High-risk Singleton Pregnancies Research Articles

Role of Cerebroplacental Ratio in Predicting Perinatal Outcome.

Objective Doppler velocimetry provides a sensitive, non-invasive, and safe method of surveillance of fetal hemodynamics and fetomaternal circulation. Cerebroplacental ratio (CPR) is an indicator of placental function and fetal maladaptation to placental insufficiency. Cerebroplacental ratio (CPR) is becoming a significant indicator of unfavorable pregnancy outcomes, which has implications for the assessment of fetal well-being. This study aimedto determine the cut-off value of the cerebroplacental ratio (CPR) in appropriate for gestational age (AGA) fetuses in high-risk mothers to predict adverse perinatal outcomes. We also compared the efficacy of CPR, umbilical artery pulsatility index (UmA PI), and middle cerebral artery pulsatility index (MCA PI) for predicting adverse perinatal outcomes. Design and setting This was a prospective observational study conducted at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Methods A total of 100 women with singleton high-risk pregnancies were included in this prospective observational study. Obstetric ultrasound was performed at the time of recruitment, and fetal weight and CPR were noted. Based on fetal weight, patients were divided into AGA and fetal growth restriction (FGR) groups; CPR was measured; patients were followed up fortnightly; and outcomes were noted. Main outcome The effectiveness of CPR, UmA PI, and MCA PI for predicting poor perinatal outcomes and identifying the cut-off value of CPR in appropriate for gestational age (AGA) fetuses in high-risk mothers was assessed. Result The values of MCA PI, UmA PI, and CPR were statistically significant between AGA and FGR (p-value =.023, .002 and .0001), respectively. The cut-off value for CPR-detecting adverse outcomes in AGA was 1.49. It has sensitivity, specificity, positive predictive value, and negative predictive value of 67.5%, 68%, 71.69%, and 70.21%, respectively. Conclusion Cerebroplacental ratio (CPR) reflects both circulatory insufficiency of the placenta and adaptive changes of the middle cerebral artery, indicating an important non-invasive surveillance modality.

Role of Shear Wave Elastography of Placenta in Prediction of Preeclampsia in High-Risk Pregnancy.

The aim of our study was to compare the placental elasticity values between normal pregnancies and preeclamptic pregnancies and evaluate the utility of shear-wave elastography of the placenta as a predictor for preeclampsia in high-risk pregnancy. A prospective study was performed with 90 singleton high-risk pregnancies having any of the 7 risk factors for developing preeclampsia (primigravida, history of preeclampsia, family history of preeclampsia, history of pregestational diabetes, chronic hypertension, advanced maternal age [≥40 years], and body mass index ≥26 kg/m 2 ) were enrolled in the study. Shear-wave elastography was performed in all patients at 20 to 24 weeks' gestation and at 34 to 36 weeks' gestation, at 2 sites: center and edge of the placenta. The patients were divided into 2 groups: normal pregnancies (group A) or developed preeclampsia (group B). Women with posterior placentation, obstetric disorders other than preeclampsia, or multiple gestation were excluded from the study. Group comparisons were done using the χ2 test or Fisher exact test. Shear-wave elasticity values at 20 to 24 weeks' gestation for group B at the center of the placenta (21.73 vs 9.72 kPa) and at the edge of the placenta (21.6 kPa vs 10.15 kPa) were significantly higher than those for group A ( P < 0.05). Similar results were seen at 34 to 36 weeks' gestation. With a cutoff of 13.1 kPa, we attained sensitivity of 95.2%, specificity of 92.8% and diagnostic accuracy of 93.3% for predicting development of preeclampsia. Patients with preeclampsia have a significantly higher stiffness of the placenta. Shear-wave elastography is useful to evaluate placental function. Elastography can be used as a supplementary tool for prediction of preeclampsia.

