Histological chorioamnionitis is increased at extremes of gestation in stillbirth: a population-based study.
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ABSTRACT: Objective
To determine the incidence of histological chorioamnionitis and a fetal response in stillbirths in New South Wales (NSW), and to examine any relationship of fetal response to spontaneous onset of labour and to unexplained antepartum death.Study design
Population-based cohort study. Setting. New South Wales Australia. Population. All births between 2002 and 2004 with stillbirths reviewed and classified by the state perinatal mortality review committee.Methods
Record linkage of the Midwives Data Collection and the Perinatal Death Database including placental histopathology and standardised cause of death classification.Results
952 stillbirths were included. The incidence of histopathological chorioamnionitis was 22.6%, with a bimodal distribution. A fetal inflammatory response was present in 10.1% and significantly correlated with spontaneous onset of labour. The absence of a fetal inflammatory response was strongly associated with unexplained antepartum death.Conclusions
The increased incidence of histological chorioamnionitis at extremes of gestation is confirmed in the largest dataset to date using population data. This has important implications for late gestation stillbirth as the percentage of unexplained stillbirths increases near term.
SUBMITTER: Gordon A
PROVIDER: S-EPMC3140189 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
Publications
Histological chorioamnionitis is increased at extremes of gestation in stillbirth: a population-based study.
Gordon Adrienne A Lahra Monica M Raynes-Greenow Camille C Jeffery Heather H
Infectious diseases in obstetrics and gynecology 20110719
<h4>Objective</h4>To determine the incidence of histological chorioamnionitis and a fetal response in stillbirths in New South Wales (NSW), and to examine any relationship of fetal response to spontaneous onset of labour and to unexplained antepartum death.<h4>Study design</h4>Population-based cohort study. Setting. New South Wales Australia. Population. All births between 2002 and 2004 with stillbirths reviewed and classified by the state perinatal mortality review committee.<h4>Methods</h4>Rec ...[more]
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Project description:ObjectiveTo assess the main risk factors associated with stillbirth in a multiethnic English maternity population.DesignCohort study.SettingNational Health Service region in England.Population92,218 normally formed singletons including 389 stillbirths from 24 weeks of gestation, delivered during 2009-11.Main outcome measureRisk of stillbirth.ResultsMultivariable analysis identified a significant risk of stillbirth for parity (para 0 and para ≥ 3), ethnicity (African, African-Caribbean, Indian, and Pakistani), maternal obesity (body mass index ≥ 30), smoking, pre-existing diabetes, and history of mental health problems, antepartum haemorrhage, and fetal growth restriction (birth weight below 10th customised birthweight centile). As potentially modifiable risk factors, maternal obesity, smoking in pregnancy, and fetal growth restriction together accounted for 56.1% of the stillbirths. Presence of fetal growth restriction constituted the highest risk, and this applied to pregnancies where mothers did not smoke (adjusted relative risk 7.8, 95% confidence interval 6.6 to 10.9), did smoke (5.7, 3.6 to 10.9), and were exposed to passive smoke only (10.0, 6.6 to 15.8). Fetal growth restriction also had the largest population attributable risk for stillbirth and was fivefold greater if it was not detected antenatally than when it was (32.0% v 6.2%). In total, 195 of the 389 stillbirths in this cohort had fetal growth restriction, but in 160 (82%) it had not been detected antenatally. Antenatal recognition of fetal growth restriction resulted in delivery 10 days earlier than when it was not detected: median 270 (interquartile range 261-279) days v 280 (interquartile range 273-287) days. The overall stillbirth rate (per 1000 births) was 4.2, but only 2.4 in pregnancies without fetal growth restriction, increasing to 9.7 with antenatally detected fetal growth restriction and 19.8 when it was not detected.ConclusionMost normally formed singleton stillbirths are potentially avoidable. The single largest risk factor is unrecognised fetal growth restriction, and preventive strategies need to focus on improving antenatal detection.
