Case series of COVID-19 infection in pregnancy complicated by ketoacidosis and symptomatic breathlessness.

Background: The differential diagnosis of acute shortness of breath in a pregnant woman with COVID-19 is broad. Pregnancy is a ketosis-prone state, which can result in metabolic acidosis and tachypnoea. Methods: We describe four pregnant women with COVID-19 and breathlessness where ketoacidosis was found to contribute to symptomatic tachypnoea. Results: One patient did not have associated COVID-19 pneumonitis, but presented with severe tachypnoea and metabolic acidosis; three women had pneumonitis and metabolic acidosis. Corrective treatment for the metabolic abnormalities resulted in resolution of the ketoacidosis in all cases. No women had coexistent diabetes. Conclusion: This is the first series of COVID-19 in pregnancy complicated by ketoacidosis and symptomatic tachypnoea. Ketoacidosis associated with COVID-19 is an important cause of tachypnoea requiring specific treatment, which should not be overlooked. Potential mechanisms for this are discussed with a framework for interpretation of blood gas results during pregnancy.

Maternal glucose homeostasis is impaired in mouse models of gestational cholestasis.

Women with intrahepatic cholestasis of pregnancy (ICP), a disorder characterised by raised serum bile acids, are at increased risk of developing gestational diabetes mellitus and have impaired glucose tolerance whilst cholestatic. FXR and TGR5 are modulators of glucose metabolism, and FXR activity is reduced in normal pregnancy, and further in ICP. We aimed to investigate the role of raised serum bile acids, FXR and TGR5 in gestational glucose metabolism using mouse models. Cholic acid feeding resulted in reduced pancreatic ß-cell proliferation and increased apoptosis in pregnancy, without altering insulin sensitivity, suggesting that raised bile acids affect ß-cell mass but are insufficient to impair glucose tolerance. Conversely, pregnant Fxr-/- and Tgr5-/- mice are glucose intolerant and have reduced insulin secretion in response to glucose challenge, and Fxr-/- mice are also insulin resistant. Furthermore, fecal bile acids are reduced in pregnant Fxr-/- mice. Lithocholic acid and deoxycholic acid, the principal ligands for TGR5, are decreased in particular. Therefore, we propose that raised serum bile acids and reduced FXR and TGR5 activity contribute to the altered glucose metabolism observed in ICP.

The metabolic profile of intrahepatic cholestasis of pregnancy is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth.

OBJECTIVE: Quantification of changes in glucose and lipid concentrations in women with intrahepatic cholestasis of pregnancy (ICP) and uncomplicated pregnancy and study of their influence on fetal growth. RESEARCH DESIGN AND METHODS: A prospective study comparing metabolic outcomes in cholestastic and uncomplicated singleton pregnancies was undertaken at two university hospitals in the U.K. and U.S. from 2011-2014. A total of 26 women with ICP and 27 control pregnancies with no prior history of gestational diabetes mellitus were recruited from outpatient antenatal services and followed until delivery. Alterations in glucose, incretins, cholesterol, and triglycerides were studied using a continuous glucose monitoring (CGM) system and/or a standard glucose tolerance test (GTT) in conjunction with GLP-1 and a fasting lipid profile. Fetal growth was quantified using adjusted birth centiles. RESULTS: Maternal blood glucose concentrations were significantly increased in ICP during ambulatory CGM (P < 0.005) and following a GTT (P < 0.005). ICP is characterized by increased fasting triglycerides (P < 0.005) and reduced HDL cholesterol (P < 0.005), similar to changes observed in metabolic syndrome. The offspring of mothers with ICP had significantly larger customized birth weight centiles, adjusted for ethnicity, sex, and gestational age (P < 0.005). CONCLUSIONS: ICP is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. These findings may have implications regarding the future health of affected offspring.

Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes.

OBJECTIVE: To evaluate the association between intrahepatic cholestasis of pregnancy (ICP) and gestational diabetes mellitus (GDM). STUDY DESIGN: A retrospective case-control study of pregnancy outcomes in 57,724 women managed at a university teaching hospital in Rhode Island, USA, in whom universal screening for GDM had been performed and who were assessed for the incidence of ICP. Pregnancies complicated by ICP or GDM between February 2005 and June 2011 were identified from the electronic patient records using appropriate ICD codes. A total of 125 cases were required to detect a difference in the incidence of GDM in ICP at 5% significance with 80% power. Demographic and clinical outcome data (including maternal age, ethnic group, BMI, and infant weight and gender) were also collected. RESULTS: Of the 57,724 pregnancies, 143 were complicated by ICP (0.25%) and 4880 by GDM (8.5%). Nineteen ICP cases had GDM. The incidence of GDM in ICP was 13.6% (19/140, OR 1.68 CI 1.04-2.72). Where gestational ages were available (n=105), of those screened for GDM prior to developing ICP, 13.4% (11/82, OR 1.64 CI 0.88-3.06) had a confirmed diagnosis, rising to 30% (7/23, OR 4.69 CI 1.98-11.1) in cases that were screened following the onset of cholestasis. Simple linear regression analysis of adjusted birth weight centiles in ICP revealed a significant linear trend of increasing centiles with gestational age (p=0.005). CONCLUSIONS: These data support the hypothesis that the incidence of GDM is higher in women predisposed to developing ICP. It is likely that this susceptibility increases further following the onset of cholestasis.

Behçet's syndrome in pregnancy.

Behçet's syndrome (BS), a systemic inflammatory disease characterized by oral and genital ulceration, eye inflammation and arthritis, usually presents in the third and fourth decades of life, but is rare in pregnancy. BS is not usually associated with a detrimental effect on pregnancy outcome. In most women BS is reported to improve in pregnancy, although it may not always follow a similar course in successive pregnancies and it is not possible to predict the course of BS in a particular pregnancy. Many of the drug therapies used to treat BS are safe to use in pregnancy and in the breastfeeding mother. These include corticosteroids, azathioprine, calcineurin inhibitors and probably colchicine. Experience with use of biologics in pregnancy is increasing. Drugs used in the management of BS that should be avoided in women planning a pregnancy include methotrexate, mycophenolate mofetil, thalidomide, cyclophosphamide and chlorambucil.