Placental mitochondrial DNA mutational load and perinatal outcomes: Findings from a multi-ethnic pregnancy cohort.
Ontology highlight
ABSTRACT:
SUBMITTER: Cowell W
PROVIDER: S-EPMC8299859 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Placental mitochondrial DNA mutational load and perinatal outcomes: Findings from a multi-ethnic pregnancy cohort.
Cowell Whitney W Brunst Kelly K Colicino Elena E Zhang Li L Zhang Xiang X Bloomquist Tessa R TR Baccarelli Andrea A AA Wright Rosalind J RJ
Mitochondrion 20210606
Mitochondria fuel placental activity, with mitochondrial dysfunction implicated in several perinatal complications. We investigated placental mtDNA mutational load using NextGen sequencing in relation to birthweight and gestational length among 358 mother-newborn pairs. We found that higher heteroplasmy, especially in the hypervariable displacement loop region, was associated with shorter gestational length. Results were similar among male and female pregnancies, but stronger in magnitude among ...[more]
Similar Datasets
Project description:IntroductionPlacental alterations caused by severe acute respiratory coronavirus-2 (SARS-CoV-2) infection have already been described, but most studies used small sample groups and the difference according to the severity of the disease has not been verified. Our objective was to describe placental alterations in patients with coronavirus disease 2019 (COVID-19) and analyze the association of pathological placental findings with the clinical parameters of COVID-19 and perinatal results.MethodsThis was a nested study within a prospective cohort study involving 109 symptomatic pregnant women with COVID-19. The prevalence of observed placental alterations was described, and the associations of pathological findings with the clinical parameters of COVID-19 severity and with perinatal outcomes were assessed.ResultsThe frequency of types of placental features was poor maternal vascular perfusion in 45% of cases, poor fetal vascular perfusion in 33.9%, hematogenous origin infection in 32.1%, and morphological changes corresponding to ascending infection in 21.1%. Hematogenous infection differed significantly according to COVID-19 severity (p = 0.008), with a prevalence ratio (PR) of 1.74 (95% confidence interval, 1.02-2.98) in the moderate COVID-19 group compared to the mild COVID-19 group. Among the perinatal outcomes, there was an unexpected inverse association between prematurity and placental infection of hematogenous origin, with lower rates of prematurity among cases with inflammation of hematogenous origin (p = 0.029).DiscussionModerate SARS-Cov-2 infection presented a higher prevalence of placental pathological findings. There was no association of placental findings with adverse perinatal outcomes.
| S-EPMC9420243 | biostudies-literature
Project description:(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.
| S-EPMC8473449 | biostudies-literature
Project description:The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnancy outcomes. A retrospective cohort study on 47 pregnant women with confirmed SARS-CoV-2 infection, matched with non-infected controls, was conducted. Relevant clinicopathological data and primary birth outcomes were recorded. Histomorphology and SARS-CoV-2 immunohistochemistry analyses of placental tissues were performed. Only 1 of 47 cases showed SARS-CoV-2 immunoreactivity in the syncytiotrophoblasts. Histologically, decidual vasculopathy (n = 22/47, p = 0.004), maternal vascular thrombosis (n = 9/47, p = 0.015) and chronic histiocytic intervillositis (n = 10/47, p = 0.027) were significantly higher in the COVID-19-infected placentas when compared to the control group. Maternal vascular thrombosis was a significant feature in the active COVID-19 group. A significant lower gestational age (p < 0.001)) at delivery and a higher caesarean section rate (p = 0.007) were observed in the active SARS-CoV-2-infected cases, resulting in a significant lower fetal-placental weight ratio (p = 0.022) and poorer Apgar score (p < 0.001). Notably, active (p = 0.027), symptomatic (p = 0.039), severe-critical (p = 0.002) maternal COVID-19 infection and placental inflammation (p = 0.011) were associated with an increased risk of preterm delivery. Altered placental villous maturation and severe-critical maternal COVID-19 infection were associated with an elevated risk of poor Apgar scores at birth (p = 0.018) and maternal mortality (p = 0.023), respectively.
