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1.
Pediatr Dev Pathol ; : 10935266241259346, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907667

RESUMO

BACKGROUND: Placental maternal vascular malperfusion (MVM) is characterized by accelerated villous maturation and has been associated with a decrease in the antiaging protein, alpha-klotho (AK). Our aim was to characterize AK protein and gene expression in the placenta and fetal organs. METHODS: We utilized 2 cohorts. First, we characterized AK protein expression in an autopsy cohort where cases were defined as MVM as the cause of fetal death compared to a stillborn control population. Second, we characterized placental and umbilical cord blood AK gene expression in a liveborn population with and without MVM. RESULTS: We found decreased protein expression in the villous trophoblastic cells of placentas exposed to severe MVM and decreased AK gene expression in placental tissue exposed to MVM. We did not see any statistically significant differences in fetal organ or umbilical cord blood AK expression based on the presence or absence of MVM. Furthermore, in liveborn infants, we also found increased odds of preterm birth with lower placental AK expression. CONCLUSIONS: Decreased AK gene and protein expression in the placenta in the setting of MVM is consistent with the theory of placental aging in MVM and is associated with increased odds of preterm birth.

2.
J Perinatol ; 44(1): 46-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37700009

RESUMO

OBJECTIVE: To identify bacteria in umbilical cord tissue and investigate the association with placental inflammation and neonatal sepsis risk score. STUDY DESIGN: Retrospective cohort study from 2017-2019. RNA was extracted from umbilical cord tissue and NanoString nCounter used to identify seven bacteria genera. Sepsis risk score was calculated using the Kaiser sepsis calculator. Placental histopathology was abstracted from medical records. RESULTS: Detection of bacterial RNA in the umbilical cord (n = 96/287) was associated with high-stage maternal and fetal acute placental inflammation (maternal 35.4% vs 22.5%, p = 0.03 and fetal 34.4% vs 19.4%, p < 0.01) and maternal vascular malperfusion (36.5% vs 23.0%, p = 0.02). Detection of Ureaplasma spp. was also associated with increased sepsis risk score (1.5/1000 [0.6, 8.6] vs 0.9/1000 [0.2, 2.9], p = 0.04). CONCLUSION: Umbilical cord bacterial pathogens are linked to fetal and maternal placental inflammation and maternal vascular malperfusion during gestation and associated with increased sepsis risk score in the neonate.


Assuntos
Sepse Neonatal , Sepse , Recém-Nascido , Gravidez , Feminino , Humanos , Placenta/patologia , Sepse Neonatal/diagnóstico , Estudos Retrospectivos , Bactérias , Inflamação
3.
Am J Obstet Gynecol ; 230(4): 452.e1-452.e11, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37751829

RESUMO

BACKGROUND: Spontaneous preterm birth significantly increases the risk for a recurrent preterm birth. Only a few identifiable clinical risk factors can be referenced in counseling for recurrent preterm birth. Furthermore, treatment using progesterone supplementation has not consistently prevented preterm birth among high-risk patients, but it may be effective in a subset of those patients. Placental pathology from a previous pregnancy may be used to predict which patients will experience a recurrent preterm birth or to identify a subset of patients more likely to respond to treatment with antenatal progesterone. OBJECTIVE: This study aimed to determine if histologic patterns are associated with recurrent preterm birth among patients with an index spontaneous preterm birth. A secondary objective was to determine if placental histologic types and/or progesterone receptor density in the decidua are associated with the response to progesterone supplementation with intramuscular 17-hydroxyprogesterone caproate. STUDY DESIGN: This was a retrospective cohort study at a single institution of women with singleton pregnancies with an index spontaneous preterm birth and a subsequent birth within the same hospital system between 2009 and 2019. Patients were included if placental pathology was available for the index spontaneous preterm birth. A logistic regression was used to determine if there were independent associations between 4 histologic types (acute inflammation, maternal vascular malperfusion, fetal vascular malperfusion, chronic inflammation) and recurrent preterm birth. For the secondary endpoint, 17-hydroxyprogesterone caproate response was defined as prolonging gestation by >3 weeks beyond the gestational age at delivery in the index pregnancy. Patients who delivered <3 weeks beyond the gestational age in the index pregnancy but at ≥39 weeks' gestation were excluded. A logistic regression was used to assess the independent association between placental histology and 17-hydroxyprogesterone caproate response. Sensitivity analyses were completed using only patients with an index birth <36 weeks' gestation, and then excluding those with medically indicated preterm birth in a subsequent pregnancy. A nested case-control immunohistochemical study was done among 20 patients with a subsequent term birth and 20 patients with a subsequent spontaneous preterm birth. The percentage of cells in the maternal decidua positive for progesterone receptors was correlated with the subsequent pregnancy outcome. RESULTS: A total of 352 patients were included. Acute inflammation was the most common histologic type seen among patients with spontaneous preterm birth (44.1%), followed by chronic inflammation (40.9%) and maternal vascular malperfusion (31.3%). No histologic type was independently associated with recurrent preterm birth. A total of 155 patients received 17-hydroxyprogesterone caproate in a second pregnancy. Low-grade acute inflammation was significantly associated with a decreased likelihood of 17-hydroxyprogesterone caproate response. Low-grade maternal vascular malperfusion among those with an index pregnancy delivered at <36 weeks' gestation was significantly associated with a more than 4 times increased likelihood of 17-hydroxyprogesterone caproate response when excluding those with a subsequent iatrogenic preterm birth. Progesterone receptor staining was not associated with recurrent preterm birth. CONCLUSION: Although acute inflammation was prevalent among spontaneous preterm births, more than half of the spontaneous preterm births were not associated with acute inflammation. Low-grade acute inflammation was associated with a significantly decreased response to 17-hydroxyprogesterone caproate supplementation. Low-grade maternal vascular malperfusion was associated with a 4-fold increased likelihood of 17-hydroxyprogesterone caproate response among those with index deliveries <36 weeks' gestation. Further work is needed to determine if placental pathologic examination can be used to target treatment in subsequent pregnancies to prevent recurrent preterm birth.


