Previous Preterm Birth Research Articles

Epigenetic Biomarker for Preeclampsia Associated Preterm Birth and Potential Preventative Medicine

Abstract Preterm birth has dramatically increased within the population (i.e., >10%) and preeclampsia is a significant sub-category of preterm birth. Currently, there are no practical clinical parameters or biomarkers which predict preeclampsia induced preterm birth. The current study investigates the potential use of epigenetic (DNA methylation) alterations as a maternal preeclampsia biomarker. Non-preeclampsia term births were compared to preeclampsia preterm births to identify DNA methylation differences (i.e., potential epigenetic biomarker). Maternal buccal cell cheek swabs were used as a marker cell for systemic epigenetic alterations in the individuals, which are primarily due to environmentally induced early life or previous generations impacts, and minimally impacted or associated with the disease etiology or gestation variables. A total of 389 differential DNA methylation regions (DMRs) were identified and associated with the presence of preeclampsia. The DMRs were genome-wide and were predominantly low CpG density (<2 CpG/100 bp). In comparison with a previous preterm birth buccal cell epigenetic biomarker there was a 15% (60 DMR) overlap, indicating the majority of the DMRs are unique for preeclampsia. Few previously identified preeclampsia genes have been identified, however, the DMRs had gene associations in the P13K-Akt signaling pathway and metabolic gene family, such as phospholipid signaling pathway. Preliminary validation of the DMR use as a potential maternal biomarker used a cross-validation analysis on the samples and provided a 78% accuracy. Although prospective expanded clinical trials in first trimester pregnancies and clinical comparisons are required, the current study provides the potential proof of concept a preeclampsia epigenetic biomarker may exist. The availability of a preeclampsia preterm birth maternal susceptibility biomarker may facilitate clinical management and allow preventative medicine approaches to identify and treat the preeclampsia condition prior to its occurrence.

Cervical cerclage vs cervical pessary in women with cervical insufficiency: A multicentric, open-label, randomised, controlled pilot trial [the CEPEIC trial]

ObjectiveCervical insufficiency accounts for 8 % of preterm births. Pessary and cerclage are considered preventive approaches for preterm birth. These interventions were compared in terms of reducing the prematurity rate in women with previous preterm birth, due to cervical insufficiency or due to having a short cervix in their current pregnancy. MethodsThis was a prospective, multicentric, open-label, randomised, pilot, controlled trial. Participants were women with singleton pregnancies who had previous preterm birth caused by cervical insufficiency or previous preterm birth and a short cervix [≤ 25 mm] in their current pregnancy. Women were randomised [1:1] to either cerclage or pessary. The primary outcome was to assess the feasibility of a trial on cervical pessary vs. cerclage to prevent preterm birth before 34 weeks in women with cervical insufficiency. As a secondary outcome, we studied the morbidity rate of the pessary versus the cerclage in women with cervical insufficiency and assessed the financial impact of using both devices in these women. The sample size was calculated based on the estimated population that we could potentially recruit: 60 women, 30 for each group, to ascertain whether the rate of preterm birth < 34 weeks of gestation may be reduced from 34 % to at least 27 % in the pessary group, as in the results obtained with the cerclage. ResultsNo significant differences in preterm birth < 34 weeks of gestation were observed in our study, although it was underpowered to detect these differences [the relative risk [RR] of PB < 34 weeks of gestation was 0.8 [95 % CI: 0.31–2.09, p = 0.888]. The rates of obstetric and perinatal complications were similar for both devices [15 cases in both groups, 50 % of cases [RR; 0.6–1.68; p = 1]. Cervical pessary had fewer secondary effects than the cerclage [less bleeding at insertion in the pessary group compared with cerclage, 1 case vs 14 cases, p < 0.001; less pain at removal in the pessary group compared with cerclage, 14 vs 22 cases. p = 0.042 and less bleeding, 2 cases vs. 10 cases, p = 0.027]. ConclusionsPessary does not seem less effective than cerclage, although these findings need to be confirmed in a larger randomised controlled trial. Pessary had fewer secondary effects than cerclage both at insertion and removal. SinopsisCervical pessary does not seem to be less effective than cerclage. Cervical pessary had fewer secondary effects than cerclage.

