Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes.
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ABSTRACT:
SUBMITTER: Doyle RM
PROVIDER: S-EPMC5507499 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
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Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes.
Doyle Ronan M RM Harris Kathryn K Kamiza Steve S Harjunmaa Ulla U Ashorn Ulla U Nkhoma Minyanga M Dewey Kathryn G KG Maleta Kenneth K Ashorn Per P Klein Nigel N
PloS one 20170712 7
Preterm birth is a major cause of neonatal mortality and morbidity worldwide. Bacterial infection and the subsequent inflammatory response are recognised as an important cause of preterm birth. It is hypothesised that these organisms ascend the cervical canal, colonise placental tissues, cause chorioamnionitis and in severe cases infect amniotic fluid and the foetus. However, the presence of bacteria within the intrauterine cavity does not always precede chorioamnionitis or preterm birth. Wherea ...[more]
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Project description:BackgroundPreterm birth (PTB) is a leading cause of neonatal mortality and longer-term morbidity. Acute chorioamnionitis (ACA) is a common cause of PTB, however, there are limited data on the prevalence of ACA and its association with PTB in resource limited settings.MethodsData and samples came from a clinical trial evaluating novel strategies for the prevention of malaria in HIV infected pregnant women in Uganda. Women were enrolled between 12-28 weeks of gestation and followed through delivery. For each placenta delivered, three placental tissue types (membrane roll, umbilical cord and chorionic plate/villous parenchyma) were collected. Slides were assessed for diagnosis of maternal and fetal ACA by microscopic evaluation of neutrophilic infiltration using a standardized grading scale. The primary outcomes were PTB (<37 weeks), low birth weight (LBW, <2500 grams), and small-for-gestational age (SGA, birth weight <10th percentile for age). Univariate and multivariate logistic regression were used to estimate associations between 1) maternal characteristics (age, education, wealth, gravidity, gestational age at enrollment, placental malaria, anti-malarial prophylaxis treatment regimen, HIV disease parameters) and ACA, and 2) associations between ACA and adverse birth outcomes.FindingsA total of 193 placentas were included in the analysis. The prevalence of maternal and fetal ACA was 44.5% and 28.0%, respectively. HIV infected women between 28-43 years of age had a higher risk of maternal ACA compared to those between 17-21 years of age (50.9% vs. 19.1%; aOR = 4.00 (1.10-14.5), p = 0.04) and the diagnosis of severe maternal ACA was associated with a significantly higher risk of PTB (28.6% vs. 6.0%; aOR = 6.04 (1.87-19.5), p = 0.003), LBW (33.3% vs. 9.4%; aOR = 4.86 (1.65-14.3); p = 0.004), and SGA (28.6% vs. 10.1%; aOR = 3.70 (1.20-11.4), p = 0.02). No maternal characteristics were significantly associated with fetal ACA and the diagnosis of fetal ACA was not associated with adverse birth outcomes.ConclusionsHistological evidence of severe maternal ACA was associated with an increased risk of PTB, LBW, and SGA in HIV infected, pregnant Ugandan women.
| S-EPMC6459589 | biostudies-literature
Project description:Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants commonly detected in human serum. Previous studies have observed associations between maternal serum PFAS and adverse pregnancy and birth outcomes such as lower birth weight or pre-eclampsia; however, few studies have explored these associations with birth outcomes and placental tissue PFAS concentration. The placenta is a vital contributor to a healthy pregnancy and may be involved in the mechanism of PFAS reproductive toxicity. Our goal was to measure placental PFAS concentrations and examine associations with birth outcomes (e.g., birth weight, gestational duration). Placenta samples (n = 120) were collected during delivery from women enrolled in the Healthy Pregnancy, Healthy Baby cohort (HPHB) in Durham, North Carolina. All placenta samples contained detectable PFAS, with perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) being the most abundant and most frequently detected (all >96% detection frequency). While placental PFAS concentrations did not differ by infant sex, higher PFAS levels were observed in placenta from nulliparous women, suggesting that parity influences the accumulation of PFAS in the placenta. We used linear regression models to examine associations between placental PFAS and birth outcomes. After adjustment for parity, tobacco use, maternal age, and maternal race, we found that placental PFOS was associated with lower birth weight for gestational age in male infants and higher birth weight for gestational age in female infants. Similar findings were seen for PFNA for birth weight for gestational age. These differences in birth outcomes based on infant sex highlight a need to explore mechanistic differences in PFAS toxicity during gestation for male and female infants.
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Project description:BACKGROUND:Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes. METHODS:This is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIV-uninfected pregnant women were enrolled at 12-20 weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants. RESULTS:The 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0-1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (? 2 episodes of symptomatic malaria or ? 50% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80-111.6) and 4.06 (1.73-9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRR = 3.27 (1.32-8.12) and aRR = 7.07 (2.84-17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46-21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy. CONCLUSION:Higher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes. Trial Registration Current Controlled Trials Identifier NCT02163447.
| S-EPMC5629777 | biostudies-literature
Project description:Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis.In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/or funisitis using state-of-the-science whole-genome shotgun metagenomics.This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9-15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R.Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P = .005), there was no observable impact with either betamethasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects).Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative metagenomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis.