Assuntos
Hidroxiprogesteronas , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Lactente , Caproato de 17 alfa-Hidroxiprogesterona , Hidroxiprogesteronas/uso terapêutico , Progesterona , Receptores de Progesterona , Nascimento Prematuro/prevenção & controle , Estudos Retrospectivos , Placenta , 17-alfa-Hidroxiprogesterona , Medição de Risco , Número de Gestações , Inflamação/tratamento farmacológico
4.
Am J Obstet Gynecol MFM ; 5(12): 101200, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37875178

RESUMO

BACKGROUND: Racial and socioeconomic disparities in preterm birth and small for gestational age births are growing in the United States, increasing the burden of morbidity and mortality particularly among Black women and birthing persons and their infants. Group prenatal care is one of the only interventions to show potential to reduce the disparity, but the mechanism is unclear. OBJECTIVE: The goal of this project was to identify if group prenatal care, when compared with individual prenatal care, was associated with a reduction in systemic inflammation during pregnancy and a lower prevalence of inflammatory lesions in the placenta at delivery. STUDY DESIGN: The Psychosocial Intervention and Inflammation in Centering Study was a prospective cohort study that exclusively enrolled participants from a large randomized controlled trial of group prenatal care (the Cradle study, R01HD082311, ClinicalTrials.gov: NCT02640638) that was performed at a single site in Greenville, South Carolina, from 2016 to 2020. In the Cradle study, patients were randomized to either group prenatal care or individual prenatal care, and survey data were collected during the second and third trimesters. The Psychosocial Intervention and Inflammation in Centering Study cohort additionally provided serum samples at these 2 survey time points and permitted collection of placental biopsies for inflammatory and histologic analysis, respectively. We examined associations between group prenatal care treatment and a composite of z scored serum inflammatory biomarkers (C-reactive protein, interleukin-6, interleukin-1 receptor antagonist, interleukin-10, and tumor necrosis factor α) in both the second and third trimesters and the association with the prevalence of acute and chronic maternal placental inflammatory lesions. Analyses were conducted using the intent to treat principle, and the results were also examined by attendance of visits in the assigned treatment group (modified intent to treat and median or more number of visits) and were stratified by race and ethnicity. RESULTS: A total of 1256 of 1375 (92%) Cradle participants who were approached enrolled in the Psychosocial Intervention and Inflammation in Centering Study, which included 54% of all the Cradle participants. The Psychosocial Intervention and Inflammation in Centering Study cohort did not differ from the Cradle cohort by demographic or clinical characteristics. Among the 1256 Psychosocial Intervention and Inflammation in Centering Study participants, 1133 (89.6%) had placental data available for analysis. Among those, 549 were assigned to group prenatal care and 584 of 1133 were assigned to individual prenatal care. In the intent to treat and modified intent to treat cohorts, participation in group prenatal care was associated with a higher serum inflammatory score, but it was not associated with an increased prevalence of placental inflammatory lesions. In the stratified analyses, group prenatal care was associated with a higher second trimester inflammatory biomarker composite (modified intent to treat: B=1.17; P=.02; and median or more visits: B=1.24; P=.05) among Hispanic or Latine participants. CONCLUSION: Unexpectedly, group prenatal care was associated with higher maternal serum inflammation during pregnancy, especially among Hispanic or Latine participants.


