Intravitreal anti-vascular endothelial growth factor injections in pregnancy and breastfeeding: a case series and systematic review of the literature.

INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) agents may occasionally need to be considered for sight-threatening macular pathology in pregnant and breastfeeding women. This is controversial due to the dearth of data on systemic side effects for mother and child. We aimed to expand the evidence base to inform management. METHODS: Retrospective case series of pregnant and breastfeeding women treated with intravitreal anti-VEGF injections at Oxford Eye Hospital between January 2015 and December 2022. In addition, we conducted a systematic review and combined eligible cases in a narrative synthesis. RESULTS: We treated six pregnant women with anti-VEGF for diabetic macular oedema(DMO) (n = 5) or choroidal neovascularisation (CNV) (n = 1). Four received ranibizumab whilst two (not known to be pregnant) received aflibercept. Patients known to be pregnant underwent counselling by an obstetric physician. Five pregnancies resulted in live births. Combining our cases with those previously published, treatment of 41 pregnant women (42 pregnancies) are reported. Indications for treatment included CNV (n = 28/41,68%), DMO (n = 7/41,17%) and proliferative diabetic retinopathy (n = 6/41,15%). Bevacizumab (n = 22/41,54%) and ranibizumab (n = 17/41,41%) were given more frequently than aflibercept (n = 2/41,5%). Many (n = 16/41,40%) were unaware of their pregnancy when treated. Most pregnancies resulted in live births (n = 34/42,81%). First trimester miscarriages (n = 5/42,12%) and stillbirths (n = 3/42,7%) mostly occurred in women with significant risk factors. CONCLUSION: Intravitreal anti-VEGF injections may not necessarily compromise obstetric outcomes, although clear associations cannot be drawn due to small numbers and confounders from high rates of first trimester miscarriages in general and inherently high-risk pregnancies. It may be worth considering routinely investigating pregnancy and breastfeeding status in women of childbearing age prior to each injection, as part of anti-VEGF treatment protocols.

Rhombencephalitis in Pregnancy-A Challenging Case of Probable Listeria Infection.

Rhombencephalitis refers to inflammation of the brainstem and cerebellum, and can be caused by infections, autoimmune disorders or paraneoplastic syndromes. The most common infective cause is the bacterium Listeria monocytogenes. Listeria monocytogenes is the predominant species to cause human listeriosis, and is commonly due to the ingestion of contaminated foods. Symptoms include a mild gastroenteritis, fever (often with extreme temperature variations), headache, and myalgia. In more severe cases, invasive disease may lead to bacteraemia and neurolisteriosis. Pregnant women are more susceptible to listeriosis, which is believed to be due to pregnancy-related immune modulation. Maternal-neonatal infection with adverse pregnancy outcomes include neonatal listeriosis, spontaneous miscarriage and intrauterine fetal demise. Diagnosis may be challenging due to initial nonspecific symptoms and low sensitivity and specificity of confirmatory diagnostic laboratory tests. Here, we describe a case of rhombencephalitis in pregnancy, attributed to Listeria, and review the clinical features, diagnosis and multidisciplinary management. Lastly, we describe the immunological response to Listeria monocytogenes and show in vitro pro-inflammatory effects of Listeria monocytogenes on peripheral blood mononuclear cells and placental explants.

Haemophagocytic lymphohistiocytosis in pregnancy.

Haemophagocytic lymphohistiocytosis is a life-threatening systemic inflammatory syndrome defined by persistent fever, cytopenia and multi-organ dysfunction. Primary haemophagocytic lymphohistiocytosis classically presents in childhood as a result of genetically abnormal perforin or inflammasome function, leading to the aberrant release of pro-inflammatory cytokines causing a hyperinflammatory state. Secondary haemophagocytic lymphohistiocytosis is an acquired phenomenon occurring at any age as a result of immune dysregulation to a specific trigger such as infection, haematological malignancy or autoimmune disease. Secondary haemophagocytic lymphohistiocytosis occurring in the pregnant woman represents a diagnostic challenge and carries a significant mortality. This has led to its first inclusion in the fourth Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the United Kingdom annual maternal report in 2017. This article presents an overview of haemophagocytic lymphohistiocytosis, reviews the literature on haemophagocytic lymphohistiocytosis in pregnancy, suggests diagnostic pathways and explores the safety and efficacy of existing and potential treatment strategies for haemophagocytic lymphohistiocytosis occurring during pregnancy.

Iron deficiency anaemia in pregnancy: A contemporary review.

Iron deficiency anaemia is a global health problem, which particularly affects pregnant women. Iron deficiency anaemia during pregnancy is associated with increased maternal and perinatal morbidity and mortality. Maternal iron deficiency may also be associated with neurocognitive deficits in infants. Iron requirements increase during pregnancy and are influenced by hepcidin, the master regulator of iron homeostasis. The enduring global burden of maternal anaemia suggests that currently employed iron supplementation strategies are suboptimal. Recent developments in our understanding of systemic and placental iron homeostasis may improve therapeutic effectiveness by altering the dose and frequency of oral iron. Intravenous iron appears to be a safe treatment to correct maternal anaemia rapidly but research on patient-centred outcomes and cost-effectiveness is needed. Future trials should be adequately powered to assess outcomes relevant to pregnant women.

Gastrointestinal and liver disease in pregnancy.

Gastrointestinal (GI) conditions are common in women of childbearing age. They often present before pregnancy but can arise de novo during pregnancy. The physiological changes that occur during pregnancy can influence the differential diagnosis of common GI presentations, affect the interpretation of diagnostic tests and restrict the use of diagnostic or therapeutic procedures. In this article, we summarise the clinical features, investigation and management of common GI and liver conditions that are incidental to pregnancy, and describe the specific features of pregnancy-related disorders that are less frequently encountered by general physicians. Newer developments in areas that are increasingly encountered in obstetric medical practice, including pregnancy after bariatric procedures, are also described.

Endocrine disease in pregnancy.

Endocrine disease is common in pregnancy. Most pre-existing endocrine conditions, if well controlled, have little impact on maternal or fetal morbidity. Uncontrolled endocrine conditions in pregnancy, whether poorly controlled pre-conception or newly diagnosed, are associated with a variety of adverse fetal outcomes and maternal morbidity. Also, transplacental transfer of maternal antibodies can have adverse fetal or neonatal consequences. The initial diagnosis of many conditions is hindered by the overlap of symptoms that occur in normal pregnancy and those that suggest specific endocrine pathologies, and also by the changes in reference ranges for common biochemical measurements that occur as a result of physiological changes in pregnancy. This article summarises the common endocrine disorders in pregnancy and describes how pregnancy can alter their investigation, treatment and ongoing management, as well as the potential effects on the fetus.