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Project description:BackgroundMalaria during pregnancy is a major contributor to the global burden of adverse birth outcomes including fetal growth restriction, preterm birth, and fetal loss. Recent evidence supports a role for angiogenic dysregulation and perturbations to placental vascular development in the pathobiology of malaria in pregnancy. The Angiopoietin-Tie2 axis is critical for placental vascularization and remodeling. We hypothesized that disruption of this pathway would contribute to malaria-induced adverse birth outcomes.MethodsUsing samples from a previously conducted prospective cohort study of pregnant women in Malawi, we measured circulating levels of angiopoietin-1 (Angpt-1) and Angpt-2 by Luminex (n=1392). We used a preclinical model of malaria in pregnancy (Plasmodium berghei ANKA [PbA] in pregnant BALB/c mice), genetic disruption of Angpt-1 (Angpt1+/- mice), and micro-CT analysis of placental vasculature to test the hypothesis that disruptions to the Angpt-Tie2 axis by malaria during pregnancy would result in aberrant placental vasculature and adverse birth outcomes.FindingsDecreased circulating levels of Angpt-1 and an increased ratio of Angpt-2/Angpt-1 across pregnancy were associated with malaria in pregnancy. In the preclinical model, PbA infection recapitulated disruptions to the Angiopoietin-Tie2 axis resulting in reduced fetal growth and viability. Malaria decreased placental Angpt-1 and Tie2 expression and acted synergistically with reduced Angpt-1 in heterozygous dams (Angpt1+/-), to worsen birth outcomes by impeding vascular remodeling required for placental function.InterpretationCollectively, these data support a mechanistic role for the Angpt-Tie2 axis in malaria in pregnancy, including a potential protective role for Angpt-1 in mitigating infection-associated adverse birth outcomes.FundingThis work was supported by the Canadian Institutes of Health Research (CIHR), Canada Research Chair, and Toronto General Research Institute Postdoctoral Fellowship Award. The parent trial was supported by the European & Developing Countries Clinical Trials Partnership and the Malaria in Pregnancy Consortium, which was funded by the Bill & Melinda Gates Foundation. The funders had no role in design, analysis, or reporting of these studies.
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Project description:ObjectiveTo assess the accuracy of the World Health Organization (WHO) partograph alert line and other candidate predictors in the identification of women at risk of developing severe adverse birth outcomes.DesignA facility-based, multicentre, prospective cohort study.SettingThirteen maternity hospitals located in Nigeria and Uganda.PopulationA total of 9995 women with spontaneous onset of labour presenting at cervical dilatation of ≤6 cm or undergoing induction of labour.MethodsResearch assistants collected data on sociodemographic, anthropometric, obstetric, and medical characteristics of study participants at hospital admission, multiple assessments during labour, and interventions during labour and childbirth. The alert line and action line, intrapartum monitoring parameters, and customised labour curves were assessed using sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and the J statistic.OutcomesSevere adverse birth outcomes.ResultsThe rate of severe adverse birth outcomes was 2.2% (223 women with severe adverse birth outcomes), the rate of augmentation of labour was 35.1% (3506 women), and the caesarean section rate was 13.2% (1323 women). Forty-nine percent of women in labour crossed the alert line (4163/8489). All reference labour curves had a diagnostic odds ratio ranging from 1.29 to 1.60. The J statistic was less than 10% for all reference curves.ConclusionsOur findings suggest that labour is an extremely variable phenomenon, and the assessment of cervical dilatation over time is a poor predictor of severe adverse birth outcomes. The validity of a partograph alert line based on the 'one-centimetre per hour' rule should be re-evaluated.FundingBill & Melinda Gates Foundation, United States Agency for International Development (USAID), UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), and WHO (A65879).Tweetable abstractThe alert line in check: results from a WHO study.
