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1.
Eur J Obstet Gynecol Reprod Biol ; 266: 23-30, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34560330

RESUMO

OBJECTIVE: Our objective was to examine if US obstetrician-gynecologists (OBGYNs) practice outside of evidenced-based guidelines and use a combination of interventions to prevent spontaneous preterm birth (sPTB). STUDY DESIGN: An electronic survey was distributed to members of the Pregnancy-Related Care Research Network (PRCRN), and also to members of the Society of Maternal-Fetal Medicine (SMFM). The survey consisted of questions regarding physician demographics, and the use of interventions to prevent sPTB in women with 1) a prior sPTB, 2) an incidental short cervix (no prior sPTB), and 3) a history of cervical insufficiency. RESULTS: The PRCRN response rate was 58.6% (283/483) with an additional 143 responses from SMFM members. Among PRCRN responders, 82.7% were general OBGYNs and 17.3% were Maternal-Fetal Medicine subspecialists. Respondents were from all geographic regions of the country; most practiced in a group private practice (42.6%) or academic institution (31.4%). In women with prior sPTB, 45.2% of respondents would consider combination therapy, most commonly weekly intramuscular progesterone (IM-P) and serial cervical length (CL) measurements. If the patient then develops a short cervix, 33.7% would consider adding an ultrasound-indicated cerclage. In women with an incidental short cervix, 66.8% of respondents were likely to recommend single therapy with daily vaginal progesterone (VP). If a patient developed an incidentally dilated cervix, 40.8% of PRCRN respondents would recommend dual therapy, most commonly cerclage + VP, whereas 64.3% of SMFM respondents were likely to continue with VP only. In women with a history of cervical insufficiency, 47% of PRCRN respondents indicated they would consider a combination of IM-P, history-indicated cerclage and serial CL measurements. CONCLUSION: Although not currently supported by evidence-based medicine, combination therapy is commonly being used by U.S. OBGYNs to prevent sPTB in women with risk factors such as prior sPTB, short or dilated cervix or more than one of these risks.


Assuntos
Cerclagem Cervical , Nascimento Prematuro , Administração Intravaginal , Medida do Comprimento Cervical , Colo do Útero/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/prevenção & controle , Progesterona
2.
Epigenetics ; : 1-15, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34308756

RESUMO

Adverse pregnancy outcomes disproportionately affect non-Hispanic (NH) Black patients in the United States. Structural racism has been associated with increased psychosocial distress and inflammation and may trigger oxidative stress. Thus, the nitric oxide (NO) pathway (involved in the regulation of inflammation and oxidative stress) may partly explain the underlying disparities in obstetric outcomes.Cohort study of 154 pregnant patients with high-risk obstetric histories; n = 212 mRNAs and n = 108 microRNAs (miRNAs) in the NO pathway were evaluated in circulating white blood cells. NO pathway mRNA and miRNA transcript counts were compared by self-reported race; NH Black patients were compared with women of other races/ethnicities. Finally, miRNA-mRNA expression levels were correlated.Twenty-two genes (q < 0.10) were differentially expressed in self-identified NH Black individuals. Superoxide dismutase 1 (SOD1), interleukin-8 (IL-8), dynein light chain LC8-type 1 (DYNLL1), glutathione peroxidase 4 (GPX4), and glutathione peroxidase 1 (GPX1) were the five most differentially expressed genes among NH Black patients compared to other patients. There were 63 significantly correlated miRNA-mRNA pairs (q < 0.10) demonstrating potential miRNA regulation of associated target mRNA expression. Ten miRNAs that were identified as members of significant miRNA-mRNA pairs were also differentially expressed among NH Black patients (q < 0.10).These findings support an association between NO pathway and inflammation and infection-related mRNA and miRNA expression in blood drawn during pregnancy and patient race/ethnicity. These findings may reflect key differences in the biology of inflammatory gene dysregulation that occurs in response to the stress of systemic racism and that underlies disparities in pregnancy outcomes.