| S-EPMC3554866 | biostudies-literature
Project description:BackgroundHistologic chorioamnionitis (HCA) is commonly associated with preterm birth and deleterious post-natal outcomes including sepsis and necrotizing enterocolitis. Transcriptomic analysis has been used to uncover gene signatures that permit diagnosis and prognostication, show new therapeutic targets, and reveal mechanisms that underlie differential outcomes with other complex disease states in neonates such as sepsis.AimsTo define the transcriptomic and inflammatory protein response in peripheral blood among infants with exposure to histologic chorioamnionitis.Study designProspective, observational study.SubjectsUninfected preterm neonates retrospectively categorized based on placental pathology with no HCA exposure (n=18) or HCA exposure (n=15).Outcomes measuresWe measured the transcriptomic and inflammatory mediator response in prospectively collected whole blood.ResultsWe found 488 significant (p<0.001), differentially expressed genes in whole blood samples among uninfected neonates with HCA exposure that collectively represented activated innate and adaptive immune cellular pathways and revealed a potential regulatory role for the pleotropic microRNA molecule miR-155. Differentially secreted plasma cytokines in patients with HCA exposure compared to patients without HCA included MCP-1, MPO, and MMP-9 (p<0.05).ConclusionsExposure to HCA distinctively activates the neonatal immune system in utero with potentially long-term health consequences.
| S-EPMC4947555 | biostudies-literature
Project description:To study the association between total and early pregnancy (<22 completed weeks) weight gain and risk of stillbirth, stratified by early-pregnancy body mass index (BMI).Population-based cohort study.Stockholm-Gotland Region, Sweden.Pregnant women with singleton births (n = 160 560).Pregnancy weight gain was standardised into gestational age-specific z-scores. For analyses of total pregnancy weight gain, a matched design with an incidence density sampling approach was used. Findings were also contrasted with current Institute of Medicine (IOM) weight gain recommendations.Stillbirth defined as fetal death at ?22 completed weeks of gestation.For all BMI categories, there was no statistical association between total or early pregnancy weight gain and stillbirth within the range of a weight gain z-score of -2.0 SD to +2.0 SD. Among normal-weight women, the adjusted odds ratio of stillbirth for lower (-2.0 to -1.0 SD) and higher (+1.0 to +1.9 SD) total weight gain was 0.85 (95% CI; 0.48-1.49) and 1.03 (0.60-1.77), respectively, as compared with the reference category. Further, there were no associations between total or early pregnancy weight gain and stillbirth within the range of weight gain currently recommended by the IOM. For the majority of the BMI categories, the point estimates at the extremes of weight gain values (<-2.0SD and ?2.0 SD) suggested protective effects of low weight gain and increased risks of high weight gain, but estimates were imprecise and not statistically significant.We found no associations between total or early pregnancy weight gain and stillbirth across the range of weight gain experienced by most women.There was no association between weight gain during pregnancy and stillbirth among most women.
| S-EPMC6032856 | biostudies-other
Project description:Histological chorioamnionitis (HCA) is an established marker of ascending infection, a major cause of preterm birth. No studies have characterised the global change in expression of genes involved in the toll-like receptor (TLR) signalling pathways in the presence of HCA in the setting of preterm birth (pHCA). Fetal membranes were collected immediately after delivery and underwent histological staging for inflammation to derive 3 groups; term spontaneous labour without HCA (n = 9), preterm birth <34 weeks gestation without HCA (n = 8) and pHCA <34 weeks (n = 12). Profiling arrays ran in triplicate for each group were used to determine the expression of 84 genes associated with TLR signalling and screen for genes of interest (fold change >2; p<0.1). Expression of identified genes was validated individually for all samples, relative to GAPDH, using RT-PCR. Expression of TLR 1, TLR 2, lymphocyte antigen 96, interleukin 8 and Interleukin-1 receptor-associated kinase-like 2 was increased in pHCA (p<0.05). Degree of expression was positively associated with histological staging of both maternal and fetal inflammation (p<0.05). The inflammatory expression profile at the maternal/fetal interface associated with pHCA, a reflection of ascending infection, is extremely heterogeneous suggesting polymicrobial involvement with activation of a common pathway. Antagonism of TLR 1 and TLR 2 signalling in this setting warrants further assessment.