Assuntos
Placenta , Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Estados Unidos , Placenta/patologia , Cuidado Pré-Natal , Estudos Prospectivos , Inflamação/diagnóstico , Inflamação/epidemiologia , Inflamação/patologia
5.
Am J Surg Pathol ; 47(10): 1116-1121, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37545349

RESUMO

Placental examination, frequently performed by general surgical pathologists, plays an important role in understanding patient outcomes and explaining the underlying mechanisms leading to preterm birth (PTB). This secondary analysis of a larger study recurrent PTB aimed to compare diagnoses between general surgical pathologists (GSP) and a perinatal pathologist (PP) in preterm placentas examined between 2009 and 2018 at a single institution. Pathology diagnoses were coded into 4 categories (acute inflammation [AI], chronic inflammation, fetal vascular malperfusion, maternal vascular malperfusion) based on original reports for the GSP and second review by the single PP. A total of 331 placentas were included, representing placentas finalized by 17 GSPs. The prevalence of all 4 placental diagnostic categories was higher for the PP, and nearly half (49.2%) of placentas finalized by GSP had no diagnostic findings. Agreement was highest for AI at κ=0.50 (weak agreement). However, there was no agreement for maternal vascular malperfusion (κ=0.063), chronic inflammation (κ=0.0026), and fetal vascular malperfusion (κ = -0.018). Chronic basal deciduitis with plasma cells had the highest false-negative rate (missed in 107 cases by GSP). Villous infarction had the highest false-positive rate (overcalled in 28/41 [68%] cases) with the majority of the "infarcts" representing intervillous thrombi. In conclusion, there is no agreement between GSP and PP when assessing placental pathology other than AI, and weak agreement even for AI. These findings are a call to action to implement educational efforts and structural/organizational changes to improve consistency of placental pathology reporting.


Assuntos
Placenta , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Placenta/patologia , Nascimento Prematuro/patologia , Patologistas , Inflamação/patologia
6.
Pediatr Dev Pathol ; 26(5): 458-465, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37599445

RESUMO

BACKGROUND: The histopathology and CD15 expression in large for gestational age (LGA) placentas is not well-documented. METHODS: To analyze this, we utilized 2 separate cohorts of placentas from singleton term deliveries. LGA and appropriate for gestational age (AGA) placentas were compared for major histopathologies including acute and chronic inflammation, maternal and fetal vascular malperfusion, delayed villous maturation (DVM), and villous hypervascularity/chorangiosis. We also examined CD15 immunohistochemistry in LGA and AGA placentas. Stained slides were reviewed blinded to the placental weight. Five random 20× fields were scored semi-quantitatively for CD15 staining of villous capillaries on a scale of 0 to 5 (0 = 0%, 1 = 1%-5%, 2 = 5%-25%, 3 = 25%-50%, 4 = 50%-75%, and 5 = >75%). RESULTS: In 1 cohort, 1238 LGA and 7908 AGA placentas were identified. Patients with LGA placentas were significantly more likely to have higher birthweight babies, obesity, hypertensive disorders, pre-gestational, and gestational diabetes. Also, LGA placentas had a higher prevalence of fetal vascular malperfusion, DVM, and villous chorangiosis. In other cohort of 75 LGA placentas and 73 AGA controls, the average score of CD15 staining in villous capillaries was significantly higher amongst LGA placentas. CONCLUSION: We conclude that LGA placentas have increased expression of CD15 in villous capillary endothelium and higher prevalence of FVM, DVM, and villous chorangiosis than AGA placentas.


Assuntos
Placenta , Gravidez , Humanos , Feminino , Placenta/patologia , Idade Gestacional , Imuno-Histoquímica , Peso ao Nascer
7.
Placenta ; 139: 85-91, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37336159

