A successful antenatal outcome in a patient with refractory Takayasu's arteritis treated with tocilizumab throughout pregnancy-a case report.

Takayasu's arteritis (TA) is a rare form of large-vessel vasculitis for which tocilizumab (TCZ) may be administered in resistant or refractory disease. Current British Society of Rheumatology advice is to stop TCZ 3-months pre-conception. We report the case of a 33-year-old woman with extensive TA treated with TCZ, azathioprine and glucocorticoids in pregnancy. She was closely monitored with MDT input and TCZ was continued throughout pregnancy as the benefits were thought to outweigh the risks. Our case also highlights the importance of accurate blood pressure monitoring in an appropriate anatomical location, given the extent of her disease. Our patient's disease remained stable throughout the antenatal and post-partum period with a successful pregnancy outcome and no maternal or foetal complications. TCZ is suitable for select cases of refractory TA during pregnancy.

Pregnancy outcomes of a joint obstetric and rheumatology clinic in a tertiary centre: a 2-year retrospective study of 98 pregnancies.

Objectives: The purpose of this study was to describe the maternal and fetal outcomes in patients with inflammatory rheumatic diseases attending a joint rheumatology and obstetric clinic in the UK. Methods: Electronic records of 98 patients attending the joint rheumatology and obstetric clinic between January 2018 and January 2020 were analysed. Data on patient demographics, characteristics (including age, ethnicity, diagnosis, and medications taken during pregnancy), pregnancy outcomes (miscarriage, stillbirth or live birth), maternal complications [infection, post-partum haemorrhage (PPH) or pre-eclampsia] and fetal complications (sepsis, congenital heart block, prematurity and low birth weight) were tabulated. Subgroups of patients based on maternal diagnosis, medications and Ro/La antibody status were described in a similar manner. Results: The cohort was found to be predominantly Caucasian women >30 years of age, diagnosed with a CTD. Of 98 pregnancies, 97% (n = 95) resulted in a live birth, with only 2% resulting in miscarriage (n = 2) and 1% in stillbirth (n = 1). The median duration of gestation was 38 (interquartile range 37-39) weeks, and the majority of patients had a normal vaginal delivery (35%, n = 34), whereas 30% had emergency Caesarean sections (n = 29). The median birth weight was 3120 (interquartile range 2690-3410) g. The most common maternal complications were PPH (56%, n = 54) and infection (22%, n = 21). The most common fetal complications were prematurity (23%, n = 22) and low birth weight (17%, n = 16). Conclusion: We report favourable outcomes from this service model, including a high live birth rate, a low miscarriage rate and a high median birth weight. With limited reported data of pregnancy outcomes from joint obstetric/rheumatology clinics, this service model might be beneficial in other centres.

The impact of COVID-19 on pregnancy outcomes in a diverse cohort in England.

There is conflicting evidence regarding the effect of coronavirus disease (COVID-19) in pregnancy. Risk factors for COVID-19 overlap with risk factors for pregnancy complications. We aimed to assess the effects of the COVID-19 pandemic and confirmed SARS-CoV-2 infection on pregnancy outcomes. A retrospective interrupted time-series and matched cohort analysis was performed. Singleton pregnancies completed between 1st January 2016 and 31st January 2021 were included. Trends in outcomes were analysed over time. Modelled COVID-19 transmission data were applied to deliveries since 1st January 2020 to assign a risk of COVID-19 to each pregnancy, and incorporated into a regression model of birthweight. Confirmed COVID-19 cases were matched to controls delivered in the pre-pandemic period, and maternal and neonatal outcomes compared. 43,802 pregnancies were included, with 8343 in the model of birthweight. There was no increase in the risk of stillbirth (p = 0.26) or neonatal death (p = 0.64) during the pandemic. There was no association between modelled COVID-19 attack rate (%) in any trimester and birthweight (first trimester p = 0.50, second p = 0.15, third p = 0.16). 214 COVID-positive women were matched to controls. Preterm birth was more common in symptomatic cases (14/62, 22.6%) compared to asymptomatic cases (9/109, 8.3%, p = 0.008) and controls (5/62, 8.1%, p = 0.025). Iatrogenic preterm birth was more common in cases (21/214, 9.8%) than controls (9/214, 4.2%, p = 0.02). All other examined outcomes were similar between groups. There was no significant impact of COVID-19 on the examined birth outcomes available. Symptomatic COVID-19 should be considered a risk factor for preterm birth, possibly due to an increase in iatrogenic deliveries for maternal indications.

Intra-placental arterial Doppler: A marker of fetoplacental vascularity in late-onset placental disease?

