High Risk Of PTB Research Articles

Gestation-dependent increase in cervicovaginal pro-inflammatory cytokines and cervical extracellular matrix proteins is associated with spontaneous preterm delivery within 2 weeks of index assessment in South African women.

Inflammation-induced remodelling of gestational tissues that underpins spontaneous preterm birth (sPTB, delivery < 37 weeks' gestation) may vary by race and context. To explore relationships between markers of these pathological processes, we (a) characterised the cervicovaginal fluid (CVF) cytokine profiles of pregnant South African women at risk of PTB; (b) determined CVF matrix-metalloproteinase-9 (MMP-9) and its regulator tissue inhibitor of metalloproteinase-1 (TIMP-1); and (c) explored the predictive potential of these markers for sPTB. The concentrations of 10 inflammatory cytokines and MMP-9 and TIMP-1 were determined by ELISA in CVF samples from 47 non-labouring women at high risk of PTB. We studied CVF sampled at three gestational time points (GTPs): GTP1 (20-22 weeks, n = 37), GTP2 (26-28 weeks, n = 40), and GTP3 (34-36 weeks, n = 29) and analysed for changes in protein concentrations and predictive capacities (area under the ROC curve (AUC) and 95% confidence interval (CI)) for sPTB. There were 11 (GTP1), 13 (GTP2), and 6 (GTP3) women who delivered preterm within 85.3 ± 25.9, 51.3 ± 15.3, and 11.8 ± 7.5 (mean ± SD) days after assessment, respectively. At GTP1, IL-8 was higher (4-fold, p = 0.02), whereas GM-CSF was lower (~1.4-fold, p = 0.03) in the preterm compared with term women with an average AUC = 0.73. At GTP2, IL-1β (18-fold, p < 0.0001), IL-8 (4-fold, p = 0.03), MMP-9 (17-fold, p = 0.0007), MMP-9/TIMP-1 ratio (9-fold, p = 0.004), and MMP-9/GM-CSF ratio (87-fold, p = 0.005) were higher in preterm compared with term women with an average AUC = 0.80. By contrast, IL-10 was associated with term delivery with an AUC (95% CI) = 0.75 (0.55-0.90). At GTP3, IL-1β (58-fold, p = 0.0003), IL-8 (12-fold, p = 0.002), MMP-9 (296-fold, p = 0.03), and TIMP-1 (35-fold, p = 0.01) were higher in preterm compared with term women with an average AUC = 0.85. Elevated IL-1β was associated with delivery within 14 days of assessment with AUC = 0.85 (0.67-0.96). Overall, elevated MMP-9 at GTP3 had the highest (13.3) positive likelihood ratio for distinguishing women at risk of sPTB. Lastly, a positive correlation between MMP-9 and TIMP-1 at all GTPs (ρ ≥ 0.61, p < 0.01) for women delivering at term was only observed at GTP1 for those who delivered preterm (ρ = 0.70, p < 0.03). In this cohort, sPTB is associated with gestation-dependent increase in pro-inflammatory cytokines, decreased IL-10 and GM-CSF, and dysregulated MMP-9-TIMP-1 interaction. Levels of cytokine (especially IL-1β) and ECM remodelling proteins rise significantly in the final 2 weeks before the onset of labour when sPTB is imminent. The signalling mechanisms for these ECM remodelling observations remain to be elucidated.

Assessment of cervical softening and the prediction of preterm birth (STIPP): protocol for a prospective cohort study

IntroductionPreterm birth (PTB) is among the leading causes of perinatal and childhood morbidity and mortality. Therefore, accurate identification of pregnant women at high risk of PTB is key to enable...

The Western Australian preterm birth prevention initiative: a whole of state singleton pregnancy cohort study showing the need to embrace alternative models of care for Aboriginal women