Abstract P201: First Trimester Anxiety Is Associated With Increased Arterial Stiffness In High-risk Pregnant Women

Preeclampsia is a leading pregnancy complication characterized by vascular dysfunction, leading to hypertension and organ damage. Evidence suggests positive associations between higher arterial stiffness and preeclampsia, as well as anxiety and preeclampsia. Anxiety, a transdiagnostic factor, is also associated with increased arterial stiffness in the general population, but no reports exist in pregnant women. Moreover, the association between anxiety and arterial stiffness in pregnancy and the risk of developing preeclampsia has not yet been explored. To address this gap, we aimed to evaluate the role of anxiety in arterial stiffness measurements and the development of preeclampsia in high-risk pregnant women. In this prospective study, women with high-risk singleton pregnancies before 14 weeks gestation were recruited at two tertiary care obstetric clinics in Montreal, Canada, and followed throughout pregnancy. Arterial stiffness parameters (carotid-femoral pulse wave velocity [cfPWV]) were measured at baseline (10-13 weeks gestation) and at four-week intervals throughout pregnancy. Self-reported anxiety symptoms were recorded using the Beck Anxiety Inventory, and participants’ scores were ranked as having minimal, mild, moderate, or severe anxiety. After excluding incomplete questionnaires, the total study sample comprised 156 women, of whom 10 (6.4%) developed preeclampsia. There was no difference in anxiety scores between groups based on baseline characteristics (i.e., age, BMI, and race). First trimester anxiety scores were associated with increased cfPWV in the early and late second trimester time points (p=0.02, p= 0.04, respectively). Higher baseline anxiety was also associated with a greater increase in cfPWV from baseline to 18 weeks gestation (p=0.04). A trend was also observed between baseline anxiety scores and the development of preeclampsia (p=0.07). Anxiety in the first trimester of pregnancy is associated with higher cfPWV values and a greater increase from the first to the second trimester, as well as potentially a higher risk for preeclampsia. Our ongoing study will further explore these findings as they can have important implications for patient prenatal care.

Trisomy 21 Testing in Second Trimester: Reliability Comparison of Triple and Quadruple Testing in Pakistan

Objectives: Down syndrome is a disorder that affects one in every 700 babies born, and it is one of the most frequent causes of developmental delay (DS). In Pakistan, prenatal screening for Down syndrome is not being practised according to any approved protocol. The biochemical screening that takes place during the second trimester is still carried out using the triple test. Although the quadruple test has a better sensitivity and specificity than other diagnostic methods, its usage in routine medical settings is not advised. The purpose of this study was to explore the second trimester screening for trisomy 21 (quadruple test with genetic sonogram) in order to determine its sensitivity and accuracy in comparison to biochemical testing. Place of Study: District Headquarters Hospital, Gujranwala Duration of Study: January 2021 to December 2021 Methods: This retrospective observational study was carried out in a Fetal Medicine Centre with the purpose of analysing the odds of being affected with Down syndrome, given a positive risk (OAPR) upon screening in the quadruple test; triple test and quadruple test plus a genetic sonogram for highrisk singleton pregnancies (in view of advanced maternal age; an anomaly scan showing some abnormality, etc.). Given the presence of a positive risk factor, the goal of this study was to ascertain the likelihood of having a child impacted by Down syndrome. Practical Implication: To explore the second trimester screening for trisomy 21 (quadruple test with genetic sonogram) in order to determine its sensitivity and accuracy in comparison to biochemical testing. Results: The discovery of trisomies was made after an investigation into 3,042 highrisk pregnancies with a singleton baby. 327 pregnant women who have received positive findings from a triple test, quadruple test, or quadruple test in addition to a genetic ultrasonography opt to have an amniocentesis. This decision was made after the ladies learned that their unborn child may have a genetic disorder. It was discovered that 20 of the developing babies were affected by Down syndrome. The OAPR for the quadruple test was demonstrated to be significantly higher when compared to the OAPR for the triple test (1:29.1 as compared to 1:39.2). It was found that the combination of the triple test and the genetic sonogram had the highest OAPR of 1:7. Conclusions: The triple test combined with a genetic sonogram is the most effective tool for screening for trisomy 21, and it has the potential to cut down on the number of unnecessary amniocentesis operations carried out in high-risk populations. Keywords: Down syndrome, genetic, quadruples test, second trimester screening, triple test,ultrasound

Obstetric Indications for Progestin Therapy

Specifically, meta-analyses of randomized trials demonstrate that vaginal progesterone reduces the risk of preterm birth in selected high-risk singleton pregnancies. 17-OHPC may also reduce the risk of recurrent preterm birth in singletons. Finally, one trial suggests that vaginal progesterone may also be beneficial in improving live birth rates in singletons with prior miscarriages and early pregnancy bleeding.

