Autoimmune diseases and adverse pregnancy outcomes: an umbrella review.

BACKGROUND: There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area. METHODS: Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported. RESULTS: Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren's syndrome RR 8.85 (95% CI 3.10-25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10-7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08-5.71) and SLE OR 3.20 (2.54-4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47-5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21-4.53) and coeliac disease OR 1.71 (1.36-2.14). Preterm birth was associated with T1DM OR 4.36 (3.72-5.12) and SLE OR 2.79 (2.07-3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54-7.80) and OR 3.80 (2.16-6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44-4.58), IBD OR 1.57 (1.03-2.38), and coeliac disease OR 1.57 (1.17-2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56-0.83). CONCLUSIONS: Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.

Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.

INTRODUCTION: Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy. METHODS AND ANALYSIS: Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

Maternal multimorbidity and preterm birth in Scotland: an observational record-linkage study.

BACKGROUND: Multimorbidity is common in women across the life course. Preterm birth is the single biggest cause of neonatal mortality and morbidity. We aim to estimate the prevalence of multimorbidity in pregnant women and to examine the association between maternal multimorbidity and PTB. METHODS: This is a retrospective cohort study using electronic health records from the Scottish Morbidity Records. All pregnancies among women aged 15 to 49 with a conception date between 1 January 2014 and 31 December 2018 were included. Multimorbidity was defined as the presence of two or more pre-existing long-term physical or mental health conditions, and complex multimorbidity as the presence of four or more. It was calculated at the time of conception using a predefined list of 79 conditions published by the MuM-PreDiCT consortium. PTB was defined as babies born alive between 24 and less than 37 completed weeks of gestation. We used Generalised Estimating Equations adjusted for maternal age, socioeconomic status, number of previous pregnancies, BMI, and smoking history to estimate the effect of maternal pre-existing multimorbidity. Absolut rates are reported in the results and tables, whilst Odds Ratios (ORs) are adjusted (aOR). RESULTS: Thirty thousand five hundred fifty-seven singleton births from 27,711 pregnant women were included in the analysis. The prevalence of pre-existing multimorbidity and complex multimorbidity was 16.8% (95% CI: 16.4-17.2) and 3.6% (95% CI: 3.3-3.8), respectively. The prevalence of multimorbidity in the youngest age group was 10.2%(95% CI: 8.8-11.6), while in those 40 to 44, it was 21.4% (95% CI: 18.4-24.4), and in the 45 to 49 age group, it was 20% (95% CI: 8.9-31.1). In women without multimorbidity, the prevalence of PTB was 6.7%; it was 11.6% in women with multimorbidity and 15.6% in women with complex multimorbidity. After adjusting for maternal age, socioeconomic status, number of previous pregnancies, Body Mass Index (BMI), and smoking, multimorbidity was associated with higher odds of PTB (aOR = 1.64, 95% CI: 1.48-1.82). CONCLUSIONS: Multimorbidity at the time of conception was present in one in six women and was associated with an increased risk of preterm birth. Multimorbidity presents a significant health burden to women and their offspring. Routine and comprehensive evaluation of women with multimorbidity before and during pregnancy is urgently needed.

Prevalence of polypharmacy in pregnancy: a systematic review.

OBJECTIVES: The use of medications among pregnant women has been rising over the past few decades but the reporting of polypharmacy has been sporadic. The objective of this review is to identify literature reporting the prevalence of polypharmacy among pregnant women, the prevalence of multimorbidity in women taking multiple medications in pregnancy and associated effects on maternal and offspring outcomes. DESIGN: MEDLINE and Embase were searched from their inception to 14 September 2021 for interventional trials, observational studies and systematic reviews reporting on the prevalence of polypharmacy or the use of multiple medications in pregnancy were included.Data on prevalence of polypharmacy, prevalence of multimorbidity, combinations of medications and pregnancy and offspring outcomes were extracted. A descriptive analysis was performed. RESULTS: Fourteen studies met the review criteria. The prevalence of women being prescribed two or more medications during pregnancy ranged from 4.9% (4.3%-5.5%) to 62.4% (61.3%-63.5%), with a median of 22.5%. For the first trimester, prevalence ranged from 4.9% (4.7%-5.14%) to 33.7% (32.2%-35.1%). No study reported on the prevalence of multimorbidity, or associated pregnancy outcomes in women exposed to polypharmacy. CONCLUSION: There is a significant burden of polypharmacy among pregnant women. There is a need for evidence on the combinations of medications prescribed in pregnancy, how this specifically affects women with multiple long-term conditions and the associated benefits and harms. TWEETABLE ABSTRACT: Our systematic review shows significant burden of polypharmacy in pregnancy but outcomes for women and offspring are unknown. PROSPERO REGISTRATION NUMBER: CRD42021223966.

Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.

BACKGROUND: The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy. METHODS: A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy. RESULTS: During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy. CONCLUSIONS: The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.

The impact of preconception counselling on maternal and fetal outcomes in women with chronic medical conditions: A systematic review.

BACKGROUND: Beyond diabetes mellitus little data reports outcomes of women with chronic medical conditions who have received pre-conception counselling (PCC). This study aimed to perform a systematic review of the literature to evaluate evidence regarding the impact of PCC on maternal and fetal outcomes in women with chronic medical conditions aside from diabetes mellitus. METHODS: A systematic review was conducted in accordance with PRISMA. PubMed, Cochrane, Ovid Medline and Web of Science were searched. Two reviewers screened abstracts and full texts. Inclusion criteria included studies relating to chronic medical disorders of interest published between database inception and 21st May 2022, reporting outcomes relating to disease activity and perinatal outcomes. RESULTS: The search yielded 11,814 results of which six met criteria for inclusion. Two papers describe the demographics of women more likely to receive PCC which included younger age, shorter disease duration, nulliparity, IVF pregnancy and higher education/job security. Two reported the effects of PCC on women's behaviour with improvements demonstrated in correct medication adherence, folic acid intake and smoking cessation. Five studies reported outcomes related to disease activity; those receiving PCC were more likely to have quiescent disease during pregnancy. Improvements in pregnancy outcomes were described including reduced rates of small for gestational age, low birth weight, preterm birth, congenital abnormality and obstetric complications. DISCUSSION: A paucity of data exists relating to pregnancy outcomes in women with chronic medical conditions receiving PCC. Reported outcomes are favorable, supporting the routine inclusion of PCC in preparation for pregnancy in such patients.

Challenges in management of gastrointestinal cancers in pregnancies: A report of three cases.

Gastrointestinal cancer occurs in approximately 1 in 13,000 pregnancies, making up 4% of malignancies detected in pregnancy. It is a complex and challenging condition to diagnose and manage and is often only detected in its more advanced stages. This is partly due to symptoms of gastrointestinal cancer being incorrectly attributed to physiological symptoms of pregnancy, as well as concerns about the safety of diagnostic investigations in pregnancy, both of which may delay diagnosis and lead to disease progression. Challenges in management also arise from under-treatment in pregnancy due to concerns about the impact of surgery or chemotherapy on the pregnancy. We present here three cases of gastrointestinal cancer diagnosed in pregnancy in our centre and discuss the challenges and pitfalls one may encounter in the diagnosis and management of gastrointestinal malignancies in pregnancy.

Starvation ketosis in a pregnant woman with COVID-19: a case report.

Summary: COVID-19 is associated with severe disease in pregnancy. Complications of the disease, or simultaneous diagnoses, may be missed if clinicians do not retain a large differential diagnosis when assessing such women. Starvation ketoacidosis is one such diagnosis which may complicate the disease and should not be missed. A 37-year-old woman, 33 weeks' gestation presented with breathlessness. Clinical history, examination and investigations supported a diagnosis of starvation ketosis of pregnancy complicating COVID-19 pneumonitis. Prompt correction of the metabolic disturbance resulted in resolution, and preterm delivery was avoided at this time. Early recognition and prompt management of starvation ketosis of pregnancy in women with COVID-19 are important in reducing maternal and neonatal morbidity and mortality. Preterm delivery may be avoided with prompt resolution of the metabolic disturbance. Clinicians should keep a wide differential diagnosis when assessing women with breathlessness. A multidisciplinary team (MDT) approach is required to facilitate optimal care. Learning points: Clinicians should maintain a wide differential when assessing women who are unwell with COVID-19 in pregnancy. Complications such as starvation ketoacidosis are rare but life-threatening. An awareness of such complications facilitates early identification of the condition, and involvement of appropriate specialists who can initiate optimal and timely management. In the context of pregnancy, where ketoacidosis poses a threat to the mother or baby, prompt management and resolution may avoid preterm delivery. Conditions that may increase the risk of developing starvation ketoacidosis include pregnancy, medication use such as corticosteroids or tocolytic therapies, previous gastric surgery, intercurrent illness and pregnancy-related conditions that might contribute towards a degree of chronic starvation. Multidisciplinary input supports the delivery of best practice and care for the patients.