RESUMO

INTRODUCTION: Maternal vascular malperfusion (MVM) is commonly observed in early onset preeclampsia, but less prevalent in late onset preeclampsia. The purpose of our analysis was to investigate patterns of placental pathology in preeclampsia. METHODS: Electronic health records for all singleton livebirths from 2009 to 2018 at a single institution with a diagnosis of preeclampsia were obtained. Text searching was used to obtain placental data from pathology reports, including lesions of MVM, fetal vascular malperfusion (FVM), chronic inflammation (CI), and acute inflammation (AI). Placental pathology was compared based on timing of delivery and latent class analysis (LCA) was used to investigate subtypes of preeclampsia based on 22 placental variables. RESULTS: 728 patients were included in the analysis. Prevalence of MVM decreased with advancing gestation (95.4% at <34 weeks, 69.8% at 34-36 weeks, and 50%, ≥37 weeks; p < 0.01). LCA identified five classes based on placental pathology: (1) high grade MVM, (2) CI and FVM, (3) low grade MVM, (4) AI, (5) other. Preterm birth varied across the classes (p < 0.01), with the highest prevalence observed among the classes characterized by MVM (high grade: 87.6%; low grade: 63.0%) and the lowest prevalence among the class characterized by AI (23.5%). DISCUSSION: Placental pathology in preeclampsia differs based on gestational age at delivery with MVM seen in nearly all early onset preeclampsia cases. Latent classes largely grouped by previously defined patterns of placental injury (MVM, CI, FVM, AI), and again revealed the highest likelihood of preterm birth in classes characterized by MVM. Results suggest there may be multiple mechanisms leading to the clinical manifestations of preeclampsia.


Assuntos
Pré-Eclâmpsia , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Placenta/patologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/patologia , Resultado da Gravidez/epidemiologia , Gravidez Múltipla , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/patologia
8.
Sci Rep ; 13(1): 10380, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37369688

RESUMO

Exposure to traumatic events during pregnancy may influence pregnancy and birth outcomes. Growing evidence suggests that exposure to traumatic events well before pregnancy, such as childhood maltreatment (CM), also may influence the course of pregnancy and risk of adverse birth outcomes. We aimed to estimate associations between maternal CM exposure and small-for-gestational-age birth (SGA) and preterm birth (PTB) in a diverse US sample, and to examine whether common CM-associated health and behavioral sequelae either moderate or mediate these associations. The Measurement of Maternal Stress (MOMS) Study was a prospective cohort study that enrolled 744 healthy English-speaking participants ≥ 18 years with a singleton pregnancy, who were < 21 weeks at enrollment, between 2013 and 2015. CM was measured via the Childhood Trauma Questionnaire (CTQ) and participants above the moderate/severe cut-off for any of the five childhood abuse and neglect scales were assigned to the CM-exposed group. Common CM-associated health (obesity, depressive symptoms, hypertensive disorders) and behavioral (substance use) sequelae were obtained from standardized questionnaires and medical records. The main outcomes included PTB (gestational age < 37 weeks at birth) and SGA (birthweight < 10%ile for gestational age) abstracted from the medical record. Multivariable logisitic regression was used to test associations between CM, sequeale, and birth outcomes, and both moderation and mediation by CM-related sequelae were tested. Data were available for 657/744 participants. Any CM exposure was reported by 32% of participants. Risk for SGA birth was 61% higher among those in the CM group compared to the non-CM group (14.1% vs. 7.6%), and each subsequent form of CM that an individual was exposed to corresponded with a 27% increased risk for SGA (aOR 1.27, 95% CI 1.05, 1.53). There was no significant association between CM and PTB (9.3% vs. 13.0%, aOR 1.07, 95% CI 0.58, 1.97). Of these sequelae only hypertensive disorders were associated with both CM and SGA and hypertensive disorders of pregnancy did not mediate the association between CM and SGA. Our findings indicate that maternal CM exposure is associated with increased risk for SGA birth and highlight the importance of investigating the mechanisms whereby childhood adversity sets the trajectory for long-term and intergenerational health issues.


Assuntos
Hipertensão Induzida pela Gravidez , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Criança , Lactente , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Exposição Materna , Estudos Prospectivos , Recém-Nascido Pequeno para a Idade Gestacional , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Retardo do Crescimento Fetal
9.
Am J Obstet Gynecol MFM ; 5(8): 101012, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37169285

