Approach to dyspnoea in pregnancy in the COVID-19 era.

IMPORTANCE: Dyspnoea and hypoxia in pregnant women during the COVID-19 pandemic may be due to causes other than SARS Co-V-2 infection which should not be ignored. Shared decision-making regarding early delivery is paramount. OBJECTIVE: To highlight and discuss the differential diagnoses of dyspnoea and hypoxia in pregnant women and to discuss the risks versus benefit of delivery for maternal compromise. DESIGN, SETTING AND PARTICIPANTS: Case series of two pregnant women who presented with dyspnoea and hypoxia during the COVID-19 pandemic. RESULTS: Two pregnant women presented with dyspnoea and hypoxia. The first case had COVID-19 infection in the 3rd trimester. The second case had an exacerbation of asthma without concurrent COVID-19. Only the first case required intubation and delivery. Both recovered and were discharged home. Conclusion and relevance: Our two cases highlight the importance of making the correct diagnosis and timely decision-making to consider if delivery for maternal compromise is warranted. Whilst COVID-19 is a current healthcare concern other differential diagnoses must still be considered when pregnant women present with dyspnoea and hypoxia.

Clinical management of nausea and vomiting in pregnancy and hyperemesis gravidarum across primary and secondary care: a population-based study.

OBJECTIVES: To assess how nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) are managed and treated across primary and secondary care. DESIGN: Population-based pregnancy cohort. SETTING: Medical records (CPRD-GOLD) from England. POPULATION: 417 028 pregnancies during 1998-2014. METHODS: Proportions of pregnancies with recorded NVP/HG diagnoses, primary care treatment, and hospital admissions were calculated. Multinomial logistic regression was employed to estimate adjusted relative risk ratios (aRRRs) with 99% confidence intervals (CIs) for the association between NVP/HG management paths and maternal characteristics. MAIN OUTCOME MEASURES: NVP/HG diagnoses, treatments, and hospital admissions. RESULTS: Overall prevalence of clinically recorded NVP/HG was 9.1%: 2.1% had hospital admissions, 3.4% were treated with antiemetics in primary care only, and 3.6% had only recorded diagnoses. Hospital admissions and antiemetic prescribing increased continuously during 1998-2013 (trend P < 0.001). Younger age, deprivation, Black/Asian/mixed ethnicity, and multiple pregnancy were associated with NVP/HG generally across all levels, but associations were strongest for hospital admissions. Most comorbidities had patterns of association with NVP/HG levels. Among women with NVP/HG who had no hospital admissions, 49% were prescribed antiemetics, mainly from first-line treatment (21% prochlorperazine, 15% promethazine, 13% cyclizine) and metoclopramide (10%). Of those admitted, 38% had prior antiemetic prescriptions (34% first-line, 9% second-line, 1% third-line treatment). CONCLUSION: Previous focus on hospital admissions has greatly underestimated the NVP/HG burden. Although primary care prescribing has increased, most women admitted to hospital have no antiemetics prescribed before this. An urgent call is made to assess whether admissions could be prevented with better primary care recognition and timely treatment. TWEETABLE ABSTRACT: The NVP/HG burden is increasing over time and management optimisation should be high priority to help reduce hospital admissions.

The DiPEP study: an observational study of the diagnostic accuracy of clinical assessment, D-dimer and chest x-ray for suspected pulmonary embolism in pregnancy and postpartum.

