Dataset Information

Previous miscarriage and the subsequent risk of preterm birth in Scotland, 1980-2008: a historical cohort study.

ABSTRACT:

Objective

To determine whether the relationship between previous miscarriage and risk of preterm birth changed over the period 1980-2008, and to determine whether the pattern varied according to the cause of the preterm birth.

Design

Linked birth databases.

Setting

All Scottish NHS hospitals.

Population

A total of 732 719 nulliparous women with a first live birth between 1980 and 2008.

Methods

Risk was estimated using logistic regression.

Main outcome measures

Preterm birth, subdivided by cause (spontaneous, induced with a diagnosis of pre-eclampsia, or induced without a diagnosis of pre-eclampsia) and severity [extreme (24-28 weeks of gestation), moderate (29-32 weeks of gestation), and mild (33-36 weeks of gestation)].

Results

Consistent with previous studies, previous miscarriage was associated with an increased risk of all-cause preterm birth (adjusted odds ratio, aOR 1.26; 95% confidence interval, 95% CI 1.22-1.29). This arose from associations with all subtypes. The strongest association was found with extreme preterm birth (aOR 1.73; 95% CI 1.57-1.90). Risk increased with the number of miscarriages. Women with three or more miscarriages had the greatest risk of all-cause preterm birth (aOR 2.14; 95% CI 1.93-2.38), and the strongest association was with extreme preterm birth (aOR 3.87; 95% CI 2.85-5.26). The strength of the association between miscarriage and preterm birth decreased from 1980 to 2008. This was because of weakening associations with spontaneous preterm birth and induced preterm birth without a diagnosis of pre-eclampsia.

Conclusions

The association between a prior history of miscarriage and the risk of preterm birth declined in Scotland over the period 1980-2008. We speculate that changes in the methods of managing incomplete termination of pregnancy might explain the trend, through reduced cervical damage.

SUBMITTER: Oliver-Williams C

PROVIDER: S-EPMC4611958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNumerous studies have demonstrated that therapeutic termination of pregnancy (abortion) is associated with an increased risk of subsequent preterm birth. However, the literature is inconsistent, and methods of abortion have changed dramatically over the last 30 years. We hypothesized that the association between previous abortion and the risk of preterm first birth changed in Scotland between 1 January 1980 and 31 December 2008.Methods and findingsWe studied linked Scottish national databases of births and perinatal deaths. We analysed the risk of preterm birth in relation to the number of previous abortions in 732,719 first births (?24 wk), adjusting for maternal characteristics. The risk (adjusted odds ratio [95% CI]) of preterm birth was modelled using logistic regression, and associations were expressed for a one-unit increase in the number of previous abortions. Previous abortion was associated with an increased risk of preterm birth (1.12 [1.09-1.16]). When analysed by year of delivery, the association was strongest in 1980-1983 (1.32 [1.21-1.43]), progressively declined between 1984 and 1999, and was no longer apparent in 2000-2003 (0.98 [0.91-1.05]) or 2004-2008 (1.02 [0.95-1.09]). A statistical test for interaction between previous abortion and year was highly statistically significant (p<0.001). Analysis of data for abortions among nulliparous women in Scotland 1992-2008 demonstrated that the proportion that were surgical without use of cervical pre-treatment decreased from 31% to 0.4%, and that the proportion of medical abortions increased from 18% to 68%.ConclusionsPrevious abortion was a risk factor for spontaneous preterm birth in Scotland in the 1980s and 1990s, but the association progressively weakened and disappeared altogether by 2000. These changes were paralleled by increasing use of medical abortion and cervical pre-treatment prior to surgical abortion. Although it is plausible that the two trends were related, we could not test this directly as the data on the method of prior abortions were not linked to individuals in the cohort. However, we speculate that modernising abortion methods may be an effective long-term strategy to reduce global rates of preterm birth.

Project description:INTRODUCTION:Preterm birth is closely associated with altered brain development and is a leading cause of neurodevelopmental, cognitive and behavioural impairments across the life course. We aimed to investigate neuroanatomic variation and adverse outcomes associated with preterm birth by studying a cohort of preterm infants and controls born at term using brain MRI linked to biosamples and clinical, environmental and neuropsychological data. METHODS AND ANALYSIS:Theirworld Edinburgh Birth Cohort is a prospective longitudinal cohort study at the University of Edinburgh. We plan to recruit 300 infants born at <33 weeks of gestational age (GA) and 100 healthy control infants born after 37 weeks of GA. Multiple domains are assessed: maternal and infant clinical and demographic information; placental histology; immunoregulatory and trophic proteins in umbilical cord and neonatal blood; brain macrostructure and microstructure from structural and diffusion MRI (dMRI); DNA methylation; hypothalamic-pituitary-adrenal axis activity; social cognition, attention and processing speed from eye tracking during infancy and childhood; neurodevelopment; gut and respiratory microbiota; susceptibility to viral infections; and participant experience. Main analyses include creation of novel methods for extracting information from neonatal structural and dMRI, regression analyses of predictors of brain maldevelopment and neurocognitive outcome associated with preterm birth, and determination of the quantitative predictive performance of MRI and other early life factors for childhood outcome. ETHICS AND DISSEMINATION:Ethical approval has been obtained from the National Research Ethics Service (NRES), South East Scotland Research Ethics Committee (NRES numbers 11/55/0061 and 13/SS/0143 (phase I) and 16/SS/0154 (phase II)), and NHS Lothian Research and Development (2016/0255). Results are disseminated through open access journals, scientific meetings, social media, newsletters anda study website (www.tebc.ed.ac.uk), and we engage with the University of Edinburgh public relations and media office to ensure maximum publicity and benefit.