Pharmacovigilance pregnancy data in a large population of patients with chronic inflammatory disease exposed to certolizumab pegol.

Introduction: Chronic inflammatory diseases (CIDs), including rheumatic diseases and other inflammatory conditions, often affect women of reproductive age. Tumor necrosis factor inhibitors (TNFi) are widely used to treat CID, but there is limited information on outcomes of TNFi-exposed pregnancies. We evaluated pregnancy outcomes from 1392 prospectively reported pregnancies exposed to certolizumab pegol (CZP), a PEGylated, Fc-free TNFi with no to minimal placental transfer. Methods: CZP-exposed pregnancies in patients with CID from the UCB Pharmacovigilance global safety database were reviewed from the start of CZP clinical development (July 2001) to 1 November 2020. To limit bias, the analysis focused on prospectively reported cases with known pregnancy outcomes. Results: In total, 1392 prospective pregnancies with maternal CZP exposure and known pregnancy outcomes (n = 1425) were reported; 1021 had at least first-trimester CZP exposure. Live birth was reported in 1259/1425 (88.4%) of all prospective outcomes. There were 150/1425 (10.5%) pregnancy losses before 20 weeks (miscarriage/induced abortion), 11/1425 (0.8%) stillbirths, and 5/1392 (0.4%) ectopic pregnancies. Congenital malformations were present in 30/1259 (2.4%) live-born infants, of which 26 (2.1%) were considered major according to the Metropolitan Atlanta Congenital Defects Program criteria. There was no pattern of congenital malformations. Discussion and conclusion: No signal for adverse pregnancy outcomes or congenital malformations was observed in CZP-exposed pregnancies. Although the limitations of data collected through this methodology (including underreporting, missing information, and absence of a comparator group) should be considered, these data provide reassurance for women with CID who require CZP treatment during pregnancy, and their treating physicians.

Epidemiology of pre-existing multimorbidity in pregnant women in the UK in 2018: a population-based cross-sectional study.

BACKGROUND: Although maternal death is rare in the United Kingdom, 90% of these women had multiple health/social problems. This study aims to estimate the prevalence of pre-existing multimorbidity (two or more long-term physical or mental health conditions) in pregnant women in the United Kingdom (England, Northern Ireland, Wales and Scotland). STUDY DESIGN: Pregnant women aged 15-49 years with a conception date 1/1/2018 to 31/12/2018 were included in this population-based cross-sectional study, using routine healthcare datasets from primary care: Clinical Practice Research Datalink (CPRD, United Kingdom, n = 37,641) and Secure Anonymized Information Linkage databank (SAIL, Wales, n = 27,782), and secondary care: Scottish Morbidity Records with linked community prescribing data (SMR, Tayside and Fife, n = 6099). Pre-existing multimorbidity preconception was defined from 79 long-term health conditions prioritised through a workshop with patient representatives and clinicians. RESULTS: The prevalence of multimorbidity was 44.2% (95% CI 43.7-44.7%), 46.2% (45.6-46.8%) and 19.8% (18.8-20.8%) in CPRD, SAIL and SMR respectively. When limited to health conditions that were active in the year before pregnancy, the prevalence of multimorbidity was still high (24.2% [23.8-24.6%], 23.5% [23.0-24.0%] and 17.0% [16.0 to 17.9%] in the respective datasets). Mental health conditions were highly prevalent and involved 70% of multimorbidity CPRD: multimorbidity with ≥one mental health condition/s 31.3% [30.8-31.8%]). After adjusting for age, ethnicity, gravidity, index of multiple deprivation, body mass index and smoking, logistic regression showed that pregnant women with multimorbidity were more likely to be older (CPRD England, adjusted OR 1.81 [95% CI 1.04-3.17] 45-49 years vs 15-19 years), multigravid (1.68 [1.50-1.89] gravidity ≥ five vs one), have raised body mass index (1.59 [1.44-1.76], body mass index 30+ vs body mass index 18.5-24.9) and smoked preconception (1.61 [1.46-1.77) vs non-smoker). CONCLUSION: Multimorbidity is prevalent in pregnant women in the United Kingdom, they are more likely to be older, multigravid, have raised body mass index and smoked preconception. Secondary care and community prescribing dataset may only capture the severe spectrum of health conditions. Research is needed urgently to quantify the consequences of maternal multimorbidity for both mothers and children.