RESUMO

BACKGROUND: Some data suggest an association between abnormal fetal fraction on noninvasive prenatal screening and adverse pregnancy outcomes, including low birthweight, preeclampsia, and preterm birth in the absence of aneuploidy. These findings suggest that abnormal fetal fraction may be associated with placental pathologic processes in early gestation. OBJECTIVE: This study aimed to determine the independent association of fetal fraction on genetic noninvasive prenatal screening with histologic placental types. STUDY DESIGN: This was a retrospective cohort study at a single institution in the period between January 2017 and March 2021, including live births at ≥24 weeks for which noninvasive prenatal screening was performed and placental pathology results were available. Results were stratified by trimester of noninvasive prenatal screening. Clinical characteristics were compared by quartile of fetal fraction using chi-square tests. Linear regression was used to model continuous fetal fraction as a function of 3 histologic types representing chronic placental injury-chronic inflammation, maternal vascular malperfusion, and fetal vascular malperfusion. Inverse probability weighting was used to account for selection bias in characteristics of patients with placental pathology examination. RESULTS: A total of 1374 patients had noninvasive prenatal screening in the first trimester and 262 in the second trimester. Preterm birth and hypertensive disorders of pregnancy were most common in the lowest quartile of fetal fraction. Chronic inflammation was associated with a 0.56 percentage point reduction in fetal fraction (95% confidence interval, -0.95 to -0.16), and maternal vascular malperfusion was associated with a 0.48 percentage point reduction in fetal fraction (95% confidence interval, -0.91 to -0.04) in adjusted models. The association with maternal vascular malperfusion was no longer statistically significant after accounting for selection bias in placentas sent for pathologic examination. Second-trimester fetal fraction was not associated with placental pathology. CONCLUSION: Chronic inflammation is associated with lower first-trimester fetal fraction even after accounting for selection bias. Higher fetal fraction in the second trimester was associated with fetal vascular pathology, although this association was no longer statistically significant after inverse probability weighting to account for selection bias. First-trimester fetal fraction may be a biomarker of adverse outcomes associated with chronic inflammation.


Assuntos
Placenta , Nascimento Prematuro , Gravidez , Recém-Nascido , Humanos , Feminino , Placenta/patologia , Primeiro Trimestre da Gravidez , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Inflamação/diagnóstico , Inflamação/epidemiologia , Inflamação/patologia
10.
Pediatr Dev Pathol ; 26(4): 388-393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37249143

RESUMO

BACKGROUND: Differences in the shape of the ductus arteriosus (DA), an important vascular shunt between the pulmonary artery and aorta, may reflect fetoplacental blood flow. Our aim was to examine tapering of the DA in a fetal autopsy population and correlate it with placental pathology and cause of death (COD). METHODS: This autopsy case control study of stillborn fetuses selected cases (tapered DA) and consecutive age-matched controls (no DA tapering) between January 2017 and January 2022. We abstracted demographic and clinical data from pathology reports. Autopsy data included COD and histologic evidence of fetal hypoxia. Placental pathology included umbilical cord abnormalities, acute and chronic inflammation, fetal vascular malperfusion (FVM), and maternal vascular malperfusion (MVM). RESULTS: We identified 50 cases and 50 controls. Gestational age ranged from 18 to 38 weeks. Maternal and fetal demographic characteristics did not differ significantly between cases and controls. COD related to an umbilical cord accident/FVM was significantly more prevalent in cases vs controls (46% vs 26%, P = .037), and FVM in the placenta, regardless of COD, trended higher in cases than controls. CONCLUSION: Tapering of the DA is present in stillborn fetuses and associated with COD related to fetal vascular blood flow obstruction.


Assuntos
Canal Arterial , Doenças Placentárias , Doenças Vasculares , Gravidez , Feminino , Humanos , Lactente , Placenta/patologia , Autopsia , Estudos de Casos e Controles , Canal Arterial/patologia , Causas de Morte , Natimorto , Doenças Placentárias/patologia , Doenças Vasculares/patologia
11.
Pediatr Dev Pathol ; 26(3): 310-317, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37082927

RESUMO

BACKGROUND: Placental maternal vascular malperfusion (MVM) is associated with fetal growth restriction (FGR). While FGR increases the risk of cardiovascular disease, the impact of MVM on fetal cardiac structure is understudied. METHODS: We utilized a cohort of autopsied stillbirths; 29 with MVM as the cause of death and 21 with a cause of death unrelated to MVM. Fetal and organ weights and heart measurements were standardized by gestational age and compared between MVM and non-MVM stillbirths. Differences in standardized fetal organ and cardiac measures as compared to standardized fetal body weight were calculated to account for body size. RESULTS: MVM stillbirths had smaller organ and heart weights than non-MVM stillbirths; however, after accounting for gestational age, heart weight was the least affected among all organs. In an analysis of organ weights relative to body size, heart weights were 0.31 standard deviations (SD) larger than expected relative to body weight (95% CI: 0.04, 0.57). Right and left ventricle thicknesses and mitral valve circumference were also larger than expected relative to body weight. CONCLUSION: Stillbirth due to MVM was associated with relative sparing of heart weight and other heart measurements. The significance of these findings in liveborn infants needs further study.