Performance of a cfDNA prenatal screening test, choice of prenatal procedure, and chromosome conditions identified during pregnancy after low-risk cfDNA screening.

To evaluate the performance of cell-free DNA (cfDNA) screening for common fetal aneuploidies, choice of prenatal procedure, and chromosome conditions identified during pregnancy after low-risk cfDNA screening. A single-centre prenatal cfDNA screening test was employed to detect trisomies 21, 18 and 13 (T21, T18, T13) and sex chromosome aneuploidies (SCAs). Test performance, choice of prenatal procedure, and cytogenetic results in pregnancies with low-risk cfDNA screening were reviewed. CfDNA screening of 38,289 consecutive samples identified 720 (1.9%) pregnancies at increased risk for aneuploidy. Positive predictive values (PPVs) for high-risk singleton pregnancies were 98.5% (T21), 92.5% (T18) and 55.2% (T13). PPVs for SCAs ranged from 30.6-95.2%. Most women elected chorionic villus sampling for prenatal diagnosis of T21, T18 and T13; amniocentesis and/or postnatal testing were commonly chosen for SCAs. Cytogenetic tests from 616 screen-negative pregnancies identified 64 cases (12.7%) with chromosome conditions not detected by cfDNA screening, including triploidy (n=30) and pathogenic and likely pathogenic copy number variants (n=34). Fifteen (0.04%) false-negative common aneuploidy results were identified. CfDNA screening was highly accurate for detecting fetal aneuploidy in this general-risk obstetric population. Fetal ultrasound and prenatal diagnostic testing were important in identifying chromosome conditions in pregnancies screened as low-risk. This article is protected by copyright. All rights reserved.

S-11-1: ARTERIAL STIFFNESS AND HEMODYNAMIC PARAMETERS FOR THE EARLY PREDICTION OF PREECLAMPSIA: A PROSPECTIVE COHORT STUDY

Objective: Preeclampsia is a leading complication of pregnancy, yet there remains no reliable clinical tool for its early prediction. Assessment of vascular dysfunction, a central feature of preeclampsia, by arterial stiffness and hemodynamic measurements could be a promising tool for preeclampsia prediction. This study aimed to evaluate 1) arterial stiffness and hemodynamic parameters as an early predictive tool for preeclampsia, and 2) longitudinal changes in these parameters and identify changepoints prior to preeclampsia onset. Design and method: In this prospective longitudinal cohort study of women with singleton high-risk pregnancies (n = 236), arterial stiffness (carotid-femoral pulse wave velocity, cfPWV) and wave reflection (augmentation index [AIx], and time to wave reflection [T1R]) were assessed using applanation tonometry (SphygmoCor, AtCor) at 10–13 weeks and repeated every 4 weeks throughout pregnancy. Circulating angiogenic biomarkers (soluble fms-like tyrosine kinase, and placental growth factor) were measured (Quantikine, R&amp;D Systems) at each trimester, and a bilateral uterine artery Doppler (UAD) was performed in the second trimester. The predictive ability of arterial stiffness was compared to that of peripheral blood pressure, UAD indices, as well as angiogenic biomarkers. Furthermore, changepoints in cfPWV, AIx, and T1R were compared between women who did and did not subsequently develop preeclampsia. Results: A first-trimester 1 m/s increase in cfPWV was associated with 64% increased odds (p &lt; 0.05), while a 1 ms increase in T1R with 11% decreased odds for preeclampsia (p &lt; 0.01). The area under the curve of arterial stiffness, blood pressure, ultrasound indices, and angiogenic biomarkers was 0.84, 0.68, 0.66, and 0.64, respectively (Figure). A changepoint in cfPWV was detected at 14–17 weeks. cfPWV then increased in women who subsequently developed preeclampsia but decreased in women who did not; a 1.2 m/s difference in cfPWV between the groups was observed at 22–25 weeks. An increase in AIx was noted at 18–21 weeks while at 30–33 weeks in women who did and did not develop preeclampsia, respectively. Conclusions: Arterial stiffness and wave reflection were higher in the first trimester and throughout pregnancy in women destined to develop preeclampsia. These indices predicted preeclampsia earlier (in the first trimester) and with greater ability than blood pressure, UAD, and/or angiogenic biomarkers. Furthermore, altered vascular adaptations in the early second trimester were observed in women who subsequently developed preeclampsia. These findings demonstrate the potential clinical utility of arterial stiffness and hemodynamic parameters as an early screening tool for preeclampsia, which can be used to inform clinical management of high-risk pregnancies.