IBD in pregnancy: recent advances, practical management.

Inflammatory bowel disease (IBD) poses complex issues in pregnancy, but with high-quality care excellent pregnancy outcomes are achievable. In this article, we review the current evidence and recommendations for pregnant women with IBD and aim to provide guidance for clinicians involved in their care. Many women with IBD have poor knowledge about pregnancy-related issues and a substantial minority remains voluntarily childless. Active IBD is associated with an increased risk of preterm birth, low for gestation weight and fetal loss. With the exception of methotrexate and tofacitinib the risk of a flare outweighs the risk of IBD medication and maintenance of remission from IBD should be the main of care. Most women with IBD will experience a normal pregnancy and can have a vaginal delivery. Active perianal Crohn's disease is an absolute and ileal pouch surgery a relative indication for a caesarean section. Breast feeding is beneficial to the infant and the risk from most IBD medications is negligible.

Placental and endothelial biomarkers for the prediction of superimposed pre-eclampsia in chronic kidney disease.

OBJECTIVES: To evaluate PlGF, sFlt-1, and novel endothelial biomarkers hyaluronan and vascular cell adhesion molecule (VCAM), for the prediction of superimposed pre-eclampsia in women with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study of pregnant women with CKD in UK. MAIN OUTCOME MEASURES: Outcomes including superimposed pre-eclampsia were based on predetermined criteria. Test performances of plasma PlGF, serum sFlt-1:PlGF, hyaluronan and VCAM concentrations were evaluated as area under the receiver-operating curve and at established and exploratory threshold concentrations. RESULTS: There were 232 pregnancies in 221 women with CKD. One third (76/232) developed superimposed pre-eclampsia. From 21 to 37 weeks' gestation, plasma PlGF was decreased among women that developed superimposed preeclampsia. Plasma PlGF levels < 150 pg/ml had the highest sensitivity (79% 95% CI: 58-91%) and negative predictive value (97%, 95% CI: 93-99%) for the prediction of delivery with superimposed pre-eclampsia within 14 days. Predictive performances of hyaluronan and VCAM were lower than for plasma PlGF. Low plasma PlGF, high hyaluronan and high VCAM concentrations had lower predictive performance in women with pre-pregnancy CKD stages 3-5 compared to stages 1-2. sFlt-1:PlGF > 38 did not usefully predict the need to deliver in women with CKD when measured in serum. CONCLUSIONS: Increased surveillance for the need for delivery should take place in women with CKD and plasma PlGF below 150 pg/ml after 20 weeks' gestation, with awareness that predictive value is reduced as excretory kidney function declines. Maternal endothelial dysfunction may alter the PlGF threshold at which superimposed pre-eclampsia manifests in women with CKD.

Midterm outcomes in postpartum women following endovenous treatment for acute iliofemoral deep vein thrombosis.