3.
Am J Obstet Gynecol MFM ; 3(5): 100414, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34082172

RESUMO

BACKGROUND: Communities and individuals widely vary in their resources and ability to respond to external stressors and insults. To identify vulnerable communities, the Centers for Disease Control and Prevention developed the Social Vulnerability Index, an integrated tool to assess community resources and preparedness; it is based on 15 factors and includes individual scores in the following 4 themes: socioeconomic status (theme 1), household composition and disability (theme 2), minority status and language (theme 3), and housing type and transportation (theme 4) and an overall composite score. Several Social Vulnerability Index components have been independently associated with an increased risk of preterm birth. OBJECTIVE: We sought to investigate the association of the Social Vulnerability Index for each patient's residence during pregnancy, personal clinical risk factors, and preterm birth. STUDY DESIGN: This was a retrospective cohort study of women carrying nonanomalous singleton or twin gestations delivering at a large university health system from April 2014 to January 2020. Women at high risk of spontaneous and medically indicated preterm birth were assigned to a census tract based on their geocoded home address, and a Social Vulnerability Index score was assigned to each individual by linking each patient's home address at the census tract level. Higher scores indicate greater social vulnerability. The primary outcome was preterm birth at <37 weeks' gestation; secondary outcomes were preterm birth at <34 and <28 weeks' gestation and composite major neonatal morbidity before initial hospital discharge (death, intraventricular leukomalacia or intraventricular hemorrhage, necrotizing enterocolitis, or bronchopulmonary dysplasia). Data were analyzed using the chi-square test, t test, and backward stepwise logistic regression. In addition, because race is a social construct, we conducted regression models omitting Black race. For all regression models, independent variables with a P value of <.20 remained in the final models. RESULTS: Overall, 15,364 women met the inclusion criteria, of which 18.5%, 6.5%, 2.1% of women delivered at <37, <34, and <28 weeks' gestation, respectively, and 3.1% of neonates were diagnosed with major composite morbidity. Women delivering before term at <37, <34, and <28 weeks' gestation were more likely to live in an area with a higher overall Social Vulnerability Index and higher social vulnerability in each Social Vulnerability Index theme. In regression models, the adjusted odds ratio of preterm birth increased with increasing Social Vulnerability Index scores (across all themes and the composite value); these effects were the greatest at the earliest gestational ages (eg, for the composite Social Vulnerability Index: adjusted odds ratio of preterm birth at <37 weeks' gestation for models, including Black race, 1.32 [95% confidence interval, 1.14-1.53]; adjusted odds ratio at <34 weeks' gestation, 1.60 [95% confidence interval, 1.27-2.01]; adjusted odds ratio at <28 weeks' gestation, 2.21 [95% confidence interval, 1.50-3.25]; adjusted odds ratio for composite major neonatal morbidity, 2.30 [95% confidence interval, 1.67-3.17]). Similar trends were seen for each Social Vulnerability Index theme. In addition, an increased adjusted odds ratio of composite major neonatal morbidity was recognized for each Social Vulnerability Index theme. Results were similar when Black race was removed from the models. CONCLUSION: The Social Vulnerability Index is a valuable tool that may further identify communities and individuals at the highest risk of preterm birth and may enable clinicians to integrate information regarding the local home environment of their patients to further refine preterm birth risk assessment.


Assuntos
Displasia Broncopulmonar , Nascimento Prematuro , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Gestantes , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos
4.
Am J Obstet Gynecol MFM ; 3(4): 100393, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33991707

RESUMO

BACKGROUND: There is an increased awareness regarding the association between exposure to environmental contaminants and adverse pregnancy outcomes including preterm birth. Whether an individual's metabolic profile can be utilized during pregnancy to differentiate the subset of patients who are ultimately destined to delivered preterm remains uncertain but could have MEANINGFUL clinical implications. OBJECTIVE: We sought to objectively quantify metabolomic profiles of patients at high risk of preterm birth by evaluating midtrimester maternal plasma and to measure whether endogenous metabolites and exogenous environmental substances differ among those who ultimately deliver preterm compared with those who deliver at term. STUDY DESIGN: This was a case-control analysis from a prospective cohort of patients carrying a singleton, nonanomalous gestation who were at high risk of spontaneous preterm birth. Subjects with a plasma blood sample drawn at <28 weeks' gestation and no evidence of preterm labor at the time of enrollment were included. Metabolites were extracted from frozen samples, and metabolomic analysis was performed using liquid chromatography/mass spectrometry. The primary outcome was preterm birth at 16.0 to 36.9 weeks' gestation. RESULTS: A total of 42 patients met the inclusion criteria. Of these, 25 (59.5%) delivered preterm at <37 weeks' gestation, at a median of 30.14 weeks' gestation (interquartile range, 28.14-34.14). A total of 812 molecular features differed between preterm birth cases and term controls with a minimum fold change of 1.2 and P<.05. Of these, 570 of 812 (70.1%) were found in higher abundances in preterm birth cases; the other 242 of 812 (29.9%) were in higher abundance in term birth controls. The identity of the small molecule/compound represented by the molecular features differing statistically between preterm birth cases and term controls was identified as ranging from those involved with endogenous metabolic pathways (including lipid catabolism, steroids, and steroid-related molecules) to exogenous exposures (including avocadyne, diosgenin, polycyclic aromatic hydrocarbons, acetaminophen metabolites, aspartame, and caffeine). Random forest analyses evaluating the relative contribution of each of the top 30 compounds in differentiating preterm birth and term controls accurately classified 21 of 25 preterm birth cases (84%). CONCLUSION: Both endogenous metabolites and exogenous exposures differ in maternal plasma in the midtrimester among patients who ultimately delivered preterm compared with those who deliver at term.