Indirect Effects of Neighbourhood Socioeconomic Status on Preterm Birth Risk in an Argentine Population.

Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to determine the indirect effects of neighbourhood socioeconomic status (NSES) on the risk of spontaneous PTB. We carried out a retrospective case-control study including sociodemographic and obstetric data of multigravid women who gave birth at a maternity hospital in Tucumán, Argentina, between 2005 and 2010: 949 women without previous PTB nor pregnancy loss who delivered at term and 552 who had spontaneous PTB. NSES was estimated from the Unsatisfied Basic Needs index of census data. Variables selected through penalised regressions were used to create a data-driven Bayesian network; then, pathways were identified and mediation analyses performed. Maternal age less than 20 years mediated part of the protective effect of high NSES on spontaneous PTB [natural indirect effect (NIE) -0.0125, 95% confidence interval (CI) (-0.0208, -0.0041)] and on few prenatal visits (< 5) [NIE - 0.0095, 95% CI (-0.0166, -0.0025)]. These pathways showed greater sensitivity to unobserved confounders that affect the variables mediator-outcome in the same direction, and exposure-mediator in the opposite direction. They did not show sensitivity to observed potential confounders, nor to the parameterization used to define NSES. Meanwhile, urinary tract infections showed a trend in mediating the effect of low NSES on spontaneous PTB [NIE 0.0044, 95% CI (-0.0006, 0.0093), P 0.0834]. High NSES has protective indirect effects on spontaneous PTB risk, mainly associated with a lower frequency of teenage pregnancy.

Maternal Risk Factors Associated with Preterm Birth: A Case Control Study.

Preterm birth is the child birth before 37 completed weeks .Prematurity is one of the leading causes of neonatal morbidity and mortality due to the complications associated with it. The objective of the study was to determine the maternal risk factors associated with all preterm birth in singleton pregnancy at National hospital. Hospital based unmatched case control study was conducted between March 2021 to December 2021 at National hospital, Thimphu, Bhutan. Case to control ratio was 1:2.Data were collected using interviewer -administered structured questionnaires. The collected data were entered into Epi-data and exported into SPSS for analysis. Independent variables with p-valves<0.05 in the univariate analysis were entered to multi variable logistic model to estimate the strength of association .P-valve <0.05 was considered significant. Total of 107 cases and 201 controls participated with a response rate of 95.95%.Multiple logistic regression showed that mothers with ANC follow ≤ four[aOR 9.58(7.36-28.86) ], previous history of preterm delivery [aOR 2.99(1.5-15.77) ], previous caesarean section [aOR 5.72(2.19-14.92)], prelabour rupture of membrane [aOR 8.67(3.78-19.73)], fetal growth restriction [aOR 7.28(2.11-25.11)] , and pre-eclampsia [aOR 10.99(6.75-85.29) were the risk factors positively associated with preterm birth . This study highlights that preeclampsia, number of antenatal care visits ≤ four, prelabour rupture of membrane, fetal growth restriction, previous caesarean section and previous preterm delivery were the risk factors for preterm birth. This show the need of early screening and prevention of preeclampsia, strengthening of antenatal care follow-up, and treatment of infection to prevent prelabour rupture of membrane, reducing primary caesarean section and more attention and care with previous preterm birth .

Risk factors for premature rupture of membranes in pregnant women: a systematic review and meta-analysis

ObjectiveTo identify risk factors for premature rupture of membranes (PROM) in pregnant women.DesignSystematic review and meta-analysis.Data sourcesWeb of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese...