Project description:ObjectivesTo evaluate the association between thyroid autoantibodies and miscarriage and preterm birth in women with normal thyroid function. To assess the effect of treatment with levothyroxine on pregnancy outcomes in this group of women.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, Cochrane Library, and SCISEARCH (inception-2011) without any language restrictions. We used a combination of key words to generate two subsets of citations, one indexing thyroid autoantibodies and the other indexing the outcomes of miscarriage and preterm birth.Study selectionStudies that evaluated the association between thyroid autoantibodies and pregnancy outcomes were selected in a two stage process. Two reviewers selected studies that met the predefined and explicit criteria regarding population, tests, and outcomes.Data synthesisOdds ratios from individual studies were pooled separately for cohort and case-control studies with the random effects model.Results30 articles with 31 studies (19 cohort and 12 case-control) involving 12,126 women assessed the association between thyroid autoantibodies and miscarriage. Five studies with 12,566 women evaluated the association with preterm birth. Of the 31 studies evaluating miscarriage, 28 showed a positive association between thyroid autoantibodies and miscarriage. Meta-analysis of the cohort studies showed more than tripling in the odds of miscarriage with the presence of thyroid autoantibodies (odds ratio 3.90, 95% confidence interval 2.48 to 6.12; P < 0.001). For case-control studies the odds ratio for miscarriage was 1.80, 1.25 to 2.60; P = 0.002). There was a significant doubling in the odds of preterm birth with the presence of thyroid autoantibodies (2.07, 1.17 to 3.68; P = 0.01). Two randomised studies evaluated the effect of treatment with levothyroxine on miscarriage. Both showed a fall in miscarriage rates, and meta-analysis showed a significant 52% relative risk reduction in miscarriages with levothyroxine (relative risk 0.48, 0.25 to 0.92; P=0.03). One study reported on the effect of levothyroxine on the rate of preterm birth, and noted a 69% relative risk reduction (0.31, 0.11 to 0.90).ConclusionThe presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.

Project description:ObjectiveTo investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound.MethodsThis was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery.ResultsBetween 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth.ConclusionsCervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Project description:Background : No universal demarcation of gestational age distinguishes miscarriage and stillbirth or extreme preterm birth (exPTB). This study provides a synopsis of outcome between 22 to <28 weeks gestation from a low resource setting. Methods : A retrospective record review of a population on the Thailand-Myanmar border was conducted. Outcomes were classified as miscarriage, late expulsion of products between 22 to < 28 weeks gestation with evidence of non-viability (mostly ultrasound absent fetal heart beat) prior to 22 weeks; or exPTB (stillbirth/live born) between 22 to < 28 weeks gestation when the fetus was viable at ≥22 weeks. Termination of pregnancy and gestational trophoblastic disease were excluded. Results : From 1995-2015, 80.9% (50,046/ 61,829) of registered women had a known pregnancy outcome, of whom 99.8% (49,931) had a known gestational age. Delivery between 22 to <28 weeks gestation included 0.9% (472/49,931) of pregnancies after removing 18 cases (3.8%) who met an exclusion criteria. Most pregnancies had an ultrasound: 72.5% (n=329/454); 43.6% (n=197) were classified as miscarriage and 56.4% (n=257) exPTB. Individual record review of miscarriages estimated that fetal death had occurred at a median of 16 weeks, despite late expulsion between 22 to <28 weeks. With available data (n=252, 5 missing) the proportion of stillbirth was 47.6% (n=120), congenital abnormality 10.5% (24/228, 29 missing) and neonatal death was 98.5% (128/131, 1 missing). Introduction of ultrasound was associated with a 2-times higher odds of classification of outcome as exPTB rather than miscarriage. Conclusion : In this low resource setting few (<1%) pregnancy outcomes occurred in the 22 to <28 weeks gestational window; four in ten were miscarriage (late expulsion) and neonatal mortality approached 100%. In the scale-up to preventable newborns deaths (at least initially) greater benefits will be obtained by focusing on the viable newborns of ≥ 28 weeks gestation.

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Project description:IntroductionThe global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix-related proteins (procollagen, osteopontin and IL-33), and of cytokines (IL-19, IL-6, IL-20, TNFα, TGFβ, and IL-1β) in asymptomatic women with and without subsequent spontaneous preterm delivery.Material and methodsWe used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks' gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad-range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double-blind, placebo-controlled trial to perform a nested case-control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix-related proteins and cytokines measured by immunoassays were compared for two study groups.Clinicaltrialsgov: NCT00718705.ResultsBetween July 2008 and July 2011, in 12 maternal-fetal medicine centers in France, 166 women with available PCR-negative amniotic fluid samples were retained for the analysis. Concentrations of procollagen, osteopontin, IL-19, IL-6, IL-20, IL-33, TNFα, TGFβ, and IL-1β were compared between the 37 who gave birth preterm and the 129 women with full-term delivery. Amniotic fluid levels of procollagen, osteopontin, IL-19, IL-33, and TNFα were significantly higher in the preterm than the full-term group. IL-6, IL-20, TGFβ, and IL-1β levels did not differ between the groups.ConclusionsIn amniotic fluid 16 S rDNA PCR negative samples obtained during second-trimester amniocentesis, extracellular matrix-related protein concentrations (procollagen, osteopontin and IL-33), together with IL-19 and TNFα, were observed higher at this time in cases of later spontaneous preterm birth.