| S-EPMC9368100 | biostudies-literature
Project description:Sequestration of Plasmodium parasites in the placental vasculature causes increased morbidity and mortality in pregnant compared to non-pregnant patients in malaria-endemic regions. In this study, outbred pregnant CD1 mice with semi allogeneic fetuses were infected with transgenic Plasmodium berghei or mock-inoculated by mosquito bite at either embryonic day (E) 6 (first trimester-equivalent) or 10 (second trimester-equivalent) and compared with non-pregnant females. P. berghei-infected mosquitoes had greater biting avidity for E10 dams than uninfected mosquitoes, which was not apparent for E6 dams nor non-pregnant females. Infected E10 dams had greater numbers of parasites than E6 dams in the uterus and spleen, but not in the blood or liver. While parasites were found in placentas, no parasites were present in fetuses. Maternal infection at E6 caused greater maternal morbidity, with greater rates of fetal reabsorption and stillbirths than at E10. Infection at E10 caused adverse offspring outcomes, including growth restriction. To identify possible mechanisms of adverse offspring outcomes, E10 dams were euthanized during peak parasitemia (8 days post infection), and outcomes were compared with mock-infected dams. P. berghei caused significant systemic maternal immune activation with elevated circulating lymphocytes, eosinophils, and neutrophils and splenic cytokine concentrations. P. berghei infection at E10 increased corticosterone and decreased progesterone concentrations, which could contribute to adverse perinatal outcomes through immunomodulation. There were limited changes in the maternal fecal microbiome after P. berghei infection. Mosquito bite infection of outbred dams with P. berghei causes placental malaria and provides a novel, tractable model to investigate therapeutic treatments.
| S-EPMC11761038 | biostudies-literature
Project description:BackgroundRacial disparities in preterm birth and infant death have been well documented. Less is known about racial disparities in neonatal morbidities among infants who are born at <37 weeks of gestation.ObjectiveThe purpose of this study was to determine whether the risk for morbidity and death among infants who are born preterm differs by maternal race.Study designA retrospective cohort design included medical records from preterm deliveries of 19,325 black, Hispanic, and white women in the Consortium on Safe Labor. Sequentially adjusted Poisson models with generalized estimating equations estimated racial differences in the risk for neonatal morbidities and death, controlling for maternal demographics, health behaviors, and medical history. Sex differences between and within race were examined.ResultsBlack preterm infants had an elevated risk for perinatal death, but there was no difference in risk for neonatal death across racial groups. Relative to white infants, black infants were significantly more likely to experience sepsis (9.1% vs 13.6%), peri- or intraventricular hemorrhage (2.6% vs 3.3%), intracranial hemorrhage (0.6% vs 1.8%), and retinopathy of prematurity (1.0% vs 2.6%). Hispanic and white preterm neonates had similar risk profiles. In general, female infants had lower risk relative to male infants, with white female infants having the lowest prevalence of a composite indicator of perinatal death or any morbidity across all races (30.9%). Differences in maternal demographics, health behaviors, and medical history did little to influence these associations, which were robust to sensitivity analyses of pregnancy complications as potential underlying mechanisms.ConclusionPreterm infants were at similar risk for neonatal death, regardless of race; however, there were notable racial disparities and sex differences in rare, but serious, adverse neonatal morbidities.
| S-EPMC5572800 | biostudies-literature
Project description:ObjectiveTo assess the association between allostatic load, as an estimate of chronic stress, and adverse pregnancy outcomes.MethodsThis was a secondary analysis of nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort study. Our primary exposure was dichotomous high allostatic load in the first trimester, defined as 4 or more of 12 biomarkers in the "worst" quartile. The primary outcome was a composite adverse pregnancy outcome: hypertensive disorders of pregnancy (HDP), preterm birth, small for gestational age (SGA), and stillbirth. Secondary outcomes included components of the composite. Multivariable logistic regression was used to test the association between high allostatic load and adverse pregnancy outcomes, adjusted for potential confounders. Mediation and moderation analyses were conducted to assess the role of allostatic load along the causal pathway between racial disparities and adverse pregnancy outcomes.ResultsAmong 4,266 individuals, 34.7% had a high allostatic load. Composite adverse pregnancy outcome occurred in 1,171 (27.5%): 14.0% HDP, 8.6% preterm birth (48.0% spontaneous and 52.2% indicated), 11.0% SGA, and 0.3% stillbirth. After adjustment for maternal age, gravidity, smoking, bleeding in the first trimester, and health insurance, high allostatic load was significantly associated with a composite adverse pregnancy outcome (adjusted odds ratio [aOR] 1.5, 95% CI 1.3, 1.7) and HDP (aOR 2.5, 95% CI 2.0-2.9), but not preterm birth or SGA. High allostatic load partially mediated the association between self-reported race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race, but not for a composite adverse pregnancy outcome, preterm birth, or SGA.ConclusionHigh allostatic load in the first trimester is associated with adverse pregnancy outcomes, particularly HDP. Allostatic load was a partial mediator between race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race.