Prenatal Diagnosis Using Chromosomal Microarray Analysis in High-Risk Pregnancies.

Background: To assess the value of chromosomal microarray analysis (CMA) during the prenatal diagnosis of high-risk pregnancies. Methods: Between January 2016 and November 2021, we included 178 chorionic villi and 859 amniocentesis samples from consecutive cases at a multiple tertiary hospital. Each of these high-risk singleton pregnancies had at least one of the following indications: (1) advanced maternal age (AMA; ≥35 years; 546, 52.7%); (2) fetal structural abnormality on ultrasound (197, 19.0%); (3) high-risk first- or second-trimester Down syndrome screen (189, 18.2%), including increased nuchal translucency (≥3.5 mm; 90, 8.7%); or (4) previous pregnancy, child, or family history (105, 10.1%) affected by chromosomal abnormality or genetic disorder. Both G-banding karyotype analysis and CMA were performed. DNA was extracted directly and examined with oligonucleotide array-based comparative genomic hybridization. Results: Aneuploidies were detected by both G-banding karyotyping and CMA in 42/1037 (4.05%) cases. Among the 979 cases with normal karyotypes, 110 (10.6%) cases had copy number variants (CNVs) in CMA, including 30 (2.9%) cases with reported pathogenic and likely pathogenic CNVs ≥ 400 kb, 37 (3.6%) with nonreported VOUS, benign, or likely benign CNVs ≥ 400 kb, and 43 (4.1%) with nonreported CNVs < 400 kb. Of the 58 (5.6%) cases with aneuploidy rearrangements, 42 (4.1%) were diagnosed by both G-banding karyotyping and CMA; four inversions, six balanced translocations, and six low mosaic rates were not detected with CMA. Conclusions: CMA is an effective first step for the prenatal diagnosis of high-risk pregnancies with fetal structural anomalies found in ultrasonography or upon positive findings.

Abnormal vaginal flora and spontaneous preterm birth in high-risk singleton pregnancies with cervical cerclage

Objective To investigate abnormal vaginal and suture-based bacterial flora for associations with spontaneous preterm birth in high-risk singleton pregnancies with an ultrasound-indicated or emergency cervical cerclage. Materials and methods A retrospective study of 196 singleton pregnancies with an ultrasound-indicated or emergency cerclage at the Royal Women’s Hospital, Australia, from 2004 to 2018. High vaginal swabs were collected regularly between 14 and 26 weeks’ gestation, including pre- and post-cerclage insertion, and sent for microscopy and culture. Cervical suture was cultured upon removal. Primary outcomes were spontaneous preterm birth <37, <34 and <30 weeks. Results 43.4% (85/196) of women delivered preterm. The acquisition and persistence of vaginal Escherichia coli following cerclage insertion were independently associated with spontaneous preterm birth <37 weeks (p = .0225, p = .0477). Escherichia coli growth from the cervical suture upon removal was associated with spontaneous preterm birth <34 weeks (p = .0458). The acquisition of vaginal mixed anaerobes post-cerclage was independently associated with spontaneous preterm birth <34 weeks (p = .0480) Conclusion For singleton pregnancies with an ultrasound-indicated or emergency cerclage, the presence of vaginal or suture-based Escherichia coli following cerclage insertion yields increased risk of cerclage failure and spontaneous preterm birth.