Perinatal and neonatal outcomes of high-risk asymptomatic women from a specialist preterm birth surveillance clinic

ObjectivesTo report the perinatal outcomes of high-risk asymptomatic women who attended a specialist preterm surveillance clinic (PSC) to undergo screening for spontaneous preterm birth (PTB) in Ireland. MethodsSingle center, retrospective cohort study of asymptomatic high risk women who attended the PSC between January 2019 and December 2022. A comprehensive database of all patients who attended the clinic during the study period was constructed and analyzed. Overall outcomes were reported, and stratified per the occurrence of preterm or term birth. Iatrogenic PTBs were included in the outcome data. ResultsFollowing exclusions for loss-to-follow-up, 762 cases were analyzed, constituting 2262 PSC visits. Of those, 183 women were prescribed progesterone (24.0 %), and 100 women underwent cervical cerclage (13.1 %) to prevent spontaneous PTB. Overall, 2.4 %, 6.2 % and 18.6 % of participants gave birth prior to 30 weeks, 34 weeks, and 37 weeks, respectively. The median gestational age at birth for the entire cohort was 38.6 weeks (inter-quartile range (IQR) 37.2–39.6 weeks).Women who delivered < 37 weeks were significantly more likely to be smokers (p = 0.030), have a previous spontaneous PTB (p = 0.016), have multiple pregnancies (p < 0.001), type 1 or 2 diabetes (p = 0.044), or have a previous full dilatation caesarean section birth (p = 0.024). Infants born prior to 37 weeks were more likely to have a lower median birthweight (2270 vs 3300 g, p < 0.001), be admitted to a neonatal intensive care unit (53.8 % vs 2.3 %, p < 0.001) or experience short-term morbidity, including respiratory support (38.0 % vs 1.6 %, p < 0.001). ConclusionsOver 80% of women deemed to be at high risk of PTB gave birth at term gestations following attendance at a PSC during pregnancy. Most women can be successfully managed without interventions, instead employing a policy of serial cervical surveillance, to identify those at greatest risk of PTB.

Biomarkers associated with cardiovascular disease in women with spontaneous preterm birth: A case-control study.

Women with spontaneous preterm birth have an increased risk of cardiovascular disease later in life. Studies suggest potential pathophysiological mechanisms in common, but whether these could be identified by measurement of soluble circulating protein biomarkers in women with spontaneous preterm birth is unknown. The aim of this study was to determine if protein biomarkers associated with cardiovascular disease distinguish women with spontaneous preterm birth from healthy controls, both at pregnancy and at follow up. Study participants were identified in the population-based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid-pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow-up visit 4-15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up. gov registration NCT05693285. In the screening phase, fibrinogen, cadherin-5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D-binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow-up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up. Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid-pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease.

Anovaginal Colonization by Group B Streptococcus and Streptococcus anginosus among Pregnant Women in Brazil and Its Association with Clinical Features.

Streptococcus agalactiae (Group B Streptococcus; GBS) is a leading cause of neonatal invasive disease worldwide. GBS can colonize the human gastrointestinal and genitourinary tracts, and the anovaginal colonization of pregnant women is the main source for neonatal infection. Streptococcus anginosus, in turn, can colonize the human upper respiratory, gastrointestinal, and genitourinary tracts but has rarely been observed causing disease. However, in the last years, S. anginosus has been increasingly associated with human infections, mainly in the bloodstream and gastrointestinal and genitourinary tracts. Although anovaginal screening for GBS is common during pregnancy, data regarding the anovaginal colonization of pregnant women by S. anginosus are still scarce. Here, we show that during the assessment of anovaginal GBS colonization rates among pregnant women living in Rio de Janeiro, Brazil, S. anginosus was also commonly detected, and S. anginosus isolates presented a similar colony morphology and color pattern to GBS in chromogenic media. GBS was detected in 48 (12%) while S. anginosus was detected in 17 (4.3%) of the 399 anovaginal samples analyzed. The use of antibiotics during pregnancy and history of urinary tract infections and sexually transmitted infections were associated with the presence of S. anginosus. In turn, previous preterm birth was associated with the presence of GBS (p < 0.05). The correlation of GBS and S. anginosus with relevant clinical features of pregnant women in Rio de Janeiro, Brazil, highlights the need for the further investigation of these important bacteria in relation to this special population.

