Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

Background Timely interventions in women presenting with preterm labour can substantially improve health outcomes for preterm babies. However, establishing such a diagnosis is very challenging, as signs and symptoms of preterm labour are common and can be nonspecific. We aimed to develop and externally validate a risk prediction model using concentration of vaginal fluid fetal fibronectin (quantitative fFN), in combination with clinical risk factors, for the prediction of spontaneous preterm birth and assessed its cost-effectiveness. Methods and findings Pregnant women included in the analyses were 22+0 to 34+6 weeks gestation with signs and symptoms of preterm labour. The primary outcome was spontaneous preterm birth within 7 days of quantitative fFN test. The risk prediction model was developed and internally validated in an individual participant data (IPD) meta-analysis of 5 European prospective cohort studies (2009 to 2016; 1,783 women; mean age 29.7 years; median BMI 24.8 kg/m2; 67.6% White; 11.7% smokers; 51.8% nulliparous; 10.4% with multiple pregnancy; 139 [7.8%] with spontaneous preterm birth within 7 days). The model was then externally validated in a prospective cohort study in 26 United Kingdom centres (2016 to 2018; 2,924 women; mean age 28.2 years; median BMI 25.4 kg/m2; 88.2% White; 21% smokers; 35.2% nulliparous; 3.5% with multiple pregnancy; 85 [2.9%] with spontaneous preterm birth within 7 days). The developed risk prediction model for spontaneous preterm birth within 7 days included quantitative fFN, current smoking, not White ethnicity, nulliparity, and multiple pregnancy. After internal validation, the optimism adjusted area under the curve was 0.89 (95% CI 0.86 to 0.92), and the optimism adjusted Nagelkerke R2 was 35% (95% CI 33% to 37%). On external validation in the prospective UK cohort population, the area under the curve was 0.89 (95% CI 0.84 to 0.94), and Nagelkerke R2 of 36% (95% CI: 34% to 38%). Recalibration of the model’s intercept was required to ensure overall calibration-in-the-large. A calibration curve suggested close agreement between predicted and observed risks in the range of predictions 0% to 10%, but some miscalibration (underprediction) at higher risks (slope 1.24 (95% CI 1.23 to 1.26)). Despite any miscalibration, the net benefit of the model was higher than “treat all” or “treat none” strategies for thresholds up to about 15% risk. The economic analysis found the prognostic model was cost effective, compared to using qualitative fFN, at a threshold for hospital admission and treatment of ≥2% risk of preterm birth within 7 days. Study limitations include the limited number of participants who are not White and levels of missing data for certain variables in the development dataset. Conclusions In this study, we found that a risk prediction model including vaginal fFN concentration and clinical risk factors showed promising performance in the prediction of spontaneous preterm birth within 7 days of test and has potential to inform management decisions for women with threatened preterm labour. Further evaluation of the risk prediction model in clinical practice is required to determine whether the risk prediction model improves clinical outcomes if used in practice. Trial registration The study was approved by the West of Scotland Research Ethics Committee (16/WS/0068). The study was registered with ISRCTN Registry (ISRCTN 41598423) and NIHR Portfolio (CPMS: 31277).

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“…Assessment of bias of studies included in the individual participant data meta-analysis. Risk of bias checklist adapted from(5). TableE.…”

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confidence: 99%

Development and validation of a risk prediction model of preterm birth for women with preterm labour symptoms (the QUIDS study): A prospective cohort study and individual participant data meta-analysis

et al. 2021

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“…Dexamethasone is a synthetic glucocorticoid that has been shown to disrupt glucose transport into cells, preventing proper breakdown of glucose and increased free glucose in the blood [24]. Dexamethasone is also frequently given antenatally to facilitate fetal lung maturation [25]. Our results show the combination of glucose and dexamethasone treatment provides a much tighter range of significantly elevated whole-body glucose values (Fig.…”

Section: Resultsmentioning

confidence: 77%

Section: Induction Of Hyperglycemia In Developing Zebrafish Via Glucose and Dexamethasone Exposurementioning

confidence: 99%

Embryonic hyperglycemia perturbs the development of specific retinal cell types, including photoreceptors