Assuntos
Trabalho de Parto Prematuro , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Policetídeos , Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos
6.
Epigenomics ; 13(9): 667-682, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33890487

RESUMO

Aim: The nitric oxide (NO) pathway modulates inflammation and may influence birth timing. Patients & methods: Case-control analysis of 136 pregnant women with RNA obtained <28 weeks; n = 212 mRNAs and n = 108 miRNAs in the NO pathway were evaluated. NO-pathway mRNA and miRNA transcript counts in women delivering preterm versus at term were compared, miRNA-mRNA expression levels correlated and prediction models generated. Results: Fourteen genes were differentially expressed in women delivering <37 weeks; 13/14 were also differentially expressed in those delivering <34 weeks (q <0.10) versus term births. Multiple miRNA-mRNA pairs were correlated. Models with gene expression better predicted prematurity than models with only clinical or nongenomic predictors. Conclusion: Maternal blood NO pathway-related mRNA and miRNA expression is associated with prematurity.

7.
Am J Obstet Gynecol MFM ; 3(4): 100353, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33757934

RESUMO

BACKGROUND: Non-Hispanic black maternal race is a known risk factor for preterm birth. However, the contribution of paternal race is not as well established. OBJECTIVE: We sought to evaluate the risk of preterm birth among non-Hispanic black, non-Hispanic white, and mixed non-Hispanic black and non-Hispanic white dyads. STUDY DESIGN: This was a population-based cohort study of all live births in the United States from 2015 to 2017, using live birth records from the National Vital Statistics System. Singleton, nonanomalous infants whose live birth record included maternal and paternal self-reported race as either non-Hispanic white or non-Hispanic black were included. The primary outcome was preterm birth at <37 weeks' gestation; secondary outcomes included preterm birth at <34 and <28 weeks' gestation and delivery gestational age (as a continuous variable). Data were analyzed using chi-square, t test, analysis of variance, and logistic regression. A Kaplan-Meier survival curve was also generated. RESULTS: There were 11,809,599 live births during the study period; 4,008,622 births met the inclusion criteria. Of included births, 291,647 (7.3%) occurred at <37 weeks' gestation. Using the convention of maternal race first followed by paternal race, preterm birth at <37 weeks' gestation was most common among non-Hispanic black and non-Hispanic black dyads (n=70,987 [10.8%]), followed by non-Hispanic black and non-Hispanic white (n=3137 [9.5%]), non-Hispanic white and non-Hispanic black (n=9136 [8.3%]), and non-Hispanic white and non-Hispanic white dyads (n=209,387 [6.5%]; P<.001 for trend). Births at <34 weeks' (n=74,474) and <28 weeks' gestation (n=18,474) were also more common among non-Hispanic black and non-Hispanic black dyads. Specifically, 24,351 (3.7%) non-Hispanic black and non-Hispanic black, 1017 (3.1%) non-Hispanic black and non-Hispanic white, 2408 (2.2%) non-Hispanic white and non-Hispanic black, and 46,698 non-Hispanic white and non-Hispanic white dyads delivered at <34 weeks' gestation, and 7988 non-Hispanic black and non-Hispanic black (1.2%), 313 (1.0%) non-Hispanic black and non-Hispanic white, 584 (0.5%) non-Hispanic white and non-Hispanic black, and 9589 (0.3%) non-Hispanic white and non-Hispanic white dyads delivered at <28 weeks' gestation. Non-Hispanic white and non-Hispanic white dyads delivered at a mean 38.8± standard deviation of 1.7 weeks' gestation, although non-Hispanic white and non-Hispanic black, non-Hispanic black and non-Hispanic white, and non-Hispanic black and non-Hispanic black dyads delivered at 38.6±2.0, 38.5±2.3, and 38.3±2.4 weeks' gestation, respectively (P<.001). Adjusted odds ratios for the association between maternal or paternal race and preterm birth were highest for non-Hispanic black and non-Hispanic black dyads at each gestational age cutoff: adjusted odds ratio, 1.60 (95% confidence interval, 1.11-1.19) (<37 weeks' gestation); adjusted odds ratio, 2.47 (95% confidence interval, 2.41-2.53) (<34 weeks' gestation); and adjusted odds ratio, 4.22 (95% confidence interval, 4.04-4.41) (<28 weeks' gestation) compared with the non-Hispanic white referent group. Models adjusted for insurance status, chronic hypertension, tobacco use during pregnancy, history of previous preterm birth, and male fetus. In the Kaplan-Meier survival analysis, non-Hispanic black and non-Hispanic black dyads delivered the earliest across the range of delivery gestational ages compared with all other combinations of dyads. CONCLUSION: Non-Hispanic black paternal race is a risk factor for preterm birth and should be considered when evaluating maternal a priori risk of prematurity. Future research should investigate the mechanisms behind this finding, including determining the contribution of factors, such as racism, maternal and paternal genetics, and epigenetics to an individual's risk of preterm birth.