BackgroundPreterm birth (PTB) is the greatest cause of mortality and morbidity in children up to five years of age globally. The Western Australian (WA) PTB Prevention Initiative, the world’s first whole-of-population whole-of-state program aimed at PTB prevention, was implemented across WA in 2014.MethodsWe conducted a prospective population-based cohort study using pregnancy data for singleton births in WA from 2009 to 2019. Logistic regression using the last full year before the Initiative (2013) as the reference, and run charts were used to examine changes in PTB rates compared to pre-Initiative levels, by gestational age group, hospital type, low and high risk of PTB in mid-pregnancy, and onset of labour (spontaneous/medically initiated). Analyses were stratified by Aboriginal and non-Aboriginal maternal ethnicity.ResultsAmongst non-Aboriginal women, there was initially a reduction in the PTB rate across the state, and in recent years it returned to pre-Initiative levels. Amongst Aboriginal women there was a small, non- significant reduction in the state-wide PTB rate in the first three years of the Initiative, followed by a rise in recent years. For non-Aboriginal women, the reduction in the rate of PTB at the tertiary centre was sustained and improved further for women of all risk levels and onsets of labour. This reduction was not observed for Aboriginal women giving birth at the tertiary centre, amongst whom there was an increase in the PTB rate overall and in all subgroups, with the exception of medically initiated PTB. Amongst Aboriginal women the PTB rate has also increased across the state. At non-tertiary hospitals there was a large increase in PTB amongst both Aboriginal and non-Aboriginal women, largely driven by medically initiated late PTB. Maternal risk factors cannot account for this increase.ConclusionsThe reduction in PTB rates amongst non-Aboriginal women at the state’s tertiary hospital demonstrates that with the right strategies, PTB can be reduced. A sustained collaborative model is required to realise this success in non-tertiary hospitals. The series of interventions was of limited use in Aboriginal women, and future efforts will need to be directed at strategies more likely to be successful, such as midwifery continuity of care models, with Aboriginal representation in the healthcare workforce.

A project to validate the GLU test for preterm birth prediction in First Nations women

The protocol described in the present article aims to validate the GLU test, a test of mid-pregnancy vaginal microbiome, for PTB risk prediction in pregnant First Nations women. Preterm birth (PTB; birth before 37 completed weeks gestation) is associated with a higher risk of adverse neonatal outcomes. First Nations communities are affected by increasing PTB rates, highest in remote communities, reaching 23%. Being able to predict women at high risk of PTB is one of the greatest challenges of our time. No reliable clinical predictors of PTB risk currently exist, beyond a previous history. Spontaneous PTB (sPTB) is highly associated with microbial infection. Recently, a Western Australian research team developed an innovative mid-pregnancy vaginal microbial DNA test, the ‘Gardnerella, Lactobacillus, Ureaplasma’ (GLU) test, capable of predicting up to 45% of sPTB cases. However, this test has only been validated in predominantly Caucasian pregnant women. The protocol described aims to validate the GLU test in pregnant First Nations women and where applicable, make modifications to this test to improve sensitivity and specificity within this population.

Rapid quality improvement in a preterm birth clinic care pathway during the COVID-19 pandemic

BackgroundPreterm birth (PTB) occurs in 8% of births in the UK. At Imperial College Healthcare NHS Trust, our PTB prevention clinic manages the care of approximately 1000 women/year. Women referred...

Spatial inequality, characteristics of internal migration, and pulmonary tuberculosis in China, 2011\u20132017: a spatial analysis

BackgroundHuman migration facilitate the spread of tuberculosis (TB). Migrants face an increased risk of TB infection. In this study, we aim to explore the spatial inequity of sputum smear-positive pulmonary TB (SS + PTB) in China; and the spatial heterogeneity between SS + PTB and internal migration.MethodsNotified SS + PTB cases in 31 provinces in mainland China were obtained from the national web-based PTB surveillance system database. Internal migrant data were extracted from the report on China’s migrant population development. Spatial autocorrelations were explored using the global Moran’s statistic and local indicators of spatial association. The spatial variation in temporal trends was performed using Kulldorff’s scan statistic. Fixed effect and spatial autoregressive models were used to explore the spatial inequity between SS + PTB and internal migration.ResultsA total of 2 380 233 SS + PTB cases were reported in China between 2011 and 2017, of which, 1 716 382 (72.11%) were male and 663 851 (27.89%) were female. Over 70% of internal migrants were from rural households and had lower income and less education. The spatial variation in temporal trend results showed that there was an 9.9% average annual decrease in the notification rate of SS + PTB from 2011 to 2017; and spatial clustering of SS + PTB cases was mainly located in western and southern China. The spatial autocorrelation results revealed spatial clustering of internal migration each year (2011–2017), and the clusters were stable within most provinces. Internal emigration, urban-to-rural migration and GDP per capita were significantly associated with SS + PTB, further, internal emigration could explain more variation in SS + PTB in the eastern region in mainland. However, internal immigration and rural-to-urban migration were not significantly associated with SS + PTB across China.ConclusionsOur study found the spatial inequity between SS + PTB and internal migration. Internal emigration, urban-to-rural migration and GDP per capita were statistically associated with SS + PTB; the negative association was identified between internal emigration, urban-to-rural migration and SS + PTB. Further, we found those migrants with lower income and less education, and most of them were from rural households. These findings can help stakeholders to implement effective PTB control strategies for areas at high risk of PTB and those with high rates of internal migration.