BACKGROUND: The development of post-thrombotic syndrome (PTS) after iliofemoral deep vein thrombosis (DVT) continues to be a considerable issue for both pregnant and postpartum women with rates as high as 70% among those managed with anticoagulation alone. This study aims to characterize the outcomes of interventional treatment for acute iliofemoral DVT in this at-risk population. METHODS: A retrospective analysis of all postpartum patients treated for acute iliofemoral DVT with lysis and stenting between January 2012 and December 2017 at a referral center. Patient demographics, risk factors, procedural factors. and complications were collected. Post-treatment outcomes were compared with all nonpostpartum females treated within the same time period. These included the severity of PTS evaluated using the Villalta scale, duration of vessel patency and factors affecting reintervention timing and success. Further detailed review of cases needing reintervention was also conducted through a retrospective review of documentation and an analysis of all imaging by a consultant radiologist. RESULTS: A total of 11 postpartum women were identified. The median age was 28 years (range, 22-41 years) and intervention was performed at a median of 3 weeks after birth (range 2-12 weeks). No major or minor complications associated with intervention were reported in any patients. The median Villalta score was 3 at 6 months, improving to 2 at 12 months. Overall, two patients were classified as mild having PTS (18%), with no cases of moderate to severe PTS. On comparison with nonpostpartum (n = 68) Villalta scores, no significant difference in outcome was observed at 6 months (median score, 3; range, 0-15 months; P = .95) or at 1 year (median score, 1; range, 0-15; P = .84). Cumulative patency at 1 year was found to be 64% in postpartum women compared with 93% in nonpostpartum women. The postpartum state was found to be a significant predictor of cumulative patency loss (hazard ratio, 0.10; 95% confidence interval, 0.02-0.62; P = .01). However, no significant difference in primary and primary-assisted patency was observed. Of the postpartum patients, 55% required reintervention (6/11) compared with 29% of nonpostpartum patients (20/68). The mean time to initial reintervention was 62 days (range, 7-233 days). Reintervention was unsuccessful in all cases presenting with 100% vessel occlusion (4/11), but successful in both cases with partial occlusion (2/11). Analysis of the etiologic factors associated with reintervention revealed that all reintervention cases were associated with technical failure to fully lyse and stent beyond residual disease at the initial procedure. No technical, flow, or hematologic factors were identified in the four cases that retained primary patency. CONCLUSIONS: This study suggests that percutaneous intervention to achieve early thrombus removal and venous stenting provides a favorable alternative to conservative therapies owing to its potential to decrease the severity of PTS. Completion of lysis and adequate stenting of disease is essential to prevent reocclusion, for which reintervention carries a lower likelihood of success. Further research is warranted to further characterize the appropriate management of postpartum women with iliofemoral DVT.

Seventeen Cases of Primary Hyperparathyroidism in Pregnancy: A Call for Management Guidelines.

CONTEXT: The risks of primary hyperparathyroidism (pHPT) to pregnant women and their fetuses appear to increase commensurate with serum calcium levels. The management strategy for pHPT must be adapted in pregnancy and should reflect the severity of hypercalcemia. However, no guidelines exist to assist clinicians. METHODS: The experience of a high-volume multidisciplinary endocrine surgical service in treating a consecutive series of pregnant women with pHPT referred for parathyroidectomy is presented and data are compared with a nonpregnant cohort with pHPT. A review of pHPT and pregnancy outcomes in the literature is provided. RESULTS: Seventeen pregnant women and 247 age range-matched nonpregnant women with pHPT were referred for surgery over 11 years. Mean serum calcium level was higher in the pregnant cohort (2.89 vs 2.78 mmol/L; P = 0.03). Preoperative localization with ultrasound succeeded in eight pregnant women (47%) and sestamibi scanning did in two of six (33% imaged preconception), compared with 84 (34%) and 102 (42%) control subjects, respectively (not significant). Parathyroidectomy was performed under general anesthesia between 12 and 28 weeks' gestation with no adverse pregnancy outcomes resulting. Cure rate was 100% vs 96% in controls. CONCLUSION: pHPT in pregnancy is a threat to mother and child. Medical management may be appropriate in mild disease, but in moderate to severe disease, parathyroidectomy under general anesthesia in the second trimester is safe. Localization using ionizing radiation/MRI is unnecessary, because surgical intervention in a high-volume multidisciplinary setting has excellent outcomes. Guidelines on the topic would assist clinicians.

Selecting pregnant or postpartum women with suspected pulmonary embolism for diagnostic imaging: the DiPEP diagnostic study with decision-analysis modelling.