Assuntos
Nascimento Prematuro , Estudos de Coortes , Pai , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Gravidez , Nascimento Prematuro/epidemiologia , Estados Unidos/epidemiologia
8.
Obstet Gynecol ; 137(4): 571-580, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33560778

RESUMO

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race-ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2-11%) incidence of venous thromboembolism among those with severe-critical illness compared with 0.2% in mild-moderate and 0% in asymptomatic (P<.001 for trend across severity). In adjusted analyses, severe-critical COVID-19 was associated with increased risk of cesarean birth (59.6% vs 34.0%, adjusted relative risk [aRR] 1.57, 95% CI 1.30-1.90), hypertensive disorders of pregnancy (40.4% vs 18.8%, aRR 1.61, 95% CI 1.18-2.20), and preterm birth (41.8% vs 11.9%, aRR 3.53, 95% CI 2.42-5.14) compared with asymptomatic patients. Mild-moderate COVID-19 was not associated with adverse perinatal outcomes compared with asymptomatic patients. CONCLUSION: Compared with pregnant patients with SARS-CoV-2 infection without symptoms, those with severe-critical COVID-19, but not those with mild-moderate COVID-19, were at increased risk of perinatal complications.


Assuntos
COVID-19/epidemiologia , Gravidade do Paciente , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Infecções Assintomáticas , Índice de Massa Corporal , COVID-19/complicações , COVID-19/diagnóstico , Cesárea/estatística & dados numéricos , Estudos de Coortes , Comorbidade , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido , Idade Materna , Mortalidade Materna , Mortalidade Perinatal , Gravidez , Complicações Infecciosas na Gravidez/virologia , Nascimento Prematuro/epidemiologia , Fatores de Risco , SARS-CoV-2 , Estados Unidos/epidemiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/virologia , Adulto Jovem
9.
Am J Obstet Gynecol MFM ; 3(3): 100308, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33444805

RESUMO

Preeclampsia and preterm birth are among the most common pregnancy complications and are the leading causes of maternal and fetal morbidity and mortality in the United States. Adverse pregnancy outcomes are multifactorial in nature and increasing evidence suggests that the pathophysiology behind preterm birth and preeclampsia may be similar-specifically, both of these disorders may involve abnormalities in placental vasculature. A growing body of literature supports that exposure to environmental contaminants in the air, water, soil, and consumer and household products serves as a key factor influencing the development of adverse pregnancy outcomes. In pregnant women, toxic metals have been detected in urine, peripheral blood, nail clippings, and amniotic fluid. The placenta serves as a "gatekeeper" between maternal and fetal exposures, because it can reduce or enhance fetal exposure to various toxicants. Proposed mechanisms underlying toxicant-mediated damage include disrupted placental vasculogenesis, an up-regulated proinflammatory state, oxidative stressors contributing to prostaglandin production and consequent cervical ripening, uterine contractions, and ruptured membranes and epigenetic changes that contribute to disrupted regulation of endocrine and immune system signaling. The objective of this review is to provide an overview of studies examining the relationships between environmental contaminants in the US setting, specifically inorganic (eg, cadmium, arsenic, lead, and mercury) and organic (eg, per- and polyfluoroalkyl substances) toxicants, and the development of preeclampsia and preterm birth among women in the United States.


Assuntos
Mercúrio , Pré-Eclâmpsia , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Placenta , Pré-Eclâmpsia/induzido quimicamente , Gravidez , Resultado da Gravidez , Nascimento Prematuro/induzido quimicamente , Estados Unidos/epidemiologia
11.
J Matern Fetal Neonatal Med ; 34(7): 1042-1047, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31170845

RESUMO

OBJECTIVE: To identify risk factors associated with neonatal intermediate or intensive care unit (NICU) stay ≥3 days among women with threatened late preterm birth (PTB). STUDY DESIGN: Secondary analysis of women with nonanomalous, singleton gestations enrolled in multicenter trial of betamethasone versus placebo for late PTB. Maternal and obstetric characteristics at time of presentation with threatened PTB were compared between those with and without NICU stay ≥3 days. Multivariable logistic regression identified risk factors for NICU stay ≥3 days. RESULT: Of 2795 eligible mother-neonate dyads, 962 (34%) had NICU stay ≥3 days. Gestational age and fetal growth restriction as the reason for threatened PTB had the strongest association with NICU stay ≥3 days in the final model (AUC 0.76). CONCLUSION: Maternal and obstetric characteristics at the time of admission for threatened late PTB should be considered when counseling patients about the probability of NICU stay ≥3 days.