Adequate antenatal care and ethnicity affect preterm birth in pregnant women living in the tropical rainforest of Suriname

BackgroundAdequate antenatal care (ANC) services are key for early identification of pregnancy related risk factors and maintaining women’s health during pregnancy. This study aimed to assess the influence of ANC provided by the Medical Mission Primary Health Care Suriname (MMPHCS) and of ethnicity on adverse birth outcomes in Tribal and Indigenous women living in Suriname’s remote tropical rainforest interior.MethodFrom April 2017 to December 2018 eligible Tribal and Indigenous women with a singleton pregnancy that received ANC from MMPHCS were included in the study. Data on low birth weight (LBW < 2500 g), preterm birth (PTB < 37 weeks), low Apgar score (< 7 at 5 min), parity (≤1 vs. > 1) and antenatal visits utilization (≥8 vs. < 8) in 15 interior communities were retrospectively analyzed using descriptive statistics, crosstabs and Fisher’s exact tests.ResultsA total of 204 women were included, 100 (49%) were Tribal, mean age was 26 ± 7.2 years and 126 women (62%) had 8 or more ANC visits. One participant had a miscarriage; 22% had adverse birth outcomes: 16 (7.9%) LBW and 30 (14.8%) PTB; 7 women had a child with both PTB and LBW; 5 women had stillbirths. None of the newborns had low Apgar scores. Maternal age, ethnicity, ANC and parity were associated with PTB (χ2 = 8,75, p = 0.003, χ2 = 4,97, p = 0.025, χ2 = 17,45, p < 0.001, χ2 = 11,93, p < 0.001 respectively).ConclusionDespite an almost 100% study adherence over one fifth of women that received ANC in the interior of Suriname had adverse birth outcomes, in particular PTB and LBW. Younger nulliparous Indigenous women with less than the recommended 8 ANC visits had a higher risk for PTB. The rate of adverse birth outcomes highlights the need for further research to better assess factors influencing perinatal outcomes and to put strategies in place to improve perinatal outcomes. Exposure assessment of this sub-cohort and neurodevelopment testing of their children is ongoing and will further inform on potential adverse health effects associated with environmental exposures including heavy metals such as mercury and lead.

Driving Factors of Preterm Birth Risk in Adolescents.

Objective We examined rates of spontaneous and indicated preterm births (S-PTB and I-PTB, respectively) and clinical risk factors for PTB in adolescents. Study Design This is a population-based, retrospective cohort using 2012 U.S. natality data of nulliparous women who delivered a nonanomalous singleton birth between 20 and 42 weeks' gestation. Maternal age included <16, 16 to 19.9, and ≥20 years. Rates of total, S-PTB, and I-PTB were compared across age groups. Multinomial logistic regression tested clinical risk factors for S-PTB. Results In 1,342,776 pregnancies, adolescents were at higher risk for PTB than adults. The rate of total PTB was highest in young adolescents at 10.6%, decreased to 8.3% in older adolescents, and 7.8% in adults. The proportion of S-PTB was highest in the youngest adolescents and decreased toward adulthood; the proportion of I-PTB remained stable across age groups. Risk factors for S-PTB in adolescents included Asian race, underweight body mass index (BMI), and poor gestational weight gain (GWG). In all age groups, carrying a male fetus showed a significant increased S-PTB, and Women, Infants, and Children's (WIC) participation was associated with a significantly decreased risk. Conclusion The higher risk for PTB in adolescents is driven by an increased risk for S-PTB. Low BMI and poor GWG may be potentially modifiable risk factors. Condensation Adolescents have a higher risk for spontaneous PTB than adult women, and risk factors for spontaneous PTB may differ in adolescents.