OBJECTIVE: To identify clinical features associated with pulmonary embolism (PE) diagnosis and determine the accuracy of decision rules and D-dimer for diagnosing suspected PE in pregnant/postpartum women DESIGN: Observational cohort study augmented with additional cases. SETTING: Emergency departments and maternity units at eleven prospectively recruiting sites and maternity units in the United Kingdom Obstetric Surveillance System (UKOSS) POPULATION: 324 pregnant/postpartum women with suspected PE and 198 pregnant/postpartum women with diagnosed PE METHODS: We recorded clinical features, elements of clinical decision rules, D-dimer measurements, imaging results, treatments and adverse outcomes up to 30 days MAIN OUTCOME MEASURES: Women were classified as having PE on the basis of imaging, treatment and adverse outcomes by assessors blind to clinical features and D-dimer. Primary analysis was limited to women with conclusive imaging to avoid work-up bias. Secondary analyses included women with clinically diagnosed or ruled out PE. RESULTS: The only clinical features associated with PE on multivariate analysis were age (odds ratio 1.06; 95% confidence interval 1.01-1.11), previous thrombosis (3.07; 1.05-8.99), family history of thrombosis (0.35; 0.14-0.90), temperature (2.22; 1.26-3.91), systolic blood pressure (0.96; 0.93-0.99), oxygen saturation (0.87; 0.78-0.97) and PE-related chest x-ray abnormality (13.4; 1.39-130.2). Clinical decision rules had areas under the receiver-operator characteristic curve ranging from 0.577 to 0.732 and no clinically useful threshold for decision-making. Sensitivities and specificities of D-dimer were 88.4% and 8.8% using a standard threshold and 69.8% and 32.8% using a pregnancy-specific threshold. CONCLUSIONS: Clinical decision rules and D-dimer should not be used to select pregnant or postpartum women with suspected PE for further investigation. Clinical features and chest x-ray appearances may have counter-intuitive associations with PE in this context. TWEETABLE ABSTRACT: Clinical decision rules and D-dimer are not helpful for diagnosing pregnant/postpartum women with suspected PE.

Longitudinal changes in vascular function parameters in pregnant women with chronic hypertension and association with adverse outcome: a cohort study.

OBJECTIVES: Raised vascular function measures are associated with adverse maternal and perinatal outcomes in low-risk pregnancy. This study aimed to evaluate the association between longitudinal vascular function parameters and adverse outcome in pregnant women with chronic hypertension, and to assess whether these measures vary according to baseline parameters such as black ethnicity. METHODS: This was a nested cohort study of women with chronic hypertension and a singleton pregnancy recruited to the PANDA (Pregnancy And chronic hypertension: NifeDipine vs lAbetalol as antihypertensive treatment) study at one of three UK maternity units. Women had serial pulse-wave analyses performed using the Arteriograph®, while in a sitting position, from 12 weeks' gestation onwards. Statistical analysis was performed using random-effects logistic regression models. Longitudinal vascular parameters were compared between women who developed superimposed pre-eclampsia (SPE) and those who did not, between women who delivered a small-for-gestational-age (SGA) infant (birth weight < 10th centile) and those who delivered an infant with birth weight ≥ 10th centile and between women of black ethnicity and those of non-black ethnicity. RESULTS: The cohort included 97 women with chronic hypertension and a singleton pregnancy, of whom 90% (n = 87) were randomized to antihypertensive treatment and 57% (n = 55) were of black ethnicity, with up to six (mean, three) longitudinal vascular function assessments. SPE was diagnosed in 18% (n = 17) of women and 30% (n = 29) of infants were SGA. In women who developed subsequent SPE, compared with those who did not, mean brachial systolic blood pressure (SBP) (148 mmHg vs 139 mmHg; P = 0.002), mean diastolic blood pressure (DBP) (87 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (139 mmHg vs 128 mmHg; P = 0.001) and mean augmentation index (AIx-75) (29% vs 22%; P = 0.01) were significantly higher across gestation. In women who delivered a SGA infant compared to those who delivered an infant with birth weight ≥ 10th centile, mean brachial SBP (146 mmHg vs 138 mmHg; P = 0.001), mean DBP (86 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (137 mmHg vs 127 mmHg; P < 0.0001) and mean pulse-wave velocity (9.1 m/s vs 8.5 m/s; P = 0.02) were higher across gestation. No longitudinal differences were found in vascular function parameters in women of black ethnicity compared with those of non-black ethnicity. CONCLUSION: There were persistent differences in vascular function parameters and brachial blood pressure throughout pregnancy in women with chronic hypertension who later developed adverse maternal or perinatal outcome. Further investigation into the possible clinical use of these findings is warranted. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Impact of ethnicity on adverse perinatal outcome in women with chronic hypertension: a cohort study.