INTRODUCTION: Late-gestation adverse pregnancy outcome is associated with reduced placental villous vascularity but rarely with a frankly abnormal umbilical artery Doppler waveform. The clinical utility of umbilical artery Doppler velocimetry in late gestation is limited by poor understanding of what aspect(s) of placental structure and function the impedance reflects. We hypothesized that placental arterial circulation impedance reflects placental vascularity and arterial function. MATERIAL AND METHODS: This was a secondary analysis of data from the FEMINA2 study, a study of pregnancy outcome after reduced fetal movement. Forty-three pregnancies that delivered within 7 days of ultrasound assessment were examined. Impedance was quantified by pulsatility index (PI) from umbilical, chorionic plate arteries, and intra-placental arteries. Site-specific PI was compared with villous vascularity (CD31 immunostaining) and placental arterial function (wire myography) by regression analysis (P < .01) where factor analysis suggested potential co-variance (Eigen value > 2). RESULTS: Pulsatility index decreased with proximity to the placental microvasculature (P < .0001). Intra-placental artery PI correlated significantly with vessel number (R2  = 0.40, P = .0007). No significant relations between umbilical or chorionic plate artery PI and villous vascularity were found (P ≥ .11 and P ≥ .042). No significant co-variance was suggested between PI at any Doppler sampling site and ex vivo placental arterial function indices. Measurement reliability (intraclass correlation coefficient) was highest in the umbilical artery (PI 0.75 and 0.50 for intra- and interoperator reliability, respectively) and lowest in the intra-placental arteries (PI 0.55 and 0.41, respectively). Systematic bias in umbilical artery PI was observed between observers, but not at other Doppler sampling sites. CONCLUSIONS: More vascular placentas ex vivo are associated with reduced intra-placental artery Doppler impedance in utero. Although umbilical (but not intra-placental) artery Doppler PI is associated with adverse outcome after reduced fetal movement, this predictive ability does not appear to be through assessment of placental vascularity or chorionic plate arterial function. The inferior reliability of intra-placental artery Doppler, although similar to previously published reliability of umbilical artery Doppler, impairs its ability to detect subtle differences in placental vascularity, and must be significantly improved before it could be considered a clinically useful test.

'To test or not to test', the arguments for and against thrombophilia testing in obstetrics.

Clinicians increasingly investigate women for thrombophilias due to their associations with venous thromboembolism and placenta-mediated pregnancy complication. These associations, however, are modest and based largely on retrospective data from studies with heterogeneous classifications and populations, leading to discordance between evidence and guidelines. Current evidence suggests a contributory rather than causative role for thrombophilia in placenta-mediated pregnancy complication and venous thromboembolism. With little evidence of benefit from antithrombotic therapy in placenta-mediated pregnancy complication, thrombophilia screening remains controversial. Given the low absolute risk of placenta-mediated pregnancy complication and gestational venous thromboembolism with heritable thrombophilia, universal screening is inappropriate. Selective screening for antiphospholipid syndrome is supported by robust evidence of benefit. Conversely, selective screening for heritable thrombophilia has not been shown to effectively manage placenta-mediated pregnancy complication. Therefore, at present heritable thrombophilia screening is not warranted for placenta-mediated pregnancy complication. Until we have better evidence from better stratified patient groups, caution should remain if we wish to practice evidence-based medicine.

Fractional fetal thigh volume in the prediction of normal and abnormal fetal growth during the third trimester of pregnancy.

BACKGROUND: Currently, 2-dimensional ultrasound estimation of fetal size rather than fetal growth is used to define fetal growth restriction, but single estimates in late pregnancy lack sensitivity and may identify small for gestational age rather than growth restriction. Single or longitudinal measures of 3-dimensional fractional thigh volume may address this problem. OBJECTIVE: We sought to derive normal values for 3-dimensional fractional thigh volume in the third trimester, determine if fractional thigh volume is superior to 2-dimensional ultrasound biometry alone for detecting fetal growth restriction, and determine whether individualized growth assessment parameters have the potential to identify fetal growth restriction remote from term delivery. STUDY DESIGN: This was a longitudinal prospective cohort study of 115 unselected pregnancies in a tertiary referral unit (St Mary's Hospital, Manchester, United Kingdom). Standard 2-dimensional ultrasound biometry measurements were obtained, along with fractional thigh volume measurements (based on 50% of the femoral diaphysis length). Measurements were used to calculate estimated fetal weight (Hadlock). Individualized growth assessment parameters and percentage deviations in longitudinally measured biometrics were determined using a Web-based system (iGAP; http://iGAP. RESEARCH: bcm.edu). Small for gestational age was defined <10th and fetal growth restriction <3rd customized birthweight centile. Logistic regression was used to compare estimated fetal weight (Hadlock), estimated fetal weight (biparietal diameter-abdominal circumference-fractional thigh volume), fractional thigh volume, and abdominal circumference for the prediction of small for gestational age or fetal growth restriction at birth. Screening performance was assessed using area under the receiver operating characteristic curve. RESULTS: There was a better correlation between fractional thigh volume and estimated fetal weight ((biparietal diameter-abdominal circumference-fractional thigh volume) obtained at 34-36 weeks with birthweight than between 2-dimensional biometry measures such as abdominal circumference and estimated fetal weight (Hadlock). There was also a modest improvement in the detection of both small for gestational age and fetal growth restriction using fractional thigh volume-derived measures compared to standard 2-dimensional measurements (area under receiver operating characteristic curve, 0.86; 95% confidence interval, 0.79-0.94, and area under receiver operating characteristic curve, 0.92; 95% confidence interval, 0.85-0.99, respectively). CONCLUSION: Fractional thigh volume measurements offer some improvement over 2-dimensional biometry for the detection of late-onset fetal growth restriction at 34-36 weeks.