| S-EPMC9712159 | biostudies-literature
Project description:ObjectiveTo evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders.Study designA prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was "adverse neonatal outcome", including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxic-ischemic encephalopathy, intracranial hemorrhage or respiratory distress.ResultsOut of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2-3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1-4.3).ConclusionWhen previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor.
| S-EPMC4881909 | biostudies-literature
Project description:ImportanceStatins are the drug class most commonly used to treat hyperlipidemia. Recently, they have been used during pregnancy for the prevention or treatment of preeclampsia. However, the safety of statin use during pregnancy has been questioned, and the sample sizes of most previous studies have been small.ObjectiveTo examine the perinatal outcomes among offspring associated with maternal use of statins during pregnancy.Design, setting, and participantsThis retrospective cohort study included 1 443 657 pregnant women 18 years of age or older with their first infant born during the period from January 1, 2004, to December 31, 2014. Data for this study were taken from the Taiwan National Health Insurance Research Database. Statistical analysis was performed from April 7, 2020, to July 31, 2021.ExposuresMaternal statin use during pregnancy.Main outcomes and measuresWomen who have received a diagnosis of hyperlipidemia before pregnancy and who were receiving prescription statins during pregnancy were the statin-exposed group. Data on congenital anomalies, birth weight, gestational age, preterm birth, low birth weight, very low birth weight, fetal distress, and Apgar score were compared between participants with and partcipants without statin exposure during pregnancy. Risk ratios (RRs) were calculated by multivariable analyses using Poisson regression models to adjust for potential confounders. Subgroup analysis was performed to compare offspring of women who used statins for more than 3 months prior to pregnancy and maintained or stopped statin use after pregnancy.ResultsA total of 469 women (mean [SD] age, 32.6 [5.4] years; mean [SD] gestational age, 38.4 [1.6] weeks) who used statins during pregnancy and 4690 age-matched controls (mean [SD] age, 32.0 [4.9] years; mean [SD] gestational age, 37.3 [2.4] weeks) with no statin exposure during pregnancy were enrolled. After controlling for maternal comorbidities and age, low birth weight was more common among offspring in the statin-exposed group (RR, 1.51 [95% CI, 1.05-2.16]), with a greater chance of preterm birth (RR, 1.99 [95% CI, 1.46-2.71]), and a lower 1-minute Apgar score (RR, 1.83 [95% CI, 1.04-3.20]). Congenital anomalies were not associated with statin exposure during pregnancy. In addition, multivariable analysis showed that there was no association between statin use for periconceptual hyperlipidemia and adverse perinatal outcomes among women who had used statins prior to pregnancy.Conclusions and relevanceThis study suggests that statins may be safe when used during pregnancy because there was no association with congenital anomalies, but caution is needed because of an increased risk of low birth weight and preterm labor. The data also suggest that statins could be safely used during pregnancy for women with long-term use of statins before pregnancy.
| S-EPMC8719244 | biostudies-literature
Project description: Not available
| S-EPMC10694398 | biostudies-literature
Project description:ObjectiveThis study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term.Study designWe performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008-2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic-ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by ≥ 3 days), brachial plexus palsy, or facial nerve palsy.ResultsOf the 72,117 patients included, 48% were White, 20% Black, 5% Asian, and 26% Hispanic. The unadjusted risk of the primary outcome was highest for neonates of Black patients (3.1%, unadjusted relative risk [uRR] = 1.16, 95% confidence interval [CI]: 1.04-1.30), lowest for neonates of Hispanic patients (2.1%, uRR = 0.80, 95% CI: 0.71-0.89), and no different for neonates of Asian (2.6%), compared with those of White patients (2.7%). In the adjusted model including age, body mass index (BMI), smoking, obstetric history, and high-risk pregnancy, differences in risk for the primary outcome were no longer observed for neonates of Black (adjusted relative risk [aRR] = 1.06, 95% CI: 0.94-1.19) and Hispanic (aRR = 0.92, 95% CI: 0.81-1.04) patients. Adding insurance to the model lowered the risk for both groups (aRR = 0.85, 95% CI: 0.75-0.96 for Black; aRR = 0.68, 95% CI: 0.59-0.78 for Hispanic).ConclusionAlthough neonates of Black patients have the highest frequency of adverse perinatal outcomes at term, after adjustment for sociodemographic factors, this higher risk is no longer observed, suggesting the importance of developing strategies that address social determinants of health to lessen extant health disparities.Key points· Term neonates of Black patients have the highest crude frequency of adverse perinatal outcomes.. · After adjustment for confounders, higher risk for neonates of Black patients is no longer observed.. · Disparities in outcomes are strongly related to insurance status..
| S-EPMC8630098 | biostudies-literature