Validating the ratio of insulin like growth factor binding protein 4 to sex hormone binding globulin as a prognostic predictor of preterm birth in Viet Nam: a case-cohort study

Objective To validate a serum biomarker developed in the USA for preterm birth (PTB) risk stratification in Viet Nam. Methods Women with singleton pregnancies (n = 5000) were recruited between 19+0-23+6 weeks’ gestation at Tu Du Hospital, Ho Chi Minh City. Maternal serum was collected from 19+0-22+6 weeks’ gestation and participants followed to neonatal discharge. Relative insulin-like growth factor binding protein 4 (IGFBP4) and sex hormone binding globulin (SHBG) abundances were measured by mass spectrometry and their ratio compared between PTB cases and term controls. Discrimination (area under the receiver operating characteristic curve, AUC) and calibration for PTB <37 and <34 weeks’ gestation were tested, with model tuning using clinical factors. Measured outcomes included all PTBs (any birth ≤37 weeks’ gestation) and spontaneous PTBs (birth ≤37 weeks’ gestation with clinical signs of initiation of parturition). Results Complete data were available for 4984 (99.7%) individuals. The cohort PTB rate was 6.7% (n = 335). We observed an inverse association between the IGFBP4/SHBG ratio and gestational age at birth (p = 0.017; AUC 0.60 [95% CI, 0.53-0.68]). Including previous PTB (for multiparous women) or prior miscarriage (for primiparous women) improved performance (AUC 0.65 and 0.70, respectively, for PTB <37 and <34 weeks’ gestation). Optimal performance (AUC 0.74) was seen within 19-20 weeks’ gestation, for BMI >21 kg/m2 and age 20-35 years. Conclusion We have validated a novel serum biomarker for PTB risk stratification in a very different setting to the original study. Further research is required to determine appropriate ratio thresholds based on the prevalence of risk factors and the availability of resources and preventative therapies.

Comparative analysis of obstetric, perinatal, and neurodevelopmental outcomes following chorionic villus sampling and amniocentesis.

The risks of invasive prenatal tests are reported in previous studies such as miscarriage, fetal anomalies, and bleeding. However, few compare short-term and long-term outcomes between invasive tests. This study aims to investigate obstetric, perinatal, and children's neurodevelopmental outcomes following chorionic villus sampling (CVS) or amniocentesis in singleton pregnancy. This retrospective cohort study included healthy singleton pregnancies underwent transabdominal CVS (gestational age [GA] at 10-13 weeks) or amniocentesis (GA at 15-21 weeks) at a single medical center between 2012 and 2022. Only cases with normal genetic results were eligible. Short-term and long-term neurodevelopmental outcomes were evaluated. The study included 200 CVS cases and 498 amniocentesis cases. No significant differences were found in body mass index, parities, previous preterm birth, conception method, and cervical length (CL) before an invasive test between the groups. Rates of preterm labor, preterm premature rupture of the membranes, preterm birth, neonatal survival, neonatal short-term morbidities, and long-term neurodevelopmental delay were similar. However, the CVS group had a higher rate of cervical cerclage due to short CL before 24 weeks (7.0%) compared to the amniocentesis group (2.4%). CVS markedly increased the risk of cervical cerclage due to short CL (adjusted odd ratio [aOR] = 3.17, 95%CI [1.23-8.12], p = 0.016), after considering maternal characteristics. Performing CVS resulted in a higher incidence of cerclage due to short cervix or cervical dilatation compared to amniocentesis in singleton pregnancies. This highlights the importance of cautious selection for CVS and the necessity of informing women about the associated risks beforehand.

A new screening of preterm birth in gestation with short cervix after pessary plus progesterone.

