths associated with umbilical cord abnormalities using rigorous criteria and to examine associated risk factors. METHODS: The Stillbirth Collaborative Research Network conducted a case-control study of stillbirth and live births from 2006 to 2008. We analyzed stillbirths that underwent complete fetal and placental evaluations and cause of death analysis using the INCODE (Initial Causes of Fetal Death) classification system. Umbilical cord abnormality was defined as cord entrapment (defined as nuchal, body, shoulder cord accompanied by evidence of cord occlusion on pathologic examination); knots, torsions, or strictures with thrombi, or other obstruction by pathologic examination; cord prolapse; vasa previa; and compromised fetal microcirculation, which is defined as a histopathologic finding that represents objective evidence of vascular obstruction and can be used to indirectly confirm umbilical cord abnormalities when suspected as a cause for stillbirth. We compared demographic and clinical factors between women with stillbirths associated with umbilical cord abnormalities and those associated with other causes, as well as with live births. Secondarily, we analyzed the subset of pregnancies with a low umbilical cord index. RESULTS: Of 496 stillbirths with complete cause of death analysis by INCODE, 94 (19%, 95% CI 16-23%) were associated with umbilical cord abnormality. Forty-five (48%) had compromised fetal microcirculation, 27 (29%) had cord entrapment, 26 (27%) knots, torsions, or stricture, and five (5%) had cord prolapse. No cases of vasa previa occurred. With few exceptions, maternal characteristics were similar between umbilical cord abnormality stillbirths and non-umbilical cord abnormality stillbirths and between umbilical cord abnormality stillbirths and live births, including among a subanalysis of those with hypo-coiled umbilical cords. CONCLUSION: Umbilical cord abnormalities are an important risk factor for stillbirth, accounting for 19% of cases, even when using rigorous criteria. Few specific maternal and clinical characteristics were associated with risk.


Assuntos
Natimorto/epidemiologia , Cordão Umbilical/anormalidades , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Estados Unidos/epidemiologia , Adulto Jovem
16.
Am J Perinatol ; 37(1): 59-65, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31491805

RESUMO

OBJECTIVE: We aimed to assess whether marijuana legalization was associated with a difference in prevalence of prenatal use or an increase in incidence of adverse perinatal outcomes. STUDY DESIGN: The present study is a retrospective cohort of September and October deliveries in the years 2012 through 2015 at a tertiary center in Colorado. Primary outcome of the study was use of marijuana, defined by self-report or biodetection. Secondary outcomes of the study included growth restriction, spontaneous preterm birth, stillbirth, preeclampsia, and neonatal or maternal death. Marijuana use prevalence was compared by year, and secondary outcomes between two periods, before and after the opening of the first recreational dispensary. RESULTS: A total of 2,392 pregnant women were included (1,165 before legalization and 1,227 after). More women used marijuana over the period of legalization (trend p = 0.01). Odds of marijuana use were higher after legalization versus before (adjusted odds ratio [aOR] = 1.8, 95% confidence interval [CI]: 1.2-2.6). Incidence of growth restriction was higher after legalization (2.9 vs. 5.1%, p = 0.0084). This difference persisted after adjustment for ethnicity and other drugs in multivariable modeling (aOR = 1.9, 95%CI: 1.2-3.0). CONCLUSION: The prevalence of prenatal marijuana use increased over the time of legalization. Further investigation into the population impact of legalization on obstetrical outcomes is warranted given the observed increase in growth restriction.


Assuntos
Retardo do Crescimento Fetal/epidemiologia , Uso da Maconha/legislação & jurisprudência , Colorado/epidemiologia , Anormalidades Congênitas/epidemiologia , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/diagnóstico por imagem , Humanos , Incidência , Recém-Nascido , Uso da Maconha/efeitos adversos , Uso da Maconha/tendências , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Prevalência , Estudos Retrospectivos , Natimorto/epidemiologia , Detecção do Abuso de Substâncias , Ultrassonografia Pré-Natal
17.
Am J Perinatol ; 37(12): 1223-1227, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31238345