311 Predictive ability of cerebroplacental ratio for adverse perinatal outcome in the third trimester

Introduction and aims: Fetal growth restriction is associated with increased risk of adverse perinatal outcome. The aim was to investigate the potential of cerebroplacental ratio (CPR) to predict adverse perinatal outcome in high-risk pregnancies in the third trimester. Another aim was to study if CPR has better predictive value than its components, middle cerebral artery (MCA) pulsatility index (PI) and umbilical artery (UA) PI. Methods: A register-based study including 1573 singleton high-risk pregnancies with Doppler examinations at 32+0 to 40+6 gestational weeks at two perinatal centers between 1994 and 2017.

Sleep-disordered breathing in high-risk pregnancies is associated with elevated arterial stiffness and increased risk for preeclampsia

Impaired vascular function is a central feature of pathologic processes preceding the onset of preeclampsia. Arterial stiffness, a composite indicator of vascular health and an important vascular biomarker, has been found to be increased throughout pregnancy in those who develop preeclampsia and at the time of preeclampsia diagnosis. Although sleep-disordered breathing in pregnancy has been associated with increased risk for preeclampsia, it is unknown if sleep-disordered breathing is associated with elevated arterial stiffness in pregnancy. This prospective observational cohort study aimed to evaluate arterial stiffness in pregnant women, with and without sleep-disordered breathing and assess the interaction between arterial stiffness, sleep-disordered breathing, and preeclampsia risk. Women with high-risk singleton pregnancies were enrolled at 10 to 13 weeks' gestation and completed the Epworth Sleepiness Score, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaires at each trimester. Sleep-disordered breathing was defined as loud snoring or witnessed apneas (≥3 times per week). Central arterial stiffness (carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness), peripheral arterial stiffness (carotid-radial pulse wave velocity), wave reflection (augmentation index, time to wave reflection), and hemodynamics (central blood pressures, pulse pressure amplification) were assessed noninvasively using applanation tonometry at recruitment and every 4 weeks from recruitment until delivery. High-risk pregnant women (n=181) were included in the study. Women with sleep-disordered breathing (n=41; 23%) had increased carotid-femoral pulse wave velocity throughout gestation independent of blood pressure and body mass index (P=.042). Differences observed in other vascular measures were not maintained after adjustment for confounders. Excessive daytime sleepiness, defined by Epworth Sleepiness Score >10, was associated with increased carotid-femoral pulse wave velocity only in women with sleep-disordered breathing (Pinteraction=.001). Midgestation (first or second trimester) sleep-disordered breathing was associated with an odds ratio of 3.4 (0.9-12.9) for preeclampsia, which increased to 5.7 (1.1-26.0) in women with sleep-disordered breathing and hypersomnolence, whereas late (third-trimester) sleep-disordered breathing was associated with an odds ratio of 8.2 (1.5-39.5) for preeclampsia. High-risk pregnant women with midgestational sleep-disordered breathing had greater arterial stiffness throughout gestation than those without. Sleep-disordered breathing at any time during pregnancy was also associated with increased preeclampsia risk, and this effect was amplified by hypersomnolence.

Utility of the cerebroplacental ratio (CPR) in marijuana exposed growth restricted fetuses

Objective Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcomes. The cerebroplacental ratio (CPR) represents the interaction of alterations in blood flow to the fetal brain and placenta. CPR has been utilized as a superior reflection of fetal hypoxia/acidemia and therefore a better predictor of fetal morbidity. We sought to determine the role of the CPR as an adjunctive tool to identify fetuses at increased risk of adverse perinatal outcomes in a study population of marijuana (MJ) exposed FGR fetuses. Methods This was a retrospective cohort study of high-risk singleton pregnancies over a 4-year period. Self-identified daily MJ users with FGR fetuses in the 3rd trimester were isolated. Fetal biometry, amniotic fluid indices, and CPRs were calculated. A CPR <1 was considered abnormal. FGR fetuses with normal and abnormal CPRs were then compared. Results 26/192 (13.5%) of MJ exposed fetuses were diagnosed with FGR in the 3rd trimester. 12/26 (46%) had an abnormal CPR and 14 had a normal CPR (mean CPR 0.60 vs 1.57, p = .0001). The mean EFW percentile was lower in the abnormal CPR group in comparison to the group with normal CPR (3.33 vs 7.64, p = .0001). Both groups showed evidence of brain sparing with an overall mean head circumference of 17.55 in comparison to a mean abdominal circumference of 5.63. A CPR <1 was associated with more severe FGR, oligohydramnios, and abnormal UA Doppler studies. Conclusions Approximately half of the MJ exposed FGR fetuses had an abnormal CPR. In this subset of patients, >90% had severe FGR, a higher proportion had absence/reversal of end diastolic flow in the UA, and a higher proportion had oligohydramnios. This demonstrates that an abnormal CPR identifies a group of FGR fetuses at a greater risk of adverse perinatal outcomes.