Perinatal outcomes from preterm and early term births in a multicenter cohort of low risk nulliparous women

Preterm birth is the major contributor for neonatal and under-five years mortality rates and also accounts for a short- and long-term adverse consequences up to adulthood. Perinatal outcomes may vary according to lots of factors as preterm subtype, late prematurity, which account for the vast majority of cases, country and population characteristics. An under-recognition of the perinatal outcomes and its associated factors might have underpowered strategies to provide adequate care and prevent its occurrence. We aim to estimate the frequency of maternal and perinatal outcomes in women with different categories of preterm and term births, factors associated with poorer perinatal outcomes and related management interventions. A multicentre prospective cohort in five maternities in Brazil between 2015 and 2018. Nulliparous low-risk women with singletons were included. Comprehensive data were collected during three antenatal visits (at 19–21weeks, 27–29 weeks and 37–39 weeks). Maternal and perinatal outcomes were also collected according to maternal and neonatal medical records. Women who had spontaneous (sPTB) and provider-initiated (pi-PTB) preterm birth were compared to those who had term birth. Also, late preterm birth (after 34 weeks), and early term (37–38 weeks) were compared to full term birth (39–40 weeks). Bivariate analysis estimated risk ratios for maternal and adverse outcomes. Finally, a multivariate analysis was conducted to address factors independently associated with any adverse perinatal outcome (APO). In total, 1,165 women had outcome data available, from which 6.7% had sPTB, 4.0% had pi-PTB and 89.3% had a term birth. sPTB and pi-PTb were associated with poorer perinatal outcomes, as well as late sPTB, late pi-PTB and early term neonates. pi-PTB (RRadj 8.12, 95% CI [2.54–25.93], p-value 0.007), maternal weight gain between 20 and 27 weeks <p10 (RRadj 2.04, 95% CI [1.23–3.38], p-value 0.018) and participants from the Northeast centres (RRadj 2.35, 95% CI [1.11–4.95], p-value 0.034) were independently associated with APO. According to our findings, Brazil would benefit from strategies to more accurately identify women at higher risk for PTB, to promote evidenced-based decision in preterm and early term provider-initiated deliveries, and to prevent perinatal adverse outcomes.

The association between internal migration and pulmonary tuberculosis in China, 2005\u20132015: a spatial analysis

BackgroundInternal migration places individuals at high risk of contracting tuberculosis (TB). However, there is a scarcity of national-level spatial analyses regarding the association between TB and internal migration in China. In our research, we aimed to explore the spatial variation in cases of sputum smear-positive pulmonary TB (SS + PTB) in China; and the associations between SS + PTB, internal migration, socioeconomic factors, and demographic factors in the country between 2005 and 2015.MethodsReported cases of SS + PTB were obtained from the national PTB surveillance system database; cases were obtained at the provincial level. Internal migration data were extracted from the national population sampling survey and the census. Spatial autocorrelations were explored using the global Moran’s statistic and local indicators of spatial association. The spatial temporal analysis was performed using Kulldorff’s scan statistic. Fixed effects regression was used to explore the association between SS + PTB and internal migration.ResultsA total of 4 708 563 SS + PTB cases were reported in China between 2005 and 2015, of which 3 376 011 (71.7%) were male and 1 332 552 (28.3%) were female. There was a trend towards decreasing rates of SS + PTB notifications between 2005 and 2015. The result of global spatial autocorrelation indicated that there were significant spatial correlations between SS + PTB rate and internal migration each year (2005–2015). Spatial clustering of SS + PTB cases was mainly located in central and southern China and overlapped with the clusters of emigration. The proportions of emigrants and immigrants were significantly associated with SS + PTB. Per capita GDP and education level were negatively associated with SS + PTB. The internal migration flow maps indicated that migrants preferred neighboring provinces, with most migrating for work or business.ConclusionsThis study found a significant spatial autocorrelation between SS + PTB and internal migration. Both emigration and immigration were statistically associated with SS + PTB, and the association with emigration was stronger than that for immigration. Further, we found that SS + PTB clusters overlapped with emigration clusters, and the internal migration flow maps suggested that migrants from SS + PTB clusters may influence the TB epidemic characteristics of neighboring provinces. These findings can help stakeholders to implement effective PTB control strategies for areas at high risk of PTB and those with high rates of internal migrants.