This study aims to create a new screening for preterm birth < 34 weeks after gestation with a cervical length (CL) ≤ 30 mm, based on clinical, demographic, and sonographic characteristics. This is a post hoc analysis of a randomized clinical trial (RCT), which included pregnancies, in middle-gestation, screened with transvaginal ultrasound. After observing inclusion criteria, the patient was invited to compare pessary plus progesterone (PP) versus progesterone only (P) (1:1). The objective was to determine which variables were associated with severe preterm birth using logistic regression (LR). The area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were calculated for both groups after applying LR, with a false positive rate (FPR) set at 10%. The RCT included 936 patients, 475 in PP and 461 in P. The LR selected: ethnics white, absence of previous curettage, previous preterm birth, singleton gestation, precocious identification of short cervix, CL < 14.7 mm, CL in curve > 21.0 mm. The AUC (CI95%), sensitivity, specificity, PPV, and PNV, with 10% of FPR, were respectively 0.978 (0.961-0.995), 83.4%, 98.1%, 83.4% and 98.1% for PP < 34 weeks; and 0.765 (0.665-0.864), 38.7%, 92.1%, 26.1% and 95.4%, for P < 28 weeks. Logistic regression can be effective to screen preterm birth < 34 weeks in patients in the PP Group and all pregnancies with CL ≤ 30 mm.

Predicting preterm birth using explainable machine learning in a prospective cohort of nulliparous and multiparous pregnant women.

Preterm birth (PTB) presents a complex challenge in pregnancy, often leading to significant perinatal and long-term morbidities. "While machine learning (ML) algorithms have shown promise in PTB prediction, the lack of interpretability in existing models hinders their clinical utility. This study aimed to predict PTB in a pregnant population using ML models, identify the key risk factors associated with PTB through the SHapley Additive exPlanations (SHAP) algorithm, and provide comprehensive explanations for these predictions to assist clinicians in providing appropriate care. This study analyzed a dataset of 3509 pregnant women in the United Arab Emirates and selected 35 risk factors associated with PTB based on the existing medical and artificial intelligence literature. Six ML algorithms were tested, wherein the XGBoost model exhibited the best performance, with an area under the operator receiving curves of 0.735 and 0.723 for parous and nulliparous women, respectively. The SHAP feature attribution framework was employed to identify the most significant risk factors linked to PTB. Additionally, individual patient analysis was performed using the SHAP and the local interpretable model-agnostic explanation algorithms (LIME). The overall incidence of PTB was 11.23% (11 and 12.1% in parous and nulliparous women, respectively). The main risk factors associated with PTB in parous women are previous PTB, previous cesarean section, preeclampsia during pregnancy, and maternal age. In nulliparous women, body mass index at delivery, maternal age, and the presence of amniotic infection were the most relevant risk factors. The trained ML prediction model developed in this study holds promise as a valuable screening tool for predicting PTB within this specific population. Furthermore, SHAP and LIME analyses can assist clinicians in understanding the individualized impact of each risk factor on their patients and provide appropriate care to reduce morbidity and mortality related to PTB.

Feasibility of a pregnancy intervention mimicking viral transmission mitigation measures on the incidence of preterm birth in high-risk pregnant women enrolled in antenatal clinics in Melbourne, Australia: protocol for a pilot, randomised trial

IntroductionPreterm birth is a leading cause of perinatal morbidity and mortality. During the COVID-19 pandemic, reduction in rates of preterm birth in women exposed to viral mitigation measures was reported...

A prospective study of antepartum anxiety screening in patients with and without a history of spontaneous preterm birth