Mediterranean diet, Mindfulness-Based Stress Reduction and usual care during pregnancy for reducing fetal growth restriction and adverse perinatal outcomes: IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa): a study protocol for a randomized controlled trial

BackgroundFetal growth restriction (FGR) affects 7–10% of all pregnancies resulting in a higher risk of perinatal morbidity and mortality, long-term disabilities, and cognitive impairment. Due to its multifactorial etiology, changes in maternal lifestyle, including suboptimal maternal diet and stress, have increasingly been associated with its prevalence. We present a protocol for the Improving Mothers for a better PrenAtal Care Trial Barcelona (IMPACT BCN), which evaluates two different maternal lifestyle strategies (improved nutrition by promoting Mediterranean diet and stress reduction program based on mindfulness techniques) on perinatal outcomes. The primary objective is to reduce the prevalence of FGR. Secondary aims are to reduce adverse perinatal outcomes and to improve neurodevelopment and cardiovascular profile in children at 2 years of age.MethodsA randomized parallel, open-blind, single-center trial following a 1:1:1 ratio will select and randomize high-risk singleton pregnancies for FGR (N=1218), according to the criteria of the Royal College of Obstetricians and Gynaecologists (19.0–23.6 weeks’ gestation), into three arms: Mediterranean diet, mindfulness-based stress reduction program, and usual care without any intervention. Compliance to the interventions will be randomly tested in 30% of participants with specific biomarkers. Maternal socio-demographic, clinical data, biological samples, and lifestyle questionnaires will be collected at enrollment and at the end of the interventions (34.0–36.6 weeks’ gestation), together with a fetoplacental ultrasound and magnetic resonance. Fetoplacental biological samples and perinatal outcomes will be recorded at delivery. Postnatal follow-up is planned up to 2 years of corrected age including neurodevelopmental tests and cardiovascular assessment. Intention-to-treat and population per-protocol analysis will be performed.DiscussionThis is the first randomized study evaluating the impact of maternal lifestyle interventions during pregnancy on perinatal outcomes. The maternal lifestyle interventions (Mediterranean diet and mindfulness-based stress reduction program) are supported by scientific evidence, and their compliance will be evaluated with several biomarkers.Trial registrationClinicalTrials.govNCT03166332. Registered on April 19, 2017

Vaginal progesterone for prevention of preterm birth in asymptomatic high-risk women with a normal cervical length: a systematic review and meta-analysis protocol

BackgroundPreterm birth (PTB) is estimated to affect 14.9 million babies globally every year. Global rates of PTB continue to increase from 9.8 to 10.6% over a 15-year period from 2000 to 2014. Vaginal progesterone is commonly used by clinicians as a prevention strategy, with recent evidence affirming the benefit of vaginal (micronised) progesterone to prevent PTB in women with a shortened cervix (< 25 mm). Given the low incidence of a short cervix at mid-gestation in high-risk populations further evidence is required. The objective of this review is to determine if vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy with a normal mid-gestation cervical length.MethodsStudies will be sourced from MEDLINE, Embase and Cochrane Register of Trials (CENTRAL) from their inception onwards with the search terms ‘progesterone’ and ‘preterm birth’. Studies will be screened and included if they assess vaginal progesterone compared to placebo in women with a normal cervical length. The primary outcome will be sPTB < 37 weeks, with secondary outcomes of sPTB < 34 weeks.Two independent reviewers will conduct study screening at abstract and full text level, data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. The Mantel-Haenszel statistical method and random effects analysis model will be used to produce treatment effect odds ratios and corresponding 95% confidence intervals.DiscussionThis review will assess the current body of evidence and provide clarity regarding the potential benefits and best practice of use of vaginal progesterone in asymptomatic women with high-risk singleton pregnancies and normal cervical length.Trial registrationPROSPERO CRD42020152051

The contemporary value of dedicated preterm birth clinics for high-risk singleton pregnancies: 15-year outcomes from a leading maternal centre.