BACKGROUND: Pulmonary embolism (PE) is a leading cause of death in pregnancy and post partum, but the symptoms of PE are common in normal pregnancy. Simple diagnostic tests are needed to select women for diagnostic imaging. OBJECTIVE: To estimate the accuracy, effectiveness and cost-effectiveness of clinical features, decision rules and biomarkers for selecting pregnant or postpartum women with a suspected PE for imaging. DESIGN: An expert consensus study to develop new clinical decision rules, a case-control study of women with a diagnosed PE or a suspected PE, a biomarker study of women with a suspected PE or diagnosed deep-vein thrombosis (DVT) and decision-analysis modelling. SETTING: Emergency departments and consultant-led maternity units. PARTICIPANTS: Pregnant/postpartum women with a diagnosed PE from any hospital reporting to the UK Obstetric Surveillance System research platform and pregnant/postpartum women with a suspected PE or diagnosed DVT at 11 prospectively recruiting sites. INTERVENTIONS: Clinical features, decision rules and biomarkers. MAIN OUTCOME MEASURES: Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, quality-adjusted life-years (QALYs) and health-care costs. RESULTS: The primary analysis involved 181 women with PE and 259 women without PE in the case-control study and 18 women with DVT, 18 with PE and 247 women without either in the biomarker study. Most clinical features showed no association with PE. The AUROC curves for the clinical decision rules were as follows: primary consensus, 0.626; sensitive consensus, 0.620; specific consensus, 0.589; PE rule-out criteria, 0.621; simplified Geneva score, 0.579; Wells's PE criteria (permissive), 0.577; and Wells's PE criteria (strict), 0.732. The sensitivities and specificities of the D-dimer measurement were 88.4% and 8.8%, respectively, using a standard threshold, and 69.8% and 32.8%, respectively, using a pregnancy-specific threshold. Previous venous thromboembolism, long-haul travel, multiple pregnancy, oxygen saturation, recent surgery, temperature and PE-related chest radiograph abnormality were predictors of PE on multivariable analysis. We were unable to derive a rule through multivariable analysis or recursive partitioning with adequate accuracy. The AUROC curves for the biomarkers were as follows: activated partial thromboplastin time - 0.669, B-type natriuretic peptide - 0.549, C-reactive protein - 0.542, Clauss fibrinogen - 0.589, enzyme-linked immunosorbent assay D-dimer - 0.668, Innovance D-dimer (Siemens Healthcare Diagnostics Products GmbH, distributed by Sysmex UK Ltd, Milton Keynes, UK) - 0.651, mid-regional pro-atrial natriuretic peptide (MRproANP) - 0.524, prothrombin fragment 1 + 2 - 0.562, plasmin-antiplasmin - 0.639, Prothombin time - 0.613, thrombin generation lag time - 0.702, thrombin generation endogenous potential - 0.559, thrombin generation peak - 0.596, thrombin generation time to peak - 0.655, tissue factor - 0.531 and troponin - 0.597. The repeat analysis excluding women who had received anticoagulation was limited by the small number of women with PE (n = 4). The health economic analysis showed that a strategy of scanning all women with a suspected PE accrued more QALYs and incurred fewer costs than any selective strategy based on a clinical decision rule and was therefore the dominant strategy. LIMITATIONS: The findings apply specifically to the diagnostic assessment of women with a suspected PE in secondary care. CONCLUSIONS: Clinical features, decision rules and biomarkers do not accurately, effectively or cost-effectively select pregnant or postpartum women with a suspected PE for diagnostic imaging. FUTURE WORK: New diagnostic technologies need to be developed to detect PE in pregnancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21245595. FUNDING DETAILS: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 47. See the NIHR Journals Library website for further project information.

Biomarkers for Adverse Pregnancy Outcomes in Rheumatic Diseases.

Pregnancy is a delicate balance of angiogenic factors. Adverse pregnancy outcomes in the form of placental insufficiency occur when antiangiogenic factors predominate, which manifests as maternal-placental syndrome (MPS). Women with rheumatic disease are at increased risk of MPS. Endothelial damage from circulating antiangiogenic factors and other inflammatory molecules in combination with preexisting maternal vascular risk factors is the likely underlying pathophysiological process for MPS. It is likely that these changes persist, and additional "insults" from ongoing inflammation, medications, and disease damage contribute to the development of accelerated cardiovascular disease seen in young women with rheumatic disease.