OBJECTIVE: To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension. METHODS: Demographic and delivery data were collated of women with chronic hypertension and singleton pregnancy who delivered at one of three UK obstetric units between 2000 and 2014. Multivariable logistic regression models were used to calculate risk ratios (RR), according to ethnic group, for adverse perinatal outcome, adjusted for other maternal characteristics including age, parity, body mass index, smoking status, deprivation index and year of delivery. The impact of maternal ethnicity on birth-weight centile calculation was investigated by comparing the birth-weight centile chart customized for ethnicity (Gestation Related Optimal Weight; GROW) with a birth-weight centile calculator that does not adjust for that factor (INTERGROWTH-21st ). RESULTS: The study cohort included 4481 pregnancies (4045 women) with chronic hypertension. Women of white ethnicity accounted for 47% (n = 2122) of the cohort and 36% (n = 1601) were of black, 8.5% (n = 379) of Asian and 8.5% (n = 379) of other ethnicity. The overall incidence of stillbirth was 1.6%, that of preterm birth < 37 weeks was 16% and that of fetal growth restriction (birth weight < 3rd centile) was 11%. Black women, compared with white women, had the highest risk for all adverse perinatal outcomes, with stillbirth occurring in 3.1% vs 0.6% of pregnancies (adjusted RR (aRR), 5.56 (95% CI, 2.79-11.09)), preterm birth < 37 weeks in 21% vs 11% (aRR, 1.70 (95% CI, 1.43-2.01)) and birth weight < 3rd centile in 15% vs 7.4% (aRR, 2.07 (95% CI, 1.71-2.51)). Asian women, compared with white women, were also at increased risk of adverse perinatal outcome, with stillbirth occurring in 1.6% vs 0.6% (aRR, 3.03 (95% CI, 1.11-8.28)), preterm birth < 37 weeks in 20% vs 11% (aRR, 1.82 (95% CI, 1.41-2.35)) and birth weight < 3rd centile in 12% vs 7.4% (aRR, 1.69 (95% CI, 1.24-2.30)). The sensitivity and specificity for prediction of infants requiring neonatal unit admission were 40% and 93%, respectively, for those with birth weight < 3rd centile according to GROW charts, compared with 16% and 96%, respectively, for those with birth weight < 3rd centile according to INTERGROWTH-21st charts. CONCLUSIONS: Black ethnicity, compared with white, is associated with the greatest risk of adverse perinatal outcome in women with chronic hypertension, even after adjusting for other maternal characteristics. Women of Asian ethnicity are also at increased risk, but to a lesser extent. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Exposure to biological therapies during conception and pregnancy: a systematic review.

BACKGROUND: Biological therapies are effective treatments for psoriasis and are often prescribed to women of child-bearing age. OBJECTIVES: To evaluate the safety of biological therapy in conception and/or pregnancy. METHODS: We performed a systematic review of PubMed, MEDLINE, Embase and Cochrane databases for multivariate-adjusted studies of women exposed to biologics relevant to the treatment of psoriasis during conception and/or pregnancy. RESULTS: We identified four population-based cohort studies involving 1300 women exposed to tumour necrosis factor (TNF)-α inhibitors (TNFi) 3 months prior to or during the first 3 months of pregnancy. These studies showed a trend towards drug-specific harm with TNFi exposure in women with different inflammatory diseases, with an increased risk of congenital malformations [three studies; odds ratio (OR) range 1·32-1·64] and preterm birth (one study; OR 1·69, 95% confidence interval 1·10-2·60). This trend did not reach statistical significance in all studies; study heterogeneity, variation across comparator cohorts, inadequate adjustment for important confounding variables such as co-therapy, and an absence of a common constellation of malformations means there is uncertainty about the causal role of TNFi. No studies specifically addressed the effect of TNFi exposure in psoriasis during conception and/or pregnancy, or of interleukin (IL)-17 and IL-12/23 antagonists in any indication. CONCLUSIONS: When counselling women these findings must be balanced against the potential impact of untreated severe psoriasis on conception and/or pregnancy and maternal wellbeing; ongoing pharmacovigilance via registries remains essential to address this evidence gap.

Pregnancies in older women living with HIV in the UK and Ireland.