Maternal stress has been identified as one of the most common clinical phenotypes associated with preterm birth. The American College of Obstetricians and Gynecologists recommends anxiety screening at least once in the perinatal period. The prevalence of perinatal anxiety is challenged by the absence of formalized screening protocols and underreporting in high-risk populations, such as those with a history of adverse pregnancy outcomes. This study administered a validated anxiety screening tool in a cohort of patients with and without a previous spontaneous preterm birth and compared differences in score and rate of a positive screen between groups. Moreover, this study evaluated perinatal outcomes associated with a positive screen and described a referral protocol involving evaluation by a perinatal mental health counselor and clinical diagnoses. A hypothesis was made that patients with a previous history of spontaneous preterm birth would have higher self-reported anxiety symptoms than controls and that those with recurrent preterm delivery at <35 weeks of gestation would have the highest anxiety screening scores. This was a prospective observational cohort study administering the Generalized Anxiety Disorder 7-item screen to patients enrolled in 2 prenatal care clinics at our institution. The preterm birth cohort consisted of patients with a history of spontaneous preterm labor, premature rupture of membranes, or cervical insufficiency compared with the control cohort without this history. Screening was initiated at entry to prenatal care or referral to our high-risk obstetrical clinic. The inclusion criteria included English- or Spanish-speaking patients and singleton pregnancy, and the exclusion criteria included pregnancies complicated by a major congenital anomaly, enrollment after 34 weeks of gestation, delivery at <20 weeks of gestation, and incomplete delivery data. Referral to a mental health counselor was offered to those with a Generalized Anxiety Disorder 7-item screen score of ≥10. Perinatal outcomes as a comparison between the Generalized Anxiety Disorder 7-item screen-positive group and Generalized Anxiety Disorder 7-item screen-negative group were performed with statistical methods, including the Student t test, chi-square test, and Wilcoxon rank-sum test, with a P value of <.05 to determine significance. Between September 2020 and December 2021, 1349 participants were analyzed, with 143 patients (11%) in the previous preterm birth cohort and 1206 (89%) patients in the control cohort. Patients with a history of preterm birth and subsequent delivery at ≤35 weeks of gestation in the study pregnancy had significantly higher Generalized Anxiety Disorder 7-item screen scores than controls with delivery after 35 weeks of gestation (median score: 4 [interquartile range, 1-9] vs 2 [interquartile range, 0-6], respectively; P=.006). Overall, 187 participants (14%) screened positive with significantly higher rates in the previous preterm birth group than in the control group (20% vs 13%; P=.036). Of note, 117 patients (63%) accepted a referral, and 32 patients (17%) with a positive screen were diagnosed with a perinatal mood disorder. Patients with recurrent preterm birth have higher self-reported anxiety using the Generalized Anxiety Disorder 7-item screen than controls. Of those with a positive screen, 17% were diagnosed with a perinatal mood disorder.

“I had given up on being a mother”: a survey of 183 women’s experience of transabdominal cerclage (TAC)

BackgroundTransabdominal cerclage (TAC) is a relatively uncommon intervention for preventing preterm birth. This study aimed to investigate the experience of women who had undergone this procedure.MethodsThe survey was designed in collaboration with a preterm birth studies public and patient involvement (PPI) group and ethical approval was granted by KCL BDM Research Ethics Panel (LRS-19/20-13205). Members of closed Facebook group, UK TAC Support, were invited to complete an online questionnaire about their experience of TAC, and pregnancies before and after having it placed. The survey was open between December 2019 and May 2020. Open and closed questions provided both qualitative and quantitative data for analysis, which was carried out using NVivo Pro 2020 v.1.4.1 qualitative data management software and SPSS Statistics 27 (IBM).ResultsOne hundred eighty-three participants completed the survey, having had TAC procedures carried out in 36 hospitals. Altogether, participants had experienced 287 preterm births (PTB) and late miscarriages (LM), equating to an average of 1.6 each (range 0–5), including 18 stillbirths. TAC was indicated in 123 (67%) for previous PTB and/or LM, 29 (16%) for cervical surgery and 31 (17%) for both. 151 (83%) TAC procedures were open, 32 (17%) laparoscopic. 86% (n = 157) were placed outside pregnancy. Of those placed in pregnancy, gestation at TAC ranged from 7 to 16 weeks. When comparing earliest pre- and post-TAC pregnancy gestation (excluding first trimester losses), median gestational weeks gained following TAC was 15.5 weeks (SD 6.89). Qualitative themes included: the struggle to get treatment; lack of TAC knowledge amongst clinicians; gratitude, hope and feeling protected; possible detrimental effects of TAC.ConclusionsThis very high-risk group found having a TAC gave great reassurance and hope, and were very grateful to have found the care they needed. However, they often struggled to get this support, frequently due to lack of clinician awareness. This may improve following roll-out of NHS England’s Saving Babies Live Care Bundle and NHS commissioning guidelines for care of women at risk of PTB.