Intraexaminer and Interexaminer Variability in 3D Fetal Volume Measurements During the Second and Third Trimesters of Pregnancy.

OBJECTIVES: To assess intraexaminer and interexaminer reliability of 3-dimensional fetal sonographic measurements. METHODS: Three-dimensional fetal organ volumes (head, kidney, total thigh volume, and fractional thigh volume) were acquired during the second and third trimesters, with the addition of placental volume in the second trimester, by 2 different experienced, blinded sonographers. Fifty-eight fetuses were examined from 21 to 39 weeks' gestation. Intraexaminer and Interexaminer reliability was assessed with Bland-Altman plots, and their 95% limits of agreement and intraclass correlation coefficients. RESULTS: The most significant interexaminer error was observed in the second-trimester kidney volume (95% limits of agreement, ± 110%), and the best agreement was for the third-trimester fractional thigh volume (95% limits of agreement, ± 25%) and second-trimester head volume (95% limits of agreement, -7%-25%). Second- and third-trimester intraclass correlation coefficient results were all greater than 0.75, apart from second-trimester kidney volume intraexaminer (0.374) and interexaminer (0.061) measurements, second-trimester placenta interexaminer measurements (0.390), and third-trimester kidney interexaminer measurements (0.647). CONCLUSIONS: Three-dimensional fetal sonographic volumes of the head, kidney, total thigh, and placenta have limited reproducibility, and improvements in measurement techniques are needed before they can be used routinely to assess fetal growth. The 3-dimensional fractional thigh volume can be reliably obtained in the late third trimester.

Management of inherited thrombophilia in pregnancy.

Adverse pregnancy outcomes, such as pregnancy loss and pre-eclampsia, are associated with thrombotic mechanisms and thrombophilia. Antithrombotic interventions, particularly low-molecular-weight heparin, have been investigated in women identified by previous pregnancy outcome; however, the results have been inconsistent. This may reflect heterogeneity of both the study groups and the disease processes resulting in inadequate stratification to guide antithrombotic interventions. Furthermore, the variation in gestation at initiation of low-molecular-weight heparin treatment might be important. Despite limited evidence of efficacy, low-molecular-weight heparin is often used in an attempt to prevent these complications, owing to the lack of other effective treatments and its perceived safety in pregnancy. Research is required to better understand the disease processes, identify possible biomarkers and thereby more homogeneous groups for targeted treatment.

Thrombophilia and Pregnancy Complications.

There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question.

Pulmonary thrombo-embolism in pregnancy: diagnosis and management.

KEY POINTS: Venous thromboembolism (VTE) in pregnancy remains a leading cause of direct maternal mortality in the developed world and identifiable risk factors are increasing in incidence.VTE is approximately 10-times more common in the pregnant population (compared with non-pregnant women) with an incidence of 1 in 1000 and the highest risk in the postnatal period.If pulmonary imaging is required, ventilation perfusion scanning is usually the preferred initial test to detect pulmonary embolism within pregnancy. Treatment should be commenced on clinical suspicion and not be withheld until an objective diagnosis is obtained.The mainstay of treatment for pulmonary thromboembolism in pregnancy is anticoagulation with low molecular weight heparin for a minimum of 3 months in total duration and until at least 6 weeks postnatal. Low molecular weight heparin is safe, effective and has a low associated bleeding risk. EDUCATIONAL AIMS: To inform readers about the current guidance for diagnosis and management of pulmonary thromboembolism in pregnancy.To highlight the risks of venous thromboembolism during pregnancy.To introduce the issues surrounding management of pulmonary thromboembolism around labour and delivery.