Assuntos
Unidades de Terapia Intensiva Neonatal , Nascimento Prematuro , Betametasona , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Fatores de Risco
12.
Am J Obstet Gynecol MFM ; 2(3): 100104, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-33179010

RESUMO

Objectives: Despite persistent racial disparities in preterm birth (PTB) in the US among non-Hispanic (NH) black women compared to NH white women, it remains controversial whether sociodemographic factors can explain these differences. We sought to evaluate whether disparities in PTB persist among NH black women with high socioeconomic status (SES). Study Design: We conducted a population-based cohort study of all live births in the US from 2015-2017 using birth certificate data from the National Vital Statistics System. We included singleton, non-anomalous live births among women who were of high SES (defined as having ≥ 16 years of education, private insurance, and not receiving Women, Infants and Children [WIC] benefits) and who identified as NH white, NH black, or 'mixed' NH black and white race. The primary outcome was PTB <37 weeks; secondary outcomes included PTB <34 and <28 weeks. In addition, analyses were repeated considering birthweight <2500g as a surrogate for preterm birth <37 weeks, birthweight <1500g as a surrogate for preterm birth <34 weeks, and birthweight <750g as a surrogate for preterm birth <28 weeks' gestation. Data were analyzed with chi-square, t-test, and logistic regression. Results: 2,170,686 live births met inclusion criteria, with 92.9% NH white, 6.7% NH black, and 0.4% both NH white and black race. Overall, 5.9% delivered <37, 1.3% <34, and 0.3 % <28 weeks. In unadjusted analyses of women with high SES, the PTB rate at each gestational age cutoff was higher for women of 'mixed' NH white and black race, and highest for women who were NH black only compared to women who were NH white only. In regression models we further adjusted for women with insurance and prenatal care their entire pregnancy, maternal race was associated with higher odds of PTB at each GA cutoff, with the highest odds observed at <28 weeks. Finally, in further adjustement analysis including only the 1,934,912 women who received prenatal care in the first trimester, findings were similar. Rates of preterm birth at each gestational age cutoff remained highest for women who identified as non-Hispanic black, intermediate for women identifying as both non-Hispanic black and white race, and lowest for non-Hispanic white women at <37 weeks (9.9% vs. 6.1% vs. 5.5%, respectively; p<0.001), <34 weeks (3.5% vs. 1.5% vs. 1.1%, respectively; p<0.001), and <28 weeks' gestation (1.2% vs. 0.4% vs. 0.2%, respectively, p<0.001). Conclusions: Even among college-educated women with private insurance who are not receiving WIC, racial disparities in prematurity persist. These national findings are consistent with prior studies that suggest factors other than socio-demographics are important in the underlying pathogenesis of PTB.


Assuntos
Nascimento Prematuro , Criança , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Classe Social
13.
Am J Obstet Gynecol MFM ; 2(1): 100077, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32905377

RESUMO

Background: Antenatal corticosteroids reduce morbidity and mortality among preterm neonates. However, the optimal timing of steroid administration with regards to severe neonatal and early childhood morbidity is uncertain. Objective: To evaluate the association between the timing of antenatal corticosteroid adminstration and preterm outcomes. We hypothesized that neonates exposed to antenatal corticosteroids 2 to <7 days before delivery would have the lowest risks of neonatal and childhood morbidity. Study Design: Secondary analysis of two prospective multicenter studies enriched for spontaneous preterm birth, Genomics and Proteomics Network for Preterm Birth Research (11/2007-1/2011) and Beneficial Effect of Antenatal Magnesium (12/1997-5/2004). We included women with singleton gestations who received antenatal corticosteroids and delivered at 23 0/7-33 6/7 weeks' gestation. Women who received ≥1 course of corticosteroids were excluded. Neonatal outcomes were compared by the timing of the first dose of antenatal corticosteroids in relation to delivery: <2 days, 2 to <7 days, 7 to <14 days, and ≥14 days. The primary outcome was respiratory distress syndrome. Secondary outcomes included composite neonatal morbidity (death, intraventricular hemorrhage grade III or IV, periventricular leukomalacia, bronchopulmonary dysplasia, or necrotizing enterocolitis), and early childhood morbidity (death or moderate to severe cerebral palsy at age 2). Multivariable logistic regression estimated the association between timing of antenatal corticosteroid administration and study outcomes. Results: A total of 2,259 subjects met inclusion criteria: 622 (27.5%) received antenatal corticosteroids <2 days before delivery, 821 (36.3%) 2 to <7 days, 401 (17.8%) 7 to <14 days, and 415 (18.4%) ≥14 days. The majority (78.1%) delivered following idiopathic spontaneous preterm labor or preterm premature rupture of membranes at a mean gestational age of 29.5 +/-2.8 weeks. Neonates exposed to antenatal corticosteroids 2 to <7 days before delivery were the least likely to develop respiratory distress syndrome (51.3%), compared to those receiving antenatal corticosteroids <2 days, 7 to <14 days, and ≥14 days before delivery (62.7%, 55.9%, and 57.6%, respectively, p<0.001). Compared to receipt 2 to <7 days before delivery, there was an increased odds of respiratory distress syndrome with receipt of antenatal corticosteroids <2 days (aOR 2.07, 95%CI 1.61-2.66), 7 to <14 days (aOR 1.40, 95% CI 1.07-1.83), and ≥14 days (aOR 2.34, 95%CI 1.78-3.07). Neonates exposed to antenatal corticosteroids ≥14 days before delivery were at increased odds for severe neonatal morbidity (aOR 1.57, 95%CI 1.12-2.19) and early childhood morbidity (aOR 1.74, 95%CI 1.02-2.95), compared to those exposed 2 to <7 days before delivery. There was no significant association between antenatal corticosteroid receipt <2 days or 7 to <14 days and severe neonatal morbidity or severe childhood morbidity. Conclusions: Preterm neonates exposed to antenatal corticosteroids 2 to <7 days before delivery had the lowest odds of respiratory distress syndrome, compared to shorter and longer time intervals between steroid administration and delivery. Antenatal corticosteroid administration ≥14 days before delivery is associated with an increased odds of severe neonatal and childhood morbidity, compared to 2 to <7 days before delivery. These results emphasize the importance of optimally timed antenatal corticosteroids to improve both short- and long-term outcomes.