Adverse Pregnancy Outcomes Among Women with Inflammatory Bowel Disease: A Population-Based Study from England.

BACKGROUND: There is limited contemporary population-based evidence on adverse birth outcomes and pregnancy-related complications for women with inflammatory bowel disease (IBD). This study provides such estimates of these risks and assesses variation by IBD type and surgical interventions. METHODS: We calculated the proportion of pregnancies in women with and without IBD between 1997 and 2012 throughout England using linked primary (Clinical Practice Research Datalink) and secondary care (Hospital Episode Statistics) data. Risk of pregnancy-related complications and adverse birth outcomes in women with Crohn's disease and ulcerative colitis were compared with risks in women without IBD using odds ratios (ORs). RESULTS: Of 364,363 singleton pregnancies resulting in live or stillbirths, 1969 (0.5%) were in women with IBD. Women with Crohn's disease were more likely to have preterm births (OR = 1.42; 95% confidence interval, 1.12-1.79), babies with low birth weights (OR = 1.39; 95% confidence interval, 1.05-1.83), and postpartum hemorrhage (OR = 1.27; 95% confidence interval, 1.04-1.55), whereas women with ulcerative colitis were only at increased risk of preterm births with an absolute risk difference of <2.7%. These risks remained independent of caesarean section. Prior surgery for IBD did not increase the risk of adverse birth outcomes or pregnancy-related complications compared with cases without surgery, however, women with IBD were more likely to have an elective caesarean section. CONCLUSIONS: Women with Crohn's disease have increased risks of some specific pregnancy-related complications and adverse birth outcomes which are independent of caesarean section, however, the absolute risk differences are small, indicating that most women with IBD will have an uncomplicated pregnancy.

Chronic anorexia and weight loss due to extensive fibroid compression of the bowel: an unusual complication of uterine fibroids in a patient with a twin pregnancy.

A 36-year-old homeless Eritrean nulliparous woman was admitted to hospital, with abdominal pain, nausea and loss of appetite. She was found to be 17 weeks pregnant with dichorionic diamniotic twins. She was cachectic and had large palpable uterine fibroids. An extensive search for infection and malignancy did not yield any significant results. She was managed with enteral nutritional support and delivered healthy twins by emergency caesarean section at 36 weeks' gestation. She re-presented 19 days postpartum, with fever and abdominal pain. Imaging revealed multiple abdominal collections and large degenerating fibroids. At laparotomy, the fibroids were found to be adherent to, compressing and enveloping large sections of bowel. The patient required a right hemicolectomy, small bowel resection and total abdominal hysterectomy. Histology confirmed an infarcted leiomyoma and the patient made a good postoperative recovery.

Diagnostic and predictive biomarkers for pre-eclampsia in patients with established hypertension and chronic kidney disease.

Women with chronic kidney disease (CKD) and chronic hypertension (CHT) frequently develop superimposed pre-eclampsia, but distinction from pre-existing disease is challenging. Plasma placental growth factor (PlGF), B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and serum relaxin concentrations were quantified in a longitudinal prospective cohort of 121 women with CKD: 44 with chronic hypertension, and 79 healthy controls. Biomarker concentrations were compared with 32 women with pre-eclampsia without pre-existing disease. Test performance was evaluated for diagnosis of superimposed pre-eclampsia requiring delivery within 14 days of sampling. PlGF was evaluated as a promising marker in a validation cohort of women with suspected pre-eclampsia (29 with CKD; 94 with chronic hypertension; 29 with superimposed pre-eclampsia requiring delivery within 14 days) and compared with women without pre-existing disease (290 with no pre-eclampsia and 176 with pre-eclampsia requiring delivery within 14 days). From 20 and up to 42 weeks of gestation, lower maternal PlGF concentrations had high diagnostic accuracy for superimposed pre-eclampsia requiring delivery within 14 days (receiver operator characteristic 0.85) and confirmed in the validation cohort. The other plasma and serum biomarkers were not discriminatory. Thus, plasma PlGF concentrations could potentially help guide clinical decision making regarding admission and delivery for superimposed pre-eclampsia.