Assuntos
Placenta , Natimorto , Humanos , Gravidez , Feminino , Placenta/patologia , Desenvolvimento Fetal , Retardo do Crescimento Fetal/patologia , Peso Corporal
12.
J Perinatol ; 43(2): 155-161, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36585507

RESUMO

OBJECTIVE: The objective of the paper was to investigate how neonatal hematologic outcomes vary by major placental histopathology categories. STUDY DESIGN: Placental pathology reports from 5263 subjects were coded into individual placental lesions. Infant hematologic data (complete blood count parameters (n = 1945), transfusions, and phototherapy) were compared by placental pathologic phenotype. RESULTS: Red blood cell transfusions were more likely with maternal vascular malperfusion (MVM; OR 9.4 [2.2, 40.8]) and chronic inflammation (1.7 [1.04, 2.7]). White blood cells were decreased with MVM (10.6 103/µL vs 16.4) and elevated with acute inflammation (AI; 18.6 vs 11.9). Thrombocytopenia was associated with MVM (OR 3.7 [2.2, 5.1]) and fetal vascular malperfusion (FVM; OR 2.6 [1.5, 4.6]). Platelet transfusions were more likely with MVM (OR 8.3 [4.6, 15.0]) and FVM (OR 2.9 [1.4, 6.1]). Phototherapy was associated with MVM (OR 3.3 [2.7, 4.0]) and AI (OR 0.8 [0.6, 0.9]). CONCLUSIONS: Neonatal hematologic outcomes are associated with the in utero environment described by placental pathology.


Assuntos
Placenta , Trombocitopenia , Gravidez , Feminino , Humanos , Placenta/patologia , Resultado da Gravidez , Estudos Retrospectivos , Inflamação
14.
Sci Adv ; 8(23): eabn3328, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35675391

RESUMO

In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

15.
Am J Obstet Gynecol ; 227(6): 887.e1-887.e15, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35764136

RESUMO

BACKGROUND: Histologic examination of the placenta is often performed after preterm birth. Although placental examination cannot change the index pregnancy outcome, it may inform the risk of adverse outcomes in a subsequent pregnancy. Previous research has examined the association between individual histologic lesions and pregnancy outcomes without consistent results. OBJECTIVE: This study aimed to determine the independent contributions of the major placental pathology histologic types to recurrent preterm birth. STUDY DESIGN: This was a retrospective cohort study of deliveries at a tertiary care center from January 2009 to March 2018. Individuals with ≥2 births, an index birth of <37 weeks of gestation, and a placental pathology report from the index pregnancy were included. The presence of maternal vascular malperfusion, fetal vascular malperfusion, acute inflammation, and chronic inflammation was extracted from the pathology reports for each index placenta and classified as none, low grade, or high grade. A log-binomial model incorporating all 4 placental pathology histologic types, index gestational age, race, and maternal age was used to estimate the associations between each placental histologic type and risk of recurrent preterm birth. Moreover, 2-way interaction terms were studied among placental histologic types. In addition, 2 stratified analyses were completed on the basis of characteristics of the index preterm birth: (1) by late preterm (gestational age of 34-36 weeks) vs early-to-moderate preterm birth (<34 weeks) and (2) a subgroup analysis of those with spontaneous preterm birth. RESULTS: A total of 924 pregnancy pairs met the inclusion criteria. Only high-grade chronic inflammation was independently associated with an increased risk of recurrent preterm birth (adjusted risk ratio, 1.37; 95% confidence interval, 1.03-1.81). Stratified analysis by gestational age group demonstrated maternal vascular malperfusion was associated with recurrent preterm birth only among those with early preterm birth (adjusted risk ratio, 1.40; 95% confidence interval, 1.01-1.93). Among participants with spontaneous preterm labor, no association was found between pathology histologic types and risk of preterm birth. CONCLUSION: Among index preterm pregnancies, high-grade chronic placental inflammation was associated with recurrent preterm birth. Low-grade maternal vascular malperfusion was associated with recurrent preterm birth only among those with an early or moderate index preterm birth (<34 weeks of gestation). These findings may be useful in determining the risk profile for individual patients and may generate hypotheses as to the pathogenesis of recurrent preterm birth.


Assuntos
Placenta , Nascimento Prematuro , Gravidez , Recém-Nascido , Humanos , Feminino , Lactente , Placenta/irrigação sanguínea , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Resultado da Gravidez , Inflamação/complicações
16.
Sci Adv ; 8(3): eabl5417, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35044830

RESUMO

There are substantial, unexplained racial disparities in women's health. Some of the most pronounced involve elevated rates of preterm delivery (PTD) and cardiovascular disease (CVD) among Black women. We hypothesized that stress associated with excessive use of force by police may contribute to these disparities. In two prospective cohorts derived from electronic health records (pregnancy cohort, N = 67,976; CVD cohort, N = 6773), we linked formal complaints of excessive police force in patients' neighborhoods with health outcomes. Exposed Black women were 1.19 times as likely to experience PTD [95% confidence interval (CI): 1.04 to 1.35] and 1.42 times as likely to develop CVD (95% CI: 1.12 to 1.79), even after adjustment for neighborhood disadvantage and homicide. The excess risks of PTD were also observed in maternal fixed-effects analyses comparing births to the same woman. These findings suggest police violence may be an unrecognized contributor to health inequity for Black women.