OBJECTIVES: The aim of the study was to compare maternal characteristics and pregnancy outcomes in women aged < 40 years and ≥ 40 years in a large unselected population of HIV-positive women delivering in the UK and Ireland between 2000 and 2014. METHODS: Comprehensive population-based surveillance data on all HIV-positive pregnant women and their children seen for care in the UK and Ireland are collected through the National Study of HIV in Pregnancy and Childhood. All singleton and multiple pregnancies reported by the end of June 2015 resulting in live birth or stillbirth to women diagnosed with HIV infection before delivery and delivering in 2000-2014 were included. Logistic regression models were fitted in analyses examining the association between older maternal age and specific outcomes (preterm delivery and stillbirth). RESULTS: Among 15 501 pregnancies in HIV-positive women, the proportion in older women (≥ 40 years) increased from 2.1% (73 of 3419) in 2000-2004 to 8.9% (510 of 5748) in 2010-2014 (P < 0.001). Compared with pregnancies in younger women, those in older women were more likely to result in multiple birth (3.0 vs. 1.9% in younger women; P = 0.03), stillbirth (adjusted odds ratio 2.39; P = 0.004) or an infant with a chromosomal abnormality (1.6 vs. 0.2%, respectively; P < 0.001). However, there was no increased risk of preterm delivery, low birth weight or mother-to-child HIV transmission among older mothers. CONCLUSIONS: There has been a significant increase over time in the proportion of deliveries to women living with HIV aged ≥ 40 years, which has implications for pregnancy management, given their increased risk of multiple births, stillbirth and chromosomal anomalies, as also apparent in the general population.

Do adverse pregnancy outcomes contribute to accelerated cardiovascular events seen in young women with systemic lupus erythematosus?

Cardiovascular events (CVEs) are prevalent in patients with systemic lupus erythematosus (SLE), and it is the young women who are disproportionately at risk. The risk factors for accelerated cardiovascular disease remain unclear, with multiple studies producing conflicting results. In this paper, we aim to address both traditional and SLE-specific risk factors postulated to drive the accelerated vascular disease in this cohort. We also discuss the more recent hypothesis that adverse pregnancy outcomes in the form of maternal-placental syndrome and resultant preterm delivery could potentially contribute to the CVEs seen in young women with SLE who have fewer traditional cardiovascular risk factors. The pathophysiology of how placental-mediated vascular insufficiency and hypoxia (with the secretion of placenta-like growth factor (PlGF) and soluble fms-tyrosine-like kinase-1 (sFlt-1), soluble endoglin (sEng) and other placental factors) work synergistically to damage the vascular endothelium is discussed. Adverse pregnancy outcomes ultimately are a small contributing factor to the complex pathophysiological process of cardiovascular disease in patients with SLE. Future collaborative studies between cardiologists, obstetricians, obstetric physicians and rheumatologists may pave the way for a better understanding of a likely multifactorial aetiological process.

Hospital admission for hyperemesis gravidarum: a nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies.

STUDY QUESTION: What are the maternal risk factors for hyperemesis gravidarum (HG) hospital admission, readmission and reoccurrence in a following pregnancy? SUMMARY ANSWER: Young age, less socioeconomic deprivation, nulliparity, Asian or Black ethnicity, female fetus, multiple pregnancy, history of HG in a previous pregnancy, thyroid and parathyroid dysfunction, hypercholesterolemia and Type 1 diabetes are all risk factors for HG. WHAT IS KNOWN ALREADY: Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with a history of HG were previously reported to be at higher risk of developing HG; however, most evidence is from small studies. Little is known about associations with other comorbidities and there is controversy over other risk factors such as parity. Estimates of HG prevalence vary and there is a little understanding of the risks of HG readmission in a current pregnancy and reoccurrence rates in subsequent pregnancies, all of which are needed for planning measures to reduce onset or worsening of the condition. STUDY DESIGN, SIZE, DURATION: We performed a population-based cohort study of pregnancies ending in live births and stillbirths using prospectively recorded secondary care records (Hospital Episode Statistics) from England. We analysed those computerized and anonymized clinical records from over 5.3 million women who had one or more pregnancies between 1997 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained 8 215 538 pregnancies from 5 329 101 women of reproductive age, with a total of 186 800 HG admissions occurring during 121 885 pregnancies. Multivariate logistic regression with generalized estimating equations was employed to estimate odds ratios (aOR) to assess sociodemographic, pregnancy and comorbidity risk factors for HG onset, HG readmission within a pregnancy and reoccurrence in a subsequent pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Being younger, from a less socioeconomically deprived status, of Asian or Black ethnicity, carrying a female fetus or having a multiple pregnancy all significantly increased HG and readmission risk but only ethnicity increased reoccurrence. Comorbidities most strongly associated with HG were parathyroid dysfunction (aOR = 3.83, 95% confidence interval 2.28-6.44), hypercholesterolemia (aOR = 2.54, 1.88-3.44), Type 1 diabetes (aOR = 1.95, 1.82-2.09), and thyroid dysfunction (aOR = 1.85, 1.74-1.96). History of HG was the strongest independent risk factor (aOR = 4.74, 4.46-5.05). Women with higher parity had a lower risk of HG compared with nulliparous women (aOR = 0.90, 0.89-0.91), which was not explained by women with HG curtailing further pregnancies. LIMITATIONS, REASONS FOR CAUTION: Although this represents the largest population-based study worldwide on the topic, the results could have been biased by residual and unmeasured confounding considering that some potential important risk factors such as smoking, BMI or prenatal care could not be measured with these data. Underestimation of non-routinely screened comorbidities such as hypercholesterolemia or thyroid dysfunction could also be a cause of selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The estimated prevalence of 1.5% from our study was similar to the average prevalence reported in the literature and the representativeness of our data has been validated by comparison to national statistics. Also the prevalence of comorbidities was mostly similar to other studies estimating these in the UK and other developed countries. Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with history of HG were confirmed to be at higher risk of HG with an unprecedented higher statistical power. We showed for the first time that socioeconomic status interacts with maternal age, that hypercholesterolemia is a potential risk factor for HG and that carrying multiple females increases risk of hyperemesis compared with multiple males. We also provided robust evidence for the association of parity with HG. Earlier recognition and management of symptoms via gynaecology day-case units or general practitioner services can inform prevention and control of consequent hospital admissions. STUDY FUNDING/COMPETING INTERESTS: The work was founded by The Rosetrees Trust and the Stoneygate Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.N.-P. reports personal fees from Sanofi Aventis, Warner Chilcott, Leo Pharma, UCB and Falk, outside the submitted work and she is one of the co-developers of the RCOG Green Top Guideline on HG; all other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Tacrolimus is an effective treatment for lupus nephritis in pregnancy.