Preterm birth clinics provide dedicated obstetric care to women athigh risk of spontaneous preterm birth (SPTB). There remains a lack of conclusive evidence to support the overall utility of such clinics, attributable to a paucity and heterogeneity of primary data. This study audits Australia's largest and oldest dedicated preterm birth clinic with the aim to add primary data to the area and offer opportunities for similar clinics to align practice. A retrospective audit of referrals to the Preterm Labour Clinic at the Royal Women's Hospital, Melbourne, Australia, between 2004 and 2018 was conducted. 1,405 singleton pregnancies met inclusion criteria. The clinic's key outcomes, demographics, predictive tests and interventions were analysed. The primary outcomes were SPTB before 37, 34 and 30weeks' gestation. The overall incidence of SPTB in the clinic was 21.2% (n=294). Linear regression showed reductions in the adjusted rates of overall SPTB and pre-viable SPTB (delivery <24weeks) from 2004 (108%; 8%) to 2018 (65%; 2% respectively). Neonatal morbidity and post-delivery intensive care admission concurrently declined (p=0.02; 0.006 respectively). Rates of short cervix (cervical length <25mm) increased over time (2018: 30.9%) with greater uptake of vaginal progesterone for treatment. Fetal fibronectin, mid-trimester short cervix, and serum alkaline phosphatase were associated with SPTB on logistic regression. Dedicated preterm birth clinics can reduce rates of SPTB, particularly deliveries before 24weeks' gestation, and improve short-term neonatal outcomes in pregnant women at risk of preterm birth.

A longitudinal analysis of arterial stiffness and wave reflection in preeclampsia: Identification of changepoints

PurposePreeclampsia (PrE) is a leading complication of pregnancy characterized by vascular dysfunction. Characterizing the longitudinal changes in vascular function prior to PrE onset is critical to the identification of optimal timepoints for vascular assessment and the development of effective early screening strategies. MethodsIn this prospective longitudinal study of women with singleton high-risk pregnancies, arterial stiffness and wave reflection parameters were assessed using applanation tonometry at 10–13 weeks' gestation and repeated every 4 weeks throughout pregnancy. Changepoints in carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation index (AIx), time to wave reflection (T1R), pulse pressure amplification (PPA), and subendocardial viability ratio (SEVR) were compared between women who did and did not subsequently develop PrE. ResultsA changepoint in cfPWV and crPWV was detected at 14–17 weeks' gestation. cfPWV then increased in women who went on to develop PrE but decreased in women who did not; a 1.2 m/s difference in cfPWV between the groups was observed at 22–25 weeks' gestation. Conversely, crPWV converged in the two groups from a baseline difference of 1.05 m/s (95% credible interval: 0.37, 1.72). Women who subsequently developed PrE demonstrated an increase in AIx at 18–21 weeks' gestation that was not seen in women who did not develop PrE until 30–33 weeks. No differences in T1R, PPA, or SEVR were observed between the groups. ConclusionsAltered vascular adaptations were detected using measures of arterial stiffness and wave reflection in the early second trimester of pregnant women who developed PrE compared to those who did not. These findings demonstrate the potential clinical utility of arterial stiffness and wave reflection parameters as an early screening tool for PrE, which can be used to inform clinical management of high-risk pregnancies.

Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials

Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15-2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC.Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.Patient-Centered Outcomes Research Institute.

Role of progestogens in women at risk for spontaneous preterm birth: the final word?