RESUMO

OBJECTIVE: Substance use disorders often coexist with depression. The objective of this study was to establish whether pregnant women who report depressive symptomatology were more likely to report use of alcohol, tobacco, and marijuana during pregnancy. STUDY DESIGN: This was a secondary analysis of prospectively collected data from the Maternal-Fetal Medicine Units Network Preterm Prediction Study. Self-reported history of alcohol, tobacco, and marijuana use was compared between pregnant women with and without depressive symptomatology with adjustment for demographic factors. RESULTS: After adjustment for demographic factors, women with depressive symptomatology were more likely to report: any alcohol use (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 1.1-1.8), >1 drink per week (OR: 1.3, 95% CI: 1.0-1.8), and >1 drink per day (OR: 2.2, 95% CI: 1.5-3.4). Women with depressive symptomatology were also more likely to report use of marijuana (OR: 1.8, 95% CI: 1.2-2.6) and cigarettes (OR: 1.4, 95% CI: 1.1-1.7). CONCLUSION: Depressive symptomatology was associated with an increase in self-reported the use of alcohol, tobacco, and marijuana during pregnancy. These data reveal the importance of targeted screening of pregnant women with depressive symptomatology for substance use.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Depressão/epidemiologia , Uso da Maconha/epidemiologia , Uso de Tabaco/epidemiologia , Adulto , Colorado/epidemiologia , Feminino , Humanos , Modelos Logísticos , Gravidez , Autorrelato , Adulto Jovem
18.
J Matern Fetal Neonatal Med ; 33(19): 3318-3323, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30651010

RESUMO

Purpose: Perinatal antibiotic exposure may be associated with changes in both early infancy gut microbiota and later childhood obesity. Our objective was to evaluate if group B Streptococcus (GBS) antibiotic prophylaxis is associated with higher body mass index (BMI) in early childhood.Materials and methods: This is a retrospective cohort study of mother/child dyads in a single hospital system over a 6-year period. All women with term, singleton, vertex, vaginal deliveries who received no antibiotics or received antibiotics only for GBS prophylaxis and whose children had BMIs available at 2-5 years of age were included. Children were divided into three groups for comparison: children born to GBS positive mothers that received antibiotics solely for GBS prophylaxis, children born to GBS negative women that received no antibiotics (healthy controls), and children born to GBS positive mothers who received no antibiotics. The primary outcome was the earliest available child BMI Z-score at 2-5 years of age. Multivariable linear regression was used to estimate differences in child BMI Z-scores between groups, adjusted for maternal BMI, age, race, parity, tobacco use, and child birthweight.Results: Of 4825 women, 786 (16.3%) were GBS positive and received prophylactic antibiotics, 3916 (81.2%) were GBS negative and received no antibiotics, and 123 (2.5%) were GBS positive but received no antibiotics. Childhood BMI Z-scores were similar between children exposed to intrapartum GBS prophylaxis and healthy controls who were unexposed in both unadjusted (mean (SE), 0.04 (0.04) versus -0.3 (0.02), p = .11) and adjusted (0.01 (0.05) versus -0.04 (0.03), p = .3) models.Conclusions: Exposure to intrapartum antibiotic prophylaxis for GBS was not associated with higher early childhood BMI Z-scores compared to healthy controls.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Retrospectivos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae
19.
Birth ; 47(1): 123-134, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31823421

RESUMO

BACKGROUND: One approach to decreasing the cesarean birth rate in the United States is to increase the availability of birth attendants, including certified nurse-midwives (CNMs), who offer trial of labor after cesarean (TOLAC). We examined associations between provider type and mode of birth for women attempting vaginal birth after cesarean (VBAC). METHODS: We performed a retrospective cohort study at a United States academic medical center using prospectively-collected data (2005-2012). We included healthy women with term singleton vertex pregnancies after one or two prior cesareans who were managed by obstetricians or CNMs. We assessed unplanned cesarean birth by provider type using univariate and logistic regression and examined labor interventions and predicted VBAC success. RESULTS: Overall VBAC success was 88% for 502 included patients. Unplanned cesarean rates were similar by provider type. Black race, no prior VBAC, recurring clinical indication for cesarean, labor augmentation/induction, and any Pitocin use were associated with increased unplanned cesarean. Higher parity and early-term gestational age at delivery were associated with decreased unplanned cesarean. Postpartum hemorrhage and composite maternal morbidity were increased with unplanned cesarean, but there was no difference in neonatal outcome by mode of delivery or provider type. Obstetricians had slightly higher composite adverse maternal outcomes. Nomogram-predicted VBAC success but not provider type was associated with unplanned cesarean. CONCLUSIONS: Unplanned cesarean was similar for patients attempting labor after cesarean managed by midwives or obstetricians. Increasing the number of CNMs who manage TOLAC may help decrease the high rate of cesareans.