Titialii-Torres

Morris

2021

Preprint

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Chronic hyperglycemia has been linked to various long-term metabolic disruptions in adults, such as neuropathy, nephropathy, and diabetic retinopathy. According to the 2020 National Diabetes Statistics Report, 10.5% of the US population has diabetes and may be susceptible to long-term complications if blood glucose is not tightly regulated. Further, in 2018, 7.6% of US pregnancies were affected by gestational diabetes, with an average of 1-14% annually. During pregnancy, glucose can pass through the placental barrier, and plays an important role in fetal development and survival. However, excess maternal glucose can also result in diabetic embryopathy. While many studies have examined the teratogenic effects of maternal diabetes on fetal heart development, little is known about the consequences of maternal hyperglycemia on the development of the embryonic retina. To address this question, we investigated retinal cell type differentiation and survival in both a genetic and nutritional model of embryonic hyperglycemia in zebrafish. Strikingly, we found that hyperglycemic larvae displayed a significant reduction in rod and cone photoreceptors and horizontal cells, whereas other retinal neurons were not affected. We also observed signs of reactive gliosis in the retinal Müller cells, as well as increased reactive oxygen species (ROS) production in hyperglycemic retinas. Hyperglycemic larvae displayed altered expression of metabolism related genes and had a slower optokinetic response than normoglycemic larvae, indicating altered visual function. Further analysis of early events in retinogenesis revealed a delay in retinal cell differentiation at 48 hpf in hyperglycemic embryos, that coincided with an increase in reactive oxygen species. Taken together, our results suggest that embryonic hyperglycemia results in abnormal retinal cell development via altered timing of retinal cell differentiation and ROS production, which is accompanied by visual defects. As the population with diabetes continues to grow, it is imperative to pinpoint the effects of embryonic hyperglycemia on retinal development. Further studies using zebrafish models of hyperglycemia will allow us to understand the molecular mechanisms underlying these effects, which could aid in the development of therapeutic strategies.

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“…In our Hospital the ORACLE II study provided consistency in antibiotic treatments for PPROM, subjected to some variability until 2003 [ 22 ]. Benefits arising the use of corticosteroids to accelerate fetal lung maturation and reduce the risk of necrotizing enterocolitis and intraventricular hemorrhage cases of PPROM over 24 0/7 weeks are also important [ 23 , 24 , 25 ]. In our series, the latency period has been progressively extended over the years.…”

Section: Discussionmentioning

confidence: 99%

Obstetric and Perinatal Outcomes after Very Early Preterm Premature Rupture of Membranes (PPROM)-A Retrospective Analysis over the Period 2000–2020

et al. 2021

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Background and Objectives: Pre-term premature rupture of membranes (PPROM) responds for one third of preterm births, and it is associated with other complications that increase the risk of maternal or fetal poor outcome. To reduce uncertainty and provide accurate information to patients, the analysis of the large series is of great importance. In order to learn about the evolution over the time of the obstetric and perinatal outcomes in cases of PPROM at, or before, 28 weeks (very early PPROM) managed with an expectant/conservative protocol, we have designed the present study. Materials and Methods: We retrospectively studied all cases of very early PPROM attended in Malaga University Regional Hospital from 2000 to 2020. Results: Among 119888 deliveries assisted, 592 cases of PPROM occurred in pregnancies at or before 28 weeks (0.49% of all deliveries, 3.9% of all preterm births and 12.9% of all cases of PPROM). The mean duration of the latency period between PPROM and delivery was 13.5 days (range 0 to 88 days), enlarging over the years. The mean gestational age at delivery was 27 weeks (SD 2.9; range 17–34). The proportion of cesarean deliveries was 52.5%. The overall perinatal mortality rate was 26.5%, decreasing over the period with a significant correlation Pearson’s coefficient −0.128 (p < 0.05). Conclusions: In the period 2000–2020, there was an improvement in the outcomes of very early PPROM cases and perinatal mortality showed a clear trend to decrease.

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Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

Cited by 318 publications

References 126 publications

Development and validation of a risk prediction model of preterm birth for women with preterm labour symptoms (the QUIDS study): A prospective cohort study and individual participant data meta-analysis

Development and validation of a risk prediction model of preterm birth for women with preterm labour symptoms (the QUIDS study): A prospective cohort study and individual participant data meta-analysis

Embryonic hyperglycemia perturbs the development of specific retinal cell types, including photoreceptors

Obstetric and Perinatal Outcomes after Very Early Preterm Premature Rupture of Membranes (PPROM)-A Retrospective Analysis over the Period 2000–2020

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