Assuntos
Nascimento Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido , Corticosteroides/efeitos adversos , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Nascimento Prematuro/tratamento farmacológico , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia
14.
Am J Obstet Gynecol MFM ; 2(4): 100229, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32995736

RESUMO

Both acute and chronic stress can cause allostatic overload, or long-term imbalance in mediators of homeostasis, that results in disruptions in the maternal-placental-fetal endocrine and immune system responses. During pregnancy, disruptions in homeostasis may increase the likelihood of preterm birth and preeclampsia. Expectant mothers traditionally have high rates of anxiety and depressive disorders, and many are susceptible to a variety of stressors during pregnancy. These common life stressors include financial concerns and relationship challenges and may be exacerbated by the biological, social, and psychological changes occurring during pregnancy. In addition, external stressors such as major weather events (eg, hurricanes, tornados, floods) and other global phenomena (eg, the coronavirus disease 2019 pandemic) may contribute to stress during pregnancy. This review investigates recent literature published about the use of nonpharmacologic modalities for stress relief in pregnancy and examines the interplay between psychiatric diagnoses and stressors, with the purpose of evaluating the feasibility of implementing nonpharmacologic interventions as sole therapies or in conjunction with psychotherapy or psychiatric medication therapy. Further, the effectiveness of each nonpharmacologic therapy in reducing symptoms of maternal stress is reviewed. Mindfulness meditation and biofeedback have shown effectiveness in improving one's mental health, such as depressive symptoms and anxiety. Exercise, including yoga, may improve both depressive symptoms and birth outcomes. Expressive writing has successfully been applied postpartum and in response to pregnancy challenges. Although some of these nonpharmacologic interventions can be convenient and low cost, there is a trend toward inconsistent implementation of these modalities. Future investigations should focus on methods to increase ease of uptake, ensure each option is available at home, and provide a standardized way to evaluate whether combinations of different interventions may provide added benefit.


Assuntos
COVID-19 , Terapias Complementares/métodos , Complicações na Gravidez , Resultado da Gravidez/epidemiologia , Psicoterapia/métodos , Estresse Psicológico , COVID-19/epidemiologia , COVID-19/psicologia , Feminino , Humanos , Recém-Nascido , Saúde Mental , Gravidez , Complicações na Gravidez/psicologia , Complicações na Gravidez/terapia , SARS-CoV-2 , Estresse Psicológico/etiologia , Estresse Psicológico/terapia
15.
Am J Obstet Gynecol MFM ; 2(2): 100108, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32835205