| S-EPMC4429010 | biostudies-literature
Project description:BackgroundChorioamnionitis is associated with various neonatal short- and long-term morbidities. The effect of chorioamnionitis on premature children's outcomes remains controversial. The aim of this study is to investigate the relationship between histological chorioamnionitis (HCA) and physiological development, wheezing, and atopic diseases in preterm children.MethodsSingleton, preterm children (< 34 weeks), whose mother underwent pathological placental examinations, were retrospectively enrolled and the outcomes were assessed at 24-40 months during follow-up. Wheezing and atopic diseases including eczema, food allergies, and allergic rhinitis were screened by a questionnaire along with medical diagnosis. Anthropometric indexes and blood pressure were measured. Cognitive and behavioural developments were assessed by the Gesell Development and Diagnosis Scale. Blood IgE and routine examination were analyzed with venous blood and serum metabolomic profiling was assessed via liquid chromatography-mass spectrometry (LC-MS). A multivariate logistic regression model was used to estimate the association between HCA and the current outcomes.ResultsAmong the 115 enrolled children, 47 were exposed to HCA. The incidence of wheezing was significantly higher in children exposed to HCA, as 38.30% of children who were exposed to HCA and 16.18% of children who were not had been diagnosed with wheezing. After adjusting for related confounders in the multivariate logistic regression model, there remained a 2.72-fold increased risk of wheezing in children with HCA (adjusted odds ratio, aOR, 2.72; 95% confidence interval, 1.02-7.23). Moreover, 163 differential metabolites, such as butanoic acid, annotemoyin 1 and charine, were identified in the HCA exposed children's serum. Enrichment analysis revealed that these compounds participated in diverse key metabolomic pathways relating to physical and neuro- developments, including glycerophospholipid, alpha-linolenic acid and choline metabolisms. There were no significant differences in atopic diseases, serum IgE, eosinophils' level, anthropometric indexes, blood pressure, or cognitive or behavioural developments between the two groups.ConclusionHCA exposure is associated with an increased risk of wheezing in preterm children less than 34 gestational weeks.
| S-EPMC7919088 | biostudies-literature
Project description:Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA.Gestational age-, birth weight-, delivery mode- and sex- matched (1:2) preterm neonates (< 35 weeks' gestation) born to mothers with or without HCA were enrolled from an observational study. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic analysis was performed on urine samples non-invasively collected in the first 24 hours of life. Univariate analysis, partial least square discriminant analysis (PLS-DA) and its associated variable importance in projection (VIP) score were performed. The most affected metabolic pathways were examined by Metabolite Sets Enrichment Analysis (MSEA).Fifteen cases (mean GA 30.2 ± 3.8 weeks, mean BW 1415 ± 471.9 grams) and 30 controls (mean GA 30.2 ± 2.9 weeks, mean BW 1426 ± 569.8 grams) were enrolled. Following univariate analysis, 29 metabolites had a significantly different concentration between cases and controls. The supervised PLS-DA model confirmed a separation between the two groups. Only gluconic acid, an oxidation product of glucose, was higher in cases than in controls. All other VIP metabolites were more abundant in the control group. Glutamate metabolism, mitochondrial electron transport chain, citric acid cycle, galactose metabolism, and fructose and mannose degradation metabolism were the most significantly altered pathways (P < 0.01).For the first time, urinary metabolomics was able to discriminate neonates born to mothers with and without HCA. The identification of specifically altered metabolic pathways may be helpful in understanding metabolic derangement following chorioamnionitis.
| S-EPMC5718427 | biostudies-literature
Project description:BackgroundStillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.Methods and findingsWe conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.ConclusionsStillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies. Please see later in the article for the Editors' Summary.
| S-EPMC3995658 | biostudies-literature
Project description:BackgroundHousehold surveys remain important sources of stillbirth data, but omission and misclassification are common. Classifying adverse pregnancy outcomes as stillbirths requires accurate reporting of vital status at birth and gestational age or birthweight for every pregnancy. Further categorisation, e.g. by sex, or timing (intrapartum/antepartum) improves data to understand and prevent stillbirth.MethodsWe undertook a cross-sectional population-based survey of women of reproductive age in five health and demographic surveillance system sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). All women answered a full birth history with pregnancy loss questions (FBH+) or a full pregnancy history (FPH). A sub-sample across both groups were asked additional stillbirth questions. Questions were evaluated using descriptive measures. Using an interpretative paradigm and phenomenology methodology, focus group discussions with women exploring barriers to reporting birthweight for stillbirths were conducted. Thematic analysis was guided by an a priori codebook.ResultsOverall 69,176 women reported 98,483 livebirths (FBH+) and 102,873 pregnancies (FPH). Additional questions were asked for 1453 stillbirths, 1528 neonatal deaths and 12,620 surviving children born in the 5 years prior to the survey. Completeness was high (> 99%) for existing FBH+/FPH questions on signs of life at birth and gestational age (months). Discordant responses in signs of life at birth between different questions were common; nearly one-quarter classified as stillbirths on FBH+/FPH were reported born alive on additional questions. Availability of information on gestational age (weeks) (58.1%) and birthweight (13.2%) was low amongst stillbirths, and heaping was common. Most women (93.9%) were able to report the sex of their stillborn baby. Response completeness for stillbirth timing (18.3-95.1%) and estimated proportion intrapartum (15.6-90.0%) varied by question and site. Congenital malformations were reported in 3.1% stillbirths. Perceived value in weighing a stillborn baby varied and barriers to weighing at birth a nd knowing birthweight were common.ConclusionsImproving stillbirth data in surveys will require investment in improving the measurement of vital status, gestational age and birthweight by healthcare providers, communication of these with women, and overcoming reporting barriers. Given the large burden and effect on families, improved data must be made available to end preventable stillbirths.