Assuntos
Doenças Cardiovasculares , Nascimento Prematuro , População Negra , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Recém-Nascido , Polícia , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Prospectivos , Características de Residência
17.
Am J Reprod Immunol ; 87(3): e13489, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34958140

RESUMO

BACKGROUND: Preterm birth rates are higher among individuals of lower socioeconomic status and non-White race, which is possibly related to life-course stressors. It is important to understand the underlying mechanisms of these health disparities, and inflammation is a possible pathway to explain the disparities in birth outcomes. OBJECTIVE: In this study, we aimed to determine whether patterns of inflammation differed by maternal race and socioeconomic status. STUDY DESIGN: Seven hundred and forty-four participants in a multi-site, prospective study of pregnancy and birth outcomes provided biological and psychological data between 12'0-20'6 weeks gestation. Participants with recent infection, fever, antibiotics or steroid treatment were excluded. Cytokines including INFÉ£, IL-10, IL-13, IL-6, IL-8, and TNFα, and the acute phase protein CRP were measured in serum and values and were log-transformed for normality when appropriate, and a non-orthogonal rotation (Oblimid) was performed to allow the extracted factor to inter-correlate. IFNγ, IL-8, IL-10, IL-6, TNF-a, and IL-13 loaded onto Inflammatory Factor 1 (IF-1), while CRP and IL-6 loaded onto Inflammatory Factor 2 (IF-2). Race and education were collected via self-report during an in-person study visit. Multivariable models were used to determine the association of race and SES with IF-1 and IF-2 during the second trimester, and a mediation model was used to examine if inflammation is on the causal pathway. Models were adjusted for study site, prenatal age, pre-pregnancy BMI, smoking during pregnancy, and gestational age at the time of blood collection. RESULTS: Six hundred and five participants were included in our final analysis, with 61.2% of low or moderate SES, and 35.5% identifying as a person of color (POC). Identifying as a POC, being of low and moderate SES, and being both low-SES and POC or moderate-SES and POC were associated with higher odds of preterm birth and lower birth weight percentile infants. Low SES POC participants had significantly higher IF-1 and IF-2 scores when compared to high-SES White participants. Additionally, higher IF-1 and IF-2 were associated with shorter gestation. In the mediation analysis, we observed a significant direct effect of race/SES on preterm birth; however, the results did not support an indirect pathway where IF-1 or IF-2 acted as mediators. CONCLUSION: Maternal race and SES are significantly associated with inflammatory biomarkers during pregnancy, and when race and SES are considered in combination, they are stronger predictors of adverse pregnancy outcomes than when evaluated separately.


Assuntos
Resultado da Gravidez , Nascimento Prematuro , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/epidemiologia , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Classe Social
18.
J Epidemiol Community Health ; 76(4): 398-403, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607891

RESUMO

BACKGROUND: Housing instability is associated with adverse pregnancy outcomes. Recent studies indicate that eviction, which may affect a larger segment of the population than other forms of housing instability, is also associated with adverse pregnancy outcomes. However, these studies evaluate eviction across large areas, such as counties, so it remains unclear whether these patterns extend to individual-level pregnancy outcomes. METHODS: We used data on a cohort of all singleton live births at a single Chicago hospital between March 2008 and March 2018 to investigate the associations between block-group eviction rates and individual adverse pregnancy outcomes. Eviction data were obtained from the Eviction Lab at Princeton University. Generalised estimating equations were used to estimate associations and account for correlations among individuals living in the same block groups. RESULTS: Individuals living in block groups in the highest quartile for eviction filing rate were 1.17 times as likely to deliver preterm (95% CI: 1.08 to 1.27) and 1.13 times as likely to deliver a small for gestational age infant (95% CI: 1.03 to 1.25) as compared with individuals living in block groups in the lowest quartile. Further, tests for linear trend indicated that for each quartile increase in eviction filing rate, there was a corresponding increase in odds of adverse outcomes (p<0.05). Results were strongest in magnitude for those with low neighbourhood and individual socioeconomic status, who are most likely to be renters and affected by local eviction policies. CONCLUSION: Our results suggest that individuals living in block groups with higher eviction rates are more likely to deliver preterm. Future research should explore associations of individual experience with eviction on adverse pregnancy outcomes and examine whether policies to improve tenant protections also impact pregnancy outcomes.


