Sepsis: Precision-Based Medicine for Pregnancy and the Puerperium.

Sepsis contributes significantly to global morbidity and mortality, particularly in vulnerable populations. Pregnant and recently pregnant women are particularly prone to rapid progression to sepsis and septic shock, with 11% of maternal deaths worldwide being attributed to sepsis. The impact on the neonate is considerable, with 1 million neonatal deaths annually attributed to maternal infection or sepsis. Pregnancy specific physiological and immunological adaptations are likely to contribute to a greater impact of infection, but current approaches to the management of sepsis are based on those developed for the non-pregnant population. Pregnancy-specific strategies are required to optimise recognition and management of these patients. We review current knowledge of the physiology and immunology of pregnancy and propose areas of research, which may advance the development of pregnancy-specific diagnostic and therapeutic approaches to optimise the care of pregnant women and their babies.

Is the Host Viral Response and the Immunogenicity of Vaccines Altered in Pregnancy?

The intricacy of the maternal immune system arises from its ability to prevent a maternal immune response against a semi-allogenic fetus, while protecting the mother against harmful pathogens. However, these immunological adaptations may also make pregnant women vulnerable to developing adverse complications from respiratory viral infections. While the influenza and SARS pandemics support this theory, there is less certainty regarding the clinical impact of SARS-CoV-2 in pregnancy. In the current COVID-19 pandemic, vaccine development is key to public preventative strategies. Whilst most viral vaccines are able to induce a seroprotective antibody response, in some high-risk individuals this may not correlate with clinical protection. Some studies have shown that factors such as age, gender, and chronic illnesses can reduce their effectiveness and in this review, we discuss how pregnancy may affect the efficacy and immunogenicity of vaccines. We present literature to support the hypothesis that pregnant women are more susceptible to respiratory viral infections and may not respond to vaccines as effectively. In particular, we focus on the clinical implications of important respiratory viral infections such as influenza during pregnancy, and the pregnancy induced alterations in important leukocytes such as TFH, cTFH and B cells, which play an important role in generating long-lasting and high-affinity antibodies. Finally, we review how this may affect the efficacy of vaccines against influenza in pregnancy and highlight areas that require further research.

Hyponatraemia compounding pre-eclamptic toxaemia in a patient with type 1 diabetes.

We report a case of profound, symptomatic hyponatraemia in association with pre-eclamptic toxaemia (PET) in a 38-year-old nulliparous woman with type 1 diabetes mellitus. This patient developed hypertension and proteinuria at 31+6 weeks' gestation and was admitted for management of pre-eclampsia. Severe headache, visual disturbance and nausea were associated with a hyponatraemia of 115 mmol/L followed by ketoacidosis. This was reversed through fluid restriction, supplementation with 1.8%-3.0% hypertonic saline and a volume-reduced variable-rate insulin infusion. Clinical stability was achieved and she was subsequently worked up for an induction of labour for worsening pre-eclampsia. Hyponatraemia in the context of PET has been previously reported as rare. However, it has complications that may significantly compound the sequelae of severe PET. We propose that specific and focused monitoring of serum sodium levels should become common practice in the management of women with this condition to allow for timely, measured correction of abnormalities.

Changes in T Cell and Dendritic Cell Phenotype from Mid to Late Pregnancy Are Indicative of a Shift from Immune Tolerance to Immune Activation.

During pregnancy, the mother allows the immunologically distinct fetoplacental unit to develop and grow. Opinions are divided as to whether this represents a state of fetal-specific tolerance or of a generalized suppression of the maternal immune system. We hypothesized that antigen-specific T cell responses are modulated by an inhibitory T cell phenotype and modified dendritic cell (DC) phenotype in a gestation-dependent manner. We analyzed changes in surface markers of peripheral blood T cells, ex vivo antigen-specific T cell responses, indoleamine 2,3-dioxygenase (IDO) activity (kynurenine/tryptophan ratio, KTR), plasma neopterin concentration, and the in vitro expression of progesterone-induced blocking factor (PIBF) in response to peripheral blood mononuclear cell culture with progesterone. We found that mid gestation is characterized by reduced antigen-specific T cell responses associated with (1) predominance of effector memory over other T cell subsets; (2) upregulation of inhibitory markers (programmed death ligand 1); (3) heightened response to progesterone (PIBF); and (4) reduced proportions of myeloid DC and concurrent IDO activity (KTR). Conversely, antigen-specific T cell responses normalized in late pregnancy and were associated with increased markers of T cell activation (CD38, neopterin). However, these changes occur with a simultaneous upregulation of immune suppressive mechanisms including apoptosis (CD95), coinhibition (TIM-3), and immune regulation (IL-10) through the course of pregnancy. Together, our data suggest that immune tolerance dominates in the second trimester and that it is gradually reversed in the third trimester in association with immune activation as the end of pregnancy approaches.