RESUMO

Objective: tExtracorporeal membrane oxygenation (ECMO) is a life-saving therapy for severe, reversible cardiopulmonary failure, but data regarding its use in pregnancy and the postpartum period are limited. We sought to quantify survival of pregnant and postpartum women necessitating ECMO in a contemporary cohort at a single tertiary institution. Study Design: All women of reproductive age (14-44 years), who underwent ECMO at our institution between January 1, 2008, and December 31, 2017, were identified using a query of hospital encounters for ECMO-related CPT codes. We manually reviewed all charts of women of reproductive age; women who were pregnant or <6 weeks postpartum at the time of ECMO initiation were included. Clinical characteristics and maternal and fetal outcomes are described. Results: In this study, 54 women of reproductive age underwent ECMO for cardiopulmonary failure. Of those, 9 (17%) were pregnant or <6 weeks postpartum at the time of ECMO initiation: 4 antepartum, 1 intraoperative at the time of cesarean delivery, and 4 postpartum (including 2 in whom ECMO was initiated on postpartum day 0 or 1). Overall, maternal survival was 33%. The median maternal age was 24 years (range 19-39 years); most women were nonsmokers without underlying medical comorbidities. The most common indication for ECMO use in pregnant and postpartum women was acute respiratory distress syndrome, which was present in 7 cases (78%), including 5 cases that were due to infectious etiologies and 2 cases that were attributed to preeclampsia. The median number of days on ECMO was 6 (range 1-14). There were no cases of obstetric hemorrhage. Venovenous ECMO was utilized in all but 1 case, in which emergent attempted venoarterial ECMO was unsuccessful in resuscitating a postpartum patient with cardiac arrest and a massive pulmonary embolism. A total of 4 women were initiated on ECMO during pregnancy: their gestational ages at ECMO initiation were 21, 22, 29, and 30 weeks; maternal survival was 50%, and fetal mortality was 50%. A case of ECMO initiated during cesarean section at 29 weeks' gestation resulted in both maternal and fetal survival. Among 4 mothers with ECMO initiation after childbirth, none survived. Finally, we found a tendency toward survival in those patients for whom ECMO was initiated soon after mechanical ventilation, earlier in the disease process. In contrast, in this study, 23 of 45 women of reproductive age (51%) who were not pregnant but underwent ECMO survived. Conclusion: When ECMO was initiated during pregnancy or during childbirth, 60% of mothers and fetuses survived, supporting current use of ECMO as a salvage therapy in pregnant and intrapartum women. In this generally young and healthy population, ECMO has the potential to increase the survival rates of both mother and fetus and should be considered a salvage therapy for peripartum women with reversible forms of cardiorespiratory failure.


Assuntos
Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Adolescente , Adulto , Cesárea , Feminino , Humanos , Período Pós-Parto , Gravidez , Insuficiência Respiratória/terapia , Adulto Jovem
16.
J Womens Health (Larchmt) ; 29(12): 1559-1563, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32678995

RESUMO

Background: Screening for diabetes in early pregnancy is recommended for high-risk women, however, the optimal test for the diagnosis of early gestational diabetes mellitus (GDM) is unknown. Thus, the objective of this study was to evaluate hemoglobin A1c (HbA1c) as a diagnostic test for early GDM compared with two-step testing. Materials and Methods: Retrospective cohort of women with prior GDM or obesity who had HbA1c and two-step testing <21 weeks' gestation. Early GDM was diagnosed by 1 hour, 50 g oral glucose challenge test (GCT) ≥135 mg/dL and ≥2 abnormal values on 3 hour, 100 g oral glucose tolerance test or GCT >200 mg/dL. The area under the receiver operating characteristic curve (AUC) evaluated HbA1c for diagnosis of early GDM. Results: Of 243 women, 14 (5.8%) had early GDM by two-step testing. Median HbA1c levels were higher among women with GDM versus those without GDM (5.8% vs. 5.3%, p < 0.001). The AUC for HbA1c compared with two-step testing was 0.80 (95% CI 0.69-0.91). The optimal HbA1c threshold was 5.6% (64% sensitivity, 84% specificity). Conclusions: HbA1c is moderately predictive of early GDM compared with two-step testing, and a threshold lower than that used for diabetes diagnosis among nonpregnant adults is justified.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/diagnóstico , Hemoglobina A Glicada/análise , Adulto , Biomarcadores/sangue , Glicemia/análise , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Feminino , Teste de Tolerância a Glucose , Humanos , Obesidade/epidemiologia , Valor Preditivo dos Testes , Gravidez , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Am J Obstet Gynecol MFM ; 2(2): 100110, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32518901

RESUMO

This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation; and provide specific guidance for management of L&D of the COVID-19-positive woman, as well as the critically ill COVID-19-positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19-positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19-positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities.