| S-EPMC7869203 | biostudies-literature
Project description:Background: Stillbirth rates are high and represent a substantial proportion of the under-5 mortality in low and middle-income countries (LMIC). In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented cause of stillbirths or the trends in rate of stillbirth over time.Methods: We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, Democratic Republic of Congo, India, Pakistan, and Guatemala). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Cause of stillbirth was assigned by algorithm.Results: From 2010 through 2018, 573,148 women were enrolled with delivery data obtained. Of the 552,547 births that reached 500?g or 20?weeks gestation, 15,604 were stillbirths; a rate of 28.2 stillbirths per 1000 births. The stillbirth rates were 19.3 in the Guatemala site, 23.8 in the African sites, and 33.3 in the Asian sites. Specifically, stillbirth rates were highest in the Pakistan site, which also documented a substantial decrease in stillbirth rates over the study period, from 56.0 per 1000 (95% CI 51.0, 61.0) in 2010 to 44.4 per 1000 (95% CI 39.1, 49.7) in 2018. The Nagpur, India site also documented a substantial decrease in stillbirths from 32.5 (95% CI 29.0, 36.1) to 16.9 (95% CI 13.9, 19.9) per 1000 in 2018; however, other sites had only small declines in stillbirth over the same period. Women who were less educated and older as well as those with less access to antenatal care and with vaginal assisted delivery were at increased risk of stillbirth. The major fetal causes of stillbirth were birth asphyxia (44.0% of stillbirths) and infectious causes (22.2%). The maternal conditions that were observed among those with stillbirth were obstructed or prolonged labor, antepartum hemorrhage and maternal infections.Conclusions: Over the study period, stillbirth rates have remained relatively high across all sites. With the exceptions of the Pakistan and Nagpur sites, Global Network sites did not observe substantial changes in their stillbirth rates. Women who were less educated and had less access to antenatal and obstetric care remained at the highest burden of stillbirth.Study registration: Clinicaltrials.gov (ID# NCT01073475).
| S-EPMC7706249 | biostudies-literature
Project description:BackgroundHousehold surveys remain important sources of maternal and child health data, but until now, standard surveys such as Demographic and Health Surveys (DHS) have not collected information on maternity care for women who have experienced a stillbirth. Thus, nationally representative data are lacking to inform programmes to address the millions of stillbirths which occur annually.MethodsThe EN-INDEPTH population-based survey of women of reproductive age was undertaken in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). All women answered a full birth history with additional questions on pregnancy losses (FBH+) or full pregnancy history (FPH). A sub-sample, including all women reporting a recent stillbirth or neonatal death, was asked additional maternity care questions. These were evaluated using descriptive measures. Associations between stillbirth and maternal socio-demographic characteristics, babies' characteristics and maternity care use were assessed using a weighted logistic regression model for women in the FBH+ group.ResultsA total of 15,591 women reporting a birth since 1 January 2012 answered maternity care questions. Completeness was very high (> 99%), with similar proportions of responses for both live and stillbirths. Amongst the 14,991 births in the FBH+ group, poorer wealth status, higher parity, large perceived baby size-at-birth, preterm or post-term birth, birth in a government hospital compared to other locations and vaginal birth were associated with increased risk of stillbirth after adjusting for potential confounding factors. Regarding association with reported postnatal care, women with a stillbirth were more likely to report hospital stays of > 1 day. However, women with a stillbirth were less likely to report having received a postnatal check compared to those with a live birth.ConclusionsWomen who had experienced stillbirth were able to respond to questions about pregnancy and birth, and we found no reason to omit questions to these women in household surveys. Our analysis identified several potentially modifiable factors associated with stillbirth, adding to the evidence-base for policy and action in low- and middle-income contexts. Including these questions in DHS-8 would lead to increased availability of population-level data to inform action to end preventable stillbirths.
| S-EPMC7869205 | biostudies-literature