Preterm birth is defined by WHO as delivery before 37 weeks of gestation. 1 WHO: recommended definitions, terminology and format for statistical tables related to the perinatal period and use of a new certificate for cause of perinatal deaths, modifications recommended by FIGO as amended October 14, 1976. Acta Obstet Gynecol Scand. 1977; 56: 247-253 PubMed Google Scholar It is one of the most common pregnancy complications, with an estimated global rate of 10·6% in 2014, equating to an estimated 14·84 million live preterm births. 2 Chawanpaiboon S Vogel JP Moller AB et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019; 7: 37-46 Summary Full Text Full Text PDF PubMed Scopus (962) Google Scholar Preterm birth considerably increases risk of neonatal morbidity and mortality, including long-term sequelae, and can result in long-term health and financial implications for families. 3 Goldenberg RL Culhane JF Iams J Romero R The epidemiology and etiology of preterm birth. Lancet. 2008; 371: 75-84 Summary Full Text Full Text PDF PubMed Scopus (4622) Google Scholar Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trialsVaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Full-Text PDF

Performance of second-trimester maternal biochemistry screening (quadruple test vs. triple test) for trisomy 21: An Indian experience.

Background & objectives:Down syndrome (DS) is one of the most common causes of developmental delay. In India, there is no protocol for prenatal screening of DS. Second-trimester biochemical screening is still being done by triple test. Quadruple test is with better sensitivity and specificity but is not advised routinely. So, the objective of this study was to evaluate the sensitivity and accuracy of the second-trimester screening (quadruple test with genetic sonogram) for trisomy 21 as compared to biochemical testing.Methods:This retrospective observational study was carried out in a Fetal Medicine Centre to analyze the odds of being affected with DS, given a positive risk (OAPR) upon screening in the quadruple test; triple test and quadruple test plus a genetic sonogram for high-risk singleton pregnancies (in view of advanced maternal age; an anomaly scan showing some abnormality, etc).Results:3175 high-risk singleton pregnancies were screened for trisomy 21. 394 women underwent amniocentesis on the basis of triple test, quadruple test or quadruple plus genetic sonogram positive. 17 foetuses were diagnosed to have DS. The quadruple test was found to have a higher OAPR as compared to the triple test (1:30.1 as compared to 1: 40.2). Quadruple test plus the genetic sonogram was found to have the highest OAPR of 1:6.Interpretation & conclusions:Best screening for trisomy 21 is provided with quadruple test with genetic sonogram which can lower the rates of unnecessary amniocentesis in high-risk population.

Cerebroplacental ratio as predictor of adverse perinatal outcome in the third trimester.

IntroductionFetal growth restriction is associated with adverse perinatal outcome and the clinical management of these pregnancies is a challenge. The aim of this study was to investigate the potential of cerebroplacental ratio (CPR) to predict adverse perinatal outcome in high‐risk pregnancies in the third trimester. Another aim was to study whether the CPR has better predictive value than its components, middle cerebral artery (MCA) pulsatility index (PI) and umbilical artery (UA) PI.Material and methodsThe study was a retrospective cohort study including 1573 singleton high‐risk pregnancies with Doppler examinations performed at 32+0 to 40+6 gestational weeks at Lund University Hospital and the University Hospital of Malmö between 29 December 1994 and 31 December 2017. Receiver operating characteristics (ROC) curves were used to investigate the predictive value of the gestational age‐specific z‐scores for CPR, UA PI and MCA PI, respectively, for the primary outcome “perinatal asphyxia/mortality” and the secondary outcomes “birthweight small for gestational age (SGA)” and two composite outcomes: “appropriate for gestational age/large for gestational age liveborn infants with neonatal morbidity” and “SGA liveborn infants with neonatal morbidity.”ResultsThe performance in predicting perinatal asphyxia/mortality was poor for all three variables and did not differ significantly. The ROC area under curve (AUC) was 0.56, 0.55 and 0.53 for CPR, UA PI and MCA PI z‐scores, respectively. The ROC AUC for CPR z‐scores to predict SGA was 0.73, significantly higher than that for either UA PI or MCA PI (P < .001). The ability of CPR and the MCA PI to predict appropriate for gestational age/large for gestational age infant morbidity and SGA infant morbidity was similar and significantly better than UA PI (P < .001).ConclusionsIn the present study, none of the three Doppler measures proved to be useful in predicting perinatal asphyxia and mortality. CPR and MCA PI were equally good in predicting neonatal morbidity, especially in SGA pregnancies, and both were significantly better predictors than the UA PI. CPR had a high predictive value for SGA at birth, better than that of its two components, UA PI and MCA PI.