EP02.35: Pessary plus progesterone to prevent preterm birth in women with previous spontaneous preterm birth and short cervix in a low‐income country

EP02.35: Pessary plus progesterone to prevent preterm birth in women with previous spontaneous preterm birth and short cervix in a low‐income country

Prediction of spontaneous preterm birth using CCL2 and CXCL10 in maternal serum of symptomatic high-risk pregnant women: a prospective cohort study

IntroductionCCL2 and CXCL10 are putative biomarkers for the prediction of spontaneous preterm birth. This study evaluates these markers in a cohort of pregnant high-risk women.Material and methodsIn our prospective study, we included 109 women with signs of preterm labor between 20 + 0 and 31 + 6 weeks of gestation. Inclusion criteria were regular (< 3/30 min) or painful contractions, cervical length < 25 mm or a history of previous preterm birth (PTB). Blood samples were obtained upon first admission to our clinic. Biomarker concentrations were measured using pre-coated sandwich immunoassays (ELISA). Primary study outcome was spontaneous preterm birth < 34 weeks, secondary outcome was delivery < 37 weeks or within seven days after study inclusion.ResultsSixteen women (14.7%) delivered < 34 weeks and twenty women between 34 + 0 and 36 + 6 weeks (18.4%). Six patients (5.5%) gave birth within seven days after study admission. CXCL10 showed higher medium serum levels in women with PTB < 34 weeks (115 pg/ml compared to 61 pg/ml ≥ 34 weeks; p < 0.001) and < 37 weeks (103 pg/ml vs. 53 pg/ml; p < 0.001). In contrary, lower CCL2 serum levels were associated with PTB < 34 weeks (46 pg/ml vs. 73 pg/ml; p = 0.032) and birth within 7 days (25 pg/ml vs. 73 pg/ml; p = 0.008). The CXCL10/CCL2-ratio further improved the predictive model with a ROC-AUC of 0.83 (95% CI 0.73–0.93, p < 0.001) for delivery < 34 weeks. These corresponds to a sensitivity, specificity and positive predictive value of 0.67, 0.86 and 0.43 at a cut-off of 2.2.ConclusionLow maternal serum CCL2 levels are associated with a higher risk of preterm delivery within seven days. High CXCL10 serum levels are more associated with a high risk for preterm birth < 34 weeks. Elevated CXCL10/CCL2-ratio is showing the best predictive performance.Trial registration number (DRKS-ID)DRKS00010763, Registration date: September 02, 2016.

Role Of Low Dose Aspirin In Preventing Preterm Birth In Patients With Previous History Of Preterm Delivery

Objective: Preterm birth (PTB) occurs between 24-37 weeks of gestation. The important risk factor for PTB is a previous PTB and currently progesterone is used for the management of recurrent spontaneous PTB. Some studies have shown good outcomes but recent studies revealed that the use of vaginal progesterone was not related to a decreased likelihood of PTB or neonatal adverse effects. Thus, the controversy in the literature suggests multiple underlying pathological mechanisms involved in the progression of PTB. This study aims to determine the role of low-dose aspirin in the prevention of preterm birth in patients with a previous history of preterm delivery. Methodology: In this randomized controlled trial, a total of 172 patients fulfilling the inclusion criteria were selected from the inpatient and outpatient departments. Patients were divided randomly into two groups (group A and group B), using random number tables. In Group A, low-dose aspirin (75mg) was given while group B was taken as a control group. Patients were called every 8 weeks in the outpatient department for the assessment of compliance and side effects of the drug. The data were entered and analyzed by using SPSS v25.0. Chi-square was used to compare the two groups for incidence of preterm birth. Relative risk (along with a 95% confidence interval) for the decrease in the incidence of preterm birth with the use of aspirin was calculated. Results: The age of participants included in the study was 18 to 40 years. The mean age of patients in group A was 33.85±5.210 years and in group B was 32.86±4.139 years. The mean fetal birth weight in group A was 2281.1962±363.125 grams and in group B was 2271.4344±374.797 grams. In the low-dose aspirin group, 10(11.6%) had preterm birth and 31(36.0%) in the control group with a p-value of 0.001, which is statistically significant. The risk of having preterm birth with low-dose aspirin was 1.801 times less than controls. Conclusion: aspirin in low dose given before 14 weeks of gestation decrease spontaneous preterm birth as compared to the control group in a woman with a history of previous preterm birth which was spontaneous