Assuntos
Ocitócicos/uso terapêutico , Ocitocina/uso terapêutico , Hemorragia Pós-Parto/etiologia , Prova de Trabalho de Parto , Nascimento Vaginal Após Cesárea/estatística & dados numéricos , Adolescente , Adulto , Colorado , Feminino , Idade Gestacional , Humanos , Início do Trabalho de Parto , Modelos Logísticos , Paridade , Hemorragia Pós-Parto/epidemiologia , Gravidez , Estudos Retrospectivos , Centros de Atenção Terciária , Nascimento Vaginal Após Cesárea/efeitos adversos , Adulto Jovem
20.
Obstet Gynecol ; 134(6): 1187-1196, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31764728

RESUMO

OBJECTIVE: To better characterize infection-related stillbirth in terms of pathogenesis and microbiology. METHODS: We conducted a secondary analysis of 512 stillbirths in a prospective, multisite, geographically, racially and ethnically diverse, population-based study of stillbirth in the United States. Cases underwent evaluation that included maternal interview, chart abstraction, biospecimen collection, fetal autopsy, and placental pathology. Recommended evaluations included syphilis and parvovirus serology. Each case was assigned probable and possible causes of death using the INCODE Stillbirth Classification System. Cases where infection was assigned as a probable or possible cause of death were reviewed. For these cases, clinical scenario, autopsy, maternal serology, culture results, and placental pathology were evaluated. RESULTS: For 66 (12.9%) cases of stillbirth, infection was identified as a probable or possible cause of death. Of these, 36% (95% CI 35-38%) were categorized as a probable and 64% (95% CI 62-65%) as a possible cause of death. Infection-related stillbirth occurred earlier than non-infection-related stillbirth (median gestational age 22 vs 28 weeks, P=.001). Fetal bacterial culture results were available in 47 cases (71%), of which 35 (53%) grew identifiable organisms. The predominant species were Escherichia coli (19, 29%), group B streptococcus (GBS) (8, 12%), and enterococcus species (8, 12%). Placental pathology revealed chorioamnionitis in 50 (76%), funisitis in 27 (41%), villitis in 11 (17%), deciduitis in 35 (53%), necrosis in 27 (41%), and viral staining in seven (11%) cases. Placental pathology found inflammation or evidence of infection in 65 (99%) cases and fetal autopsy in 26 (39%) cases. In infection-related stillbirth cases, the likely causative nonbacterial organisms identified were parvovirus in two (3%) cases, syphilis in one (2%) case, cytomegalovirus (CMV) in five (8%) cases, and herpes in one (2%) case. CONCLUSION: Of infection-related stillbirth cases in a large U.S. cohort, E coli, GBS, and enterococcus species were the most common bacterial pathogens and CMV the most common viral pathogen.


Assuntos
Complicações Infecciosas na Gravidez/mortalidade , Natimorto/epidemiologia , Adulto , Causas de Morte , Estudos de Coortes , Infecções por Citomegalovirus/etnologia , Infecções por Citomegalovirus/mortalidade , Demografia , Infecções por Escherichia coli/etnologia , Infecções por Escherichia coli/mortalidade , Feminino , Idade Gestacional , Humanos , Gravidez , Complicações Infecciosas na Gravidez/etnologia , Complicações Infecciosas na Gravidez/microbiologia , Cuidado Pré-Natal , Estudos Prospectivos , Fatores Socioeconômicos , Natimorto/etnologia , Estados Unidos/epidemiologia , Adulto Jovem
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