Assuntos
COVID-19/prevenção & controle , Parto Obstétrico/métodos , Cuidado Pós-Natal/métodos , Guias de Prática Clínica como Assunto , Complicações Infecciosas na Gravidez/prevenção & controle , Fluxo de Trabalho , Anestesia Epidural/métodos , Anestesia Obstétrica/métodos , COVID-19/diagnóstico , COVID-19/terapia , Estado Terminal , Feminino , Humanos , Trabalho de Parto Induzido/métodos , Trabalho de Parto , Tempo de Internação , Programas de Rastreamento , Alta do Paciente , Isolamento de Pacientes , Equipamento de Proteção Individual , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , SARS-CoV-2 , Triagem/métodos
18.
Environ Sci Technol ; 54(13): 8158-8166, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32469207

RESUMO

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS), a ubiquitous class of chemicals, is associated with adverse outcomes such as pre-eclampsia, low infant birth weight, and later-life adiposity. The objectives of this study were to examine PFAS levels in the placenta and identify sociodemographic risk factors in a high-risk pregnancy cohort (n = 122) in Chapel Hill, North Carolina. Of concern, PFOS, PFHxS, PFHpS, and PFUnA were detected above the reporting limit in 99, 75, 55, and 49% of placentas, respectively. Maternal race/ethnicity was associated with significant differences in PFUnA levels. While the data from this high-risk cohort did not provide evidence for an association with hypertensive disorders of pregnancy, fetal growth, or gestational age, the prevalence of detectable PFAS in the placenta suggests a need to biomonitor for exposure to PFAS during pregnancy. Future research should investigate factors underlying the differences in PFAS levels in association with a mother's race/ethnicity, as well as potential effects on pregnancy and child health.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorcarbonetos , Criança , Feminino , Fluorcarbonetos/análise , Humanos , Lactente , North Carolina , Placenta/química , Gravidez , Gravidez de Alto Risco , Fatores de Risco
19.
Reprod Toxicol ; 98: 1-12, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061676

RESUMO

Environmental chemicals comprise a major portion of the human exposome, with some shown to impact the health of susceptible populations, including pregnant women and developing fetuses. The placenta and cord blood serve as important biological windows into the maternal and fetal environments. In this article we review how environmental chemicals (defined here to include man-made chemicals [e.g., flame retardants, pesticides/herbicides, per- and polyfluoroalkyl substances], toxins, metals, and other xenobiotic compounds) contribute to the prenatal exposome and highlight future directions to advance this research field. Our findings from a survey of recent literature indicate the need to better understand the breadth of environmental chemicals that reach the placenta and cord blood, as well as the linkages between prenatal exposures, mechanisms of toxicity, and subsequent health outcomes. Research efforts tailored towards addressing these needs will provide a more comprehensive understanding of how environmental chemicals impact maternal and fetal health.

20.
Drug Metab Dispos ; 48(4): 264-271, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31980499

RESUMO

This study's primary objective was to fully characterize the pharmacokinetics of metformin in pregnant women with gestational diabetes mellitus (GDM) versus nonpregnant controls. Steady-state oral metformin pharmacokinetics in pregnant women with GDM receiving either metformin monotherapy (n = 24) or a combination with glyburide (n = 30) as well as in nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 24) were determined utilizing noncompartmental techniques. Maternal and umbilical cord blood samples were collected at delivery from 38 women. With both 500- and 1000-mg doses, metformin bioavailability, volume of distribution beta (V ß ), clearance, and renal clearance were significantly increased during pregnancy. In addition, in the women receiving metformin 500 mg, significantly higher metformin apparent oral clearance (CL/F) (27%), weight-adjusted renal secretion clearance (64%), and apparent oral volume of distribution beta (V ß /F) (33%) were seen during pregnancy. Creatinine clearance was significantly higher during pregnancy. Increasing metformin dose from 500 to 1000 mg orally twice daily significantly increased V ß /F by 28%, weight-adjusted V ß /F by 32% and CL/F by 25%, and weight-adjusted CL/F by 28% during pregnancy. Mean metformin umbilical cord arterial-to-venous plasma concentration ratio was 1.0 ± 0.1, venous umbilical cord-to-maternal concentration ratio was 1.4 ± 0.5, and arterial umbilical cord-to-maternal concentration ratio was 1.5 ± 0.5. Systemic exposure after a 500-mg dose of metformin was lower during pregnancy compared with the nonpregnant women with T2DM. However, in patients receiving metformin 1000 mg, changes in estimated bioavailability during pregnancy offset the changes in clearance leading to no significant change in CL/F with the higher dose. SIGNIFICANCE STATEMENT: Gestational diabetes mellitus complicates 5%-13% of pregnancies and is often treated with metformin. Pregnant women undergo physiological changes that alter drug disposition. Preliminary data suggest that pregnancy lowers metformin concentrations, potentially affecting efficacy and safety. This study definitively describes pregnancy's effects on metformin pharmacokinetics and expands the mechanistic understanding of pharmacokinetic changes across the dosage range. Here we report the nonlinearity of metformin pharmacokinetics and the increase in bioavailability, clearance, renal clearance, and volume of distribution during pregnancy.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/farmacocinética , Metformina/farmacocinética , Adolescente , Adulto , Disponibilidade Biológica , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Diabetes Gestacional/sangue , Diabetes Gestacional/urina , Relação Dose-Resposta a Droga , Feminino , Sangue Fetal , Humanos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Eliminação Renal , Adulto Jovem
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