A cross-sectional survey of women’s views and preferences for preterm birth screening and treatment

ObjectivesPrimary outcomes were to determine; 1) the desire for more patient information from healthcare professionals on preterm birth (PTB) prevention 2) the desire for PTB screening surveillance or participation in research or 3) the acceptability of transvaginal ultrasound (TVUS) or vaginal examinations to predict spontaneous PTB. MethodsA 19-question, piloted, self-administered survey was completed by unselected pregnant women in a tertiary maternity hospital in Dublin, Ireland. Data was collected to include maternal socio-demographics, past obstetric history, and current pregnancy details, in addition to views and preferences on PTB screening and preventative treatments. Statistical analysis to include binary and multinomial regression was performed by IBM SPSS Statistics for Windows (Version 29.0). Results277 women completed the study survey. 9.4% of women had attended the preterm birth surveillance clinic (PSC). 75.1% of respondents indicated a preference for more information from healthcare professionals about PTB. 65% reported that TVUS and vaginal examinations were acceptable in pregnancy. The acceptability of antenatal examinations was significantly influenced by ethnicity; white European (OR 2.58, CI 1.12–5.95, p = 0.003) and Asian (OR 3.39, CI 1.18–9.67, p = 0.02). Discomfort (25.3%) and vaginal bleeding (11.9%) were the most frequently reported concerns about TVUS. 95.7% of unselected women indicated that they would accept treatment to prevent PTB. Vaginal progesterone (53.8%) was preferred treatment compared to cervical cerclage (15.9%) or cervical pessary (16.6%).55.6% of respondents stated they attend or wish to attend for additional appointments or research opportunities for PTB screening. Women with a previous PTB or second trimester miscarriage were more likely to attend or wish to attend for PTB screening (OR 3.23, CI 1.34–7.79, p = 0.009). ConclusionPTB is an important healthcare priority for pregnant women in Ireland. However, women require more information, counselling and reassurance about the utility and safety of TVUS in PSCs.

Birth spacing and risk of adverse pregnancy and birth outcomes: A systematic review and dose-response meta-analysis.

The association between extreme birth spacing and adverse outcomes is controversial, and available evidence is fragmented into different classifications of birth spacing. We conducted a systematic review of observational studies to evaluate the association between birth spacing (i.e., interpregnancy interval and interoutcome interval) and adverse outcomes (i.e., pregnancy complications, adverse birth outcomes). Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using a random-effects model, and the dose-response relationships were evaluated using generalized least squares trend estimation. A total of 129 studies involving 46 874 843 pregnancies were included. In the general population, compared with an interpregnancy interval of 18-23 months, extreme intervals (<6 months and ≥ 60 months) were associated with an increased risk of adverse outcomes, including preterm birth, small for gestational age, low birthweight, fetal death, birth defects, early neonatal death, and premature rupture of fetal membranes (pooled OR range: 1.08-1.56; p < 0.05). The dose-response analyses further confirmed these J-shaped relationships (pnon-linear < 0.001-0.009). Long interpregnancy interval was only associated with an increased risk of preeclampsia and gestational diabetes (pnon-linear < 0.005 and pnon-linear < 0.001, respectively). Similar associations were observed between interoutcome interval and risk of low birthweight and preterm birth (pnon-linear < 0.001). Moreover, interoutcome interval of ≥60 months was associated with an increased risk of cesarean delivery (pooled OR 1.72, 95% CI 1.04-2.83). For pregnancies following preterm births, an interpregnancy interval of 9 months was not associated with an increased risk of preterm birth, according to dose-response analyses (pnon-linear = 0.008). Based on limited evidence, we did not observe significant associations between interpregnancy interval or interoutcome interval after pregnancy losses and risk of small for gestational age, fetal death, miscarriage, or preeclampsia (pooled OR range: 0.76-1.21; p > 0.05). Extreme birth spacing has extensive adverse effects on maternal and infant health. In the general population, interpregnancy interval of 18-23 months may be associated with potential benefits for both mothers and infants. For women with previous preterm birth, the optimal birth spacing may be 9 months.