Lupus nephritis during pregnancy increases morbidity and mortality for mother and baby. Flares are difficult to treat as many therapeutic options are teratogenic or fetotoxic. Steroids alone may be unable to control disease activity and are associated with higher rates of preterm delivery, sepsis and gestational diabetes. Reports of using tacrolimus to treat lupus nephritis in pregnancy are limited. We describe the pregnancies of nine women in whom tacrolimus was successfully used to treat lupus nephritis flare (six patients) or maintain stable disease (three patients). Introduction or dose escalation of oral steroids was avoided in five of the patients who developed active disease and steroid dose was rapidly reduced in the sixth patient. All women with disease flare attained partial or complete remission after starting tacrolimus. None of the women on maintenance treatment developed active disease. We propose tacrolimus as an effective adjuvant or alternative therapy to steroids for treating lupus nephritis flare or maintaining stable disease during pregnancy.

Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.

Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 µmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described.

Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome.

Women with antiphospholipid syndrome (APS) may have diverse pregnancy outcomes. The objective of this study was to evaluate pregnancy outcome in women with APS according to their clinical phenotype, i.e. thrombotic and obstetric APS. Eighty-three pregnancies in 67 women with APS were included in the study, including 21 with recurrent miscarriage (Group 1), 21 with late fetal loss or early delivery due to placental dysfunction (Group 2) and 41 with thrombotic APS (Group 3). Group 3 had higher rates of preterm delivery (26.8% versus 4.7%, p = 0.05) than Group 1 and more small for gestational age (SGA) babies than Group 2 (39.5% versus 4.8%, p = 0.003). Group 2 had significantly longer gestations compared with their pretreatment pregnancies (38.4 [28.4-41.4] versus 24.0 [18-35] weeks, p < 0.0001) and 100% live birth rate after treatment with aspirin and low-molecular-weight heparin (LMWH). In conclusion, women with thrombotic APS (Group 3) have higher rates of pregnancy complications than those with obstetric APS (Groups 1 and 2). Treatment with aspirin and LMWH is associated with improved outcomes for women with previous late fetal loss or early delivery due to placental dysfunction (Group 2).

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Tuberculosis in pregnancy in the UK.

Tuberculosis (TB) is a globally important cause of morbidity and mortality with an increasing incidence in women of reproductive ages. This descriptive study using the UK Obstetric Surveillance System demonstrates key differences in the presentation of TB during pregnancy compared with the nonpregnant population. The disease is limited to ethnic minority women, most commonly recent immigrants. Presentation may be atypical, with extrapulmonary disease as common as pulmonary. Clinicians should be aware of the potential for nonspecific presentation of the disease in pregnancy and consider the diagnosis in women, especially recently arrived immigrants, presenting with nonspecific symptoms.