Assuntos
Nascimento Prematuro , Feminino , Habitação , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Características de Residência
19.
Am J Reprod Immunol ; 86(6): e13497, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34477256

RESUMO

OBJECTIVE: Inflammation as a risk factor for preterm birth is well-established. The primary objective of this analysis was to examine whether individual cytokines versus a composite indicator of mid-pregnancy inflammation are significantly associated with risk for adverse birth outcomes. STUDY DESIGN: A multi-site prospective study was conducted in a socio-demographically diverse cohort of 610 pregnant participants. At a study visit between 12 and 20 6/7 weeks' gestation, low-grade inflammation was measured via log-transformed serum concentrations of the biomarkers IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α, and CRP. Principal component analysis (PCA) was used to identify underlying dimensions of inflammatory activity from the seven biomarkers measured. Gestational age and birth weight at delivery were obtained from medical chart review. The associations between inflammatory profiles and birth outcomes were assessed via linear and logistic regression models. Results were compared with those from individual inflammatory biomarkers, and model fit was assessed using Akaike's Information Criterion (AIC). RESULTS: Principal component analysis analysis yielded a two-factor solution, with the first factor (IF1) composed of IL-8, IL-10, IL-13, IFN-É£, and TNF-α, and the second factor (IF2) containing IL-6 and CRP. When adjusted for race, education, BMI, smoking status, gestational age at time of blood draw, and study site, a one standard deviation (SD) increase in IF1 remained significantly associated with a decrease in standardized gestational age (ß = -.13, 95% CI: -.21, -.05) and an increase in odds of preterm delivery (OR = 1.46, 95% CI: 1.13, 1.88) (Table 3). A one SD increase in IF2 was similarly associated with a decrease in standardized gestational age at delivery (ß = -.13, 95% CI: -.23, -.04) and an increase in odds of preterm delivery (OR: 1.46, 95% CI: 1.04, 2.05). Neither IF1 nor IF2 was associated with measures of fetal growth. AIC identified that IL-6 was a slightly better fit for length of gestation compared to either composite measure, though all performed similarly. CONCLUSION: Independent of known sociodemographic risk factors, an elevated mid-pregnancy inflammatory profile was associated with a nearly 50% increase in odds of preterm delivery. The composite performed similarly to IL-6. These results suggest that maternal low-grade inflammation is a risk factor for preterm delivery, and that mid-pregnancy inflammatory biomarkers may be useful in predicting risk for preterm delivery.


Assuntos
Citocinas/sangue , Inflamação/sangue , Complicações na Gravidez/sangue , Adulto , Biomarcadores/sangue , Peso ao Nascer/fisiologia , Feminino , Idade Gestacional , Humanos , Gravidez , Resultado da Gravidez , Análise de Componente Principal , Estudos Prospectivos , Adulto Jovem
20.
Placenta ; 112: 135-140, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34352489

RESUMO

INTRODUCTION: Chronic villitis is an inflammatory lesion that affects 5-15% of placentas and is associated with adverse pregnancy outcomes. Chronic villitis may also recur; however, studies estimating recurrence are based on small samples and estimates of recurrence range from 10 to 56%. METHODS: We utilized data from placentas submitted to pathology at a Chicago hospital between January 2009 and March 2018. During the study period, 883 patients had two placentas submitted to pathology. We estimated the risk of recurrent chronic villitis, adjusted for maternal and pregnancy characteristics. We also evaluated whether prevalence of small for gestational age infant differed for those with recurrent chronic villitis and we investigated whether placental pathology worsened in the second study pregnancy among those with recurrent chronic villitis. RESULTS: The overall prevalence of recurrent chronic villitis in the study sample was 11.5%. Among those with chronic villitis in the first pregnancy, 54% developed chronic villitis in the second pregnancy, corresponding to an adjusted risk ratio of 2.36 (95% confidence interval: 1.92, 2.91). Recurrent chronic villitis was not associated with increased prevalence of small for gestational infant as compared with non-recurrent villitis. Among those with recurrent chronic villitis, high-grade chronic inflammation and fetal vascular malperfusion were more common in the second pregnancy as compared with the first. DISCUSSION: Our results suggest that those with chronic villitis in the first pregnancy are over twice as likely to develop chronic villitis in the second pregnancy and that chronic inflammation and fetal vascular malperfusion may worsen among those with recurrent chronic villitis.


Assuntos
Corioamnionite/patologia , Vilosidades Coriônicas/patologia , Adulto , Doença Crônica , Feminino , Humanos , Razão de Chances , Gravidez , Recidiva
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