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Project description:Periodontal disease may increase the risk of adverse birth outcomes; however, results have been mixed. Few studies have examined periodontal disease in developing countries. We describe the relationship between periodontal disease and birth outcomes in a community setting in Pakistan.This was a prospective cohort study. Enrollment occurred at 20-26 weeks of gestation. A study dentist performed the periodontal examination to assess probing depth, clinical attachment level, gingival index, and plaque index. Outcomes included stillbirth, neonatal death, perinatal death, < 32 weeks preterm birth, 32-36 weeks preterm birth, and low birthweight and are presented for increasing periodontal disease severity by quartiles.Dental examinations and outcome data were completed for 1152 women: 81% of the women were multiparous, with a mean age of 27 years; 33% of the women had no education. Forty-seven percent of the women had dental caries; 27% of the women had missing teeth, and 91% of the women had had no dental care in the last year. Periodontal disease was common: 76% of the women had > or = 3 teeth with a probing depth of > or = 3 mm; 87% of the women had > or = 4 teeth with a clinical attachment level of > or = 3 mm; 56% of the women had > or = 4 teeth with a plaque index of 3; and 60% of the women had > or = 4 teeth with a gingival index of 3. As the measures of periodontal disease increased from the 1st to 4th quartile, stillbirth and neonatal and perinatal death also increased, with relative risks of approximately 1.3. Early preterm birth increased, but the results were not significant. Late preterm birth and low birthweight were not related to measures of periodontal disease.Pregnant Pakistani women have high levels of moderate-to-severe dental disease. Stillbirth and neonatal and perinatal deaths increased with the severity of periodontal disease.
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Project description:One in five pregnant women suffer from gestational complications, prevalently driven by placental malfunction. Using RNASeq, we analyzed differential placental gene expression in cases of normal gestation, late-onset preeclampsia (LO-PE), gestational diabetes (GD) and pregnancies ending with the birth of small-for-gestational-age (SGA) or large-for-gestational-age (LGA) newborns (n = 8/group). In all groups, the highest expression was detected for small noncoding RNAs and genes specifically implicated in placental function and hormonal regulation. The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes. Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results. A limited number of transcription factors including LRF, SP1 and AP2 were identified as possible drivers of these changes. Notable differences were detected in differential expression signatures of LO-PE subtypes defined by the presence or absence of intrauterine growth restriction (IUGR). LO-PE with IUGR showed higher correlation with SGA and LO-PE without IUGR with LGA placentas. Whereas changes in placental transcriptome in SGA, LGA and GD cases were less prominent, the overall profiles of expressional disturbances overlapped among pregnancy complications providing support to shared placental responses. The dataset represent a rich catalogue for potential biomarkers and therapeutic targets.
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Project description:ImportanceMany studies have reported an association of interpregnancy interval (IPI) between 2 consecutive births with adverse birth outcomes in low- and middle-income countries. However, most of these studies ignore the implications of some unmeasured confounders.ObjectiveTo explore the association of IPI with adverse perinatal outcomes.Design, setting, and participantsThis large-scale cohort study used the Guangdong Provincial Women and Children Health Information System in Guangdong Province, China, to obtain birth data recorded between January 1, 2014, and December 31, 2020. Matched-sibling design was used. The final cohort included first-born and second-born sibling pairs delivered by mothers who were permanent residents of Guangdong Province.ExposuresThe exposure variable was IPI, which was categorized as follows: less than 6, 6 to 11, 12 to 17, 18 to 23, 24 to 29, 30 to 35, and 36 or more months.Main outcomes and measuresThe outcome variables were adverse birth outcomes: preterm birth (PTB, gestational age <37 weeks), low birth weight (LBW, <2500 g), and small for gestational age (SGA). Adjusted odds ratio (OR) and interaction odds ratio (IOR) associated with IPI were calculated.ResultsThe study consisted of 725 392 sibling pairs of multiparous mothers. Among these mothers, 718 111 (99.0%) were aged 20 to 34 years, and 715 583 (98.7%) were of Han Chinese ethnicity. Unmatched analysis showed that a short IPI of less than 6 months was associated with higher risks of PTB (adjusted OR, 1.96; 95% CI, 1.87-2.06), LBW (adjusted OR, 1.88; 95% CI, 1.79-1.98), and SGA (adjusted OR, 1.34; 95% CI, 1.30-1.38) compared with an IPI of 18 to 23 months. These associations were attenuated in the matched-sibling analysis. An association of short IPI (<6 months) with PTB (adjusted IOR, 1.40; 95% CI, 1.30-1.51), LBW (adjusted IOR, 1.30; 95% CI, 1.21-1.40), and SGA (adjusted IOR, 1.16; 95% CI, 1.11-1.22) remained in the matched analysis. For IPI of 36 months or more, the odds of PTB (adjusted OR, 1.08; 95% CI, 1.03-1.14) and LBW (adjusted OR, 1.13; 95% CI, 1.07-1.19) in the unmatched analysis were also greater than the reference interval (18-23 months), but not for SGA (adjusted OR, 0.96; 95% CI, 0.93-0.99). Associations between a long IPI (≥36 months) and PTB (adjusted IOR, 1.10; 95% CI, 1.02-1.19) and LBW (adjusted IOR, 1.16; 95% CI, 1.07-1.26) remained through the sibling comparisons.Conclusions and relevanceResults of this study indicated that mothers with a short (<6 months) or long (≥36 months) IPI had greater odds of adverse birth outcomes. The findings may inform family planning policies and guide individuals and families who are planning for another pregnancy in China.
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