CT FOR EARLY DIAGNOSIS OF SPUTUM-SMEAR NEGATIVE PULMONARY TB IN ENDEMIC POPULATIONS

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Early diagnosis of Tuberculosis (TB) is critical for prompt treatment and diagnostic dilemmas can delay appropriate treatment. We review 2 cases of sputum smear-negative pulmonary TB (SSN-pTB). CASE PRESENTATION: Case 1. A 57 year old Chinese man presented with haemoptysis. Radiology revealed a papillary thyroid carcinoma with severe extrinsic tracheal compression and infiltration. He received a total thyroidectomy. Although initial smear and molecular tests were negative on sputum, empiric TB treatment was started given tree-in-bud changes in the right upper lobe on CT. TB cultures from sputum and tracheal aspirates proved TB infection 6 weeks later. Case 2. A 34 year old Filipino pregnant lady presented with haemoptysis and near syncope. Ultrasound of calves were negative for deep venous thrombosis while CT pulmonary angiography revealed only left upper lobe tree in bud changes. Subsequent sputum studies were smear negative but molecular positive TB with culture conversion 2 months later. She was initiated on TB treatment with good outcomes. DISCUSSION: The diagnosis of pTB depends on clinical features and the decision to initiate treatment depends on the pre-test probability. Patients with sputum smear-negative pTB (SSN-pTB) pose as diagnostic dilemmas as they usually have mild symptoms or systemic manifestations. Culture conversion often requires 6-8 weeks to confirm the diagnosis hence losing valuable time for effective and early treatment. Although sputum TB smear and culture are the gold standards in diagnosing pTB, patients may not have sputum. While flexible fiberoptic bronchoscopy can increase the diagnostic yield of SSN-pTB this is invasive and bear risks of complications arising from anticipated difficult airways in both patients. Although empiric TB treatment can be initiated in younger patients with minimal adverse reactions as with the first patient, this cannot be similarly applied to the second patient given clear obstetric and gynaecological considerations to initiating TB treatment without diagnostic confirmation. Confirmation of pTB before initiating treatment is still ideal in either case. CT can be useful in the rapid diagnosis of pTB. Tree-in-bud appearance is the most significant association with active PTB in 24-33% of patients[1] with SSN-pTB. CT features suggestive of pTB reportedly have high sensitivity, specificity as well as positive- and negative- predictive values[2]. In particular, HRCT has been shown to predict the risk of PTB with good reproducibility [3]and is a good diagnostic tool to identify patients with high risk of pTB. CONCLUSIONS: It is important to consider and screen for TB in high risk patients especially if early diagnosis and subsequent treatment of TB is necessary. Tree-in-bud appearance on CT is highly suggestive of PTB in an endemic population and can be useful in the diagnosis of patients with SSN-pTB with difficulty expectorating sputum. Reference #1: Hatipoglu et al . Thorax 1996: 51: 397-402 Reference #2: JS park et al ERJ 2016 48 (60): PA3806 Reference #3: Nakanishi M et al. Eur J Radiol. 2010 Mar;73(3):545-50 DISCLOSURES: no disclosure on file for Kay See; No relevant relationships by Genevieve Tan, source=Web Response

Reducing the impact of preterm birth: Preterm birth commissioning in the United Kingdom.

Reducing preterm birth is a priority for Maternity and Children’s services. In the recent UK Department of Health publication ‘Safer Maternity Care’ the Secretary of State for Health aimed to achieve the national maternity safety ambition by pledging to reduce the rate of preterm birth from 8% to 6%. It was proposed that specialist preterm birth services should be established in the UK in order to achieve this aim. In response the Preterm Clinical Network has written Commissioning Guidance aimed to establish best practice pathways and agreed models of care to reduce variation nationally. They have been developed by clinical experts in the field, from within the UK, to provide recommendations for commissioning groups and to recommend pathways to organisations with the aim of reducing the incidence of preterm birth. Three key areas of care provision are focused on: prediction, prevention and preparation of women at high risk of PTB. This Expert Opinion, will summarise the Commissioning Guidance.

Lamellar bodies as a predictor of fetal lung maturity

Introduction: Respiratory disorders remain an important newborn complication. Currently, there have been alarming information about the impact of repeated courses (even one “resque” course) of RDS prophylaxis on the quality of health in childhood and adulthood. Therefore, the search for available tests to determine the fetal lungs maturity in women at high risk of PTB is an important practical problem. Lamellar bodies (LBCs) produced by type II pneumocytes and appearing in the amniotic fluid in 28–32 weeks may serve as a possible such potential marker.

P3-S7.12 Infections and interventions in pregnant women at high risk of preterm birth: a cohort study

BackgroundPreterm birth (PTB) accounts for 65% neonatal deaths and 50% neurological disability in children. Prior spontaneous PTB is the highest risk factor for subsequent PTB and is usually associated with...

Cervical length mid trimester in low risk women fails to predict the majority of pre term births

IntroductionPre term birth (PTB) is a leading course of morbidity and mortality. Prediction is possible but lacks sensitivity. Mid trimester ultrasound of cervical length (MCL) can identify women at high...