Use of insulin degludec in pregnancy: two case reports and a literature review

Abstract As of now, insulin Degludec has no indication for use in pregnancy, because of the lack of studies that prove its safety for foetus. However it isn't infrequent that some women conceive while treating with insulin Degludec. So, before deciding to change the type of insulin therapy during pregnancy, an evaluation of the risk associated to a possible temporary worsening of glycaemic control, due to that insulin replacement, is needed. Referring to case series reported in the scientific literature could provide a support when a clinical decision need to be taken. We report two cases of women affected by type 1 diabetes who had unplanned pregnancies during treatment with insulin Degludec. In order to avoid the risk of a possible worsening of glycaemic control due to insulin switch, we decided to continue the treatment with Degludec during their pregnancies, after obtaining the patients' written informed consent. Daily insulin requirement gradually increased for both women pregnancy progressed, and glycated haemoglobin (HbA1c) values improved from the first observation to delivery: 55 mmol/mol (7.2%) at 9 weeks to 47 mmol/mol (6.5%) at 36 weeks, in Patient 1 (P1); 44 mmol/mol (6.2%) at 8 weeks to 33 mmol/mol (5.2%) at 36 weeks, in Patient 2 (P2). P1 delivered at week 37 with a caesarean section due to failed induction. The newborn, a girl of 3398 g at birth, developed neonatal hypoglycaemia and respiratory distress (Apgar 6-6). Six days after birth she underwent colectomy because of necrotizing enterocolitis and was finally diagnosed with atypical cystic fibrosis. P2 gave birth to a healthy girl (weight 2745g at birth, Apgar 7-9) at 37 weeks, undergoing a caesarean section for maternal cervical dystocia, without neonatal complications. Our experience provides additional evidence on the safety of insulin Degludec in pregnancy without any maternal or neonatal outcome suggesting its toxicity

Maternal and foetal placental vascular malperfusion in pregnancies with anti-phospholipid antibodies

The objective of the study was to evaluate the rates of pathological placental lesions among pregnant subjects positive for aPL antibodies

The impact of various entities of antiphospholipid antibodies positivity on adverse pregnancy outcome. An epidemiological perspective

The aim of the study was to evaluate the rate of obstetric complications and the burden of obstetric outcomes in antiphospholipid syndrome (APS), non-criteria APS and asymptomatic antiphospholipid antibodies (aPL) carriers. From 2013-2018, 163 pregnant subjects with aPL antibodies and 785 controls were enrolled. Penalized logistic regression was used to compare obstetric complications. Cases included 62 complete APS (38 %), 48 non-criteria APS (29.4 %) and 53 (32.5 %) asymptomatic aPL-carriers. Connective tissue diseases (CTDs) were diagnosed in 31.3 % of cases. The rate of high-risk aPL profile was higher (p < .01) in APS (67.7 %) compared to non-criteria (14.6 %) and aPL-carriers (9.4 %). Double/triple positivity was 33.9 % (p < .05 compared to non-criteria and aPL-carriers) in APS, 10.4 % in non-criteria and 9.4 % in aPL-carriers. The rate of adverse pregnancy outcomes were 5.6 % in controls, 41.9 % (adj.OR = 6.95 %CI = 2.7-13.5) in APS, 25 % (adj.OR = 4.4,95 %CI = 2-9.4) in non-criteria and 28.3 % (OR = 4.95 %CI = 1.8-8.8) in aPL-carriers. CTDs were independently associated with an increased risk of adverse obstetric outcomes (OR = 2.8,95 %CI = 1.36-5.89). The attributable fraction (AF) of adverse obstetric events was higher among low-risk antibodies compared to high-risk (AF = 0.27,95 %CI = 0.22-0.31 vs AF = 0.16,95 %CI = 0.16-0.2,p < .01) and among single positivity compared to double/triple positivity (AF = 0.32,95 %CI = 0.26-0.37 vs AF = 0.11,95 %CI = 0.09-0.13,p < .01) suggesting that low-risk subjects are responsible for a high burden of obstetric complications

Placental pathologic features in thyroid autoimmunity

Introduction: Data on placental pathologic features associated with thyreoperoxidase antibodies (TPO Ab) and/or hypothyroidism are limited. The objective of the study was to analyze placental pathologic features of women with TPO Ab positivity.Methods: Prospective case-control observational study of pregnancy outcome among women screened for TPO Ab positivity and/or isolated hypothyroidism (TSH>4mU/L) during the first trimester of pregnancy. Placenta pathologic findings were recorded according to standard classification.Results: The overall rates of TPO Ab positivity and isolated hypothyroidism with negative TPO Ab were 9.6% (86/899) and 2.7% (24/899), respectively. Among TPO Ab positive cases, 77.9% (67/86) and 22.1% (19/86) had TSH >= 2.5mU/L or = 2.5mU/L. The rates of fetal growth restriction (FGR)/small for gestational age (SGA) (20/67 versus 8/110, Adjusted Odds Ratio (AdjOR) = 10.8,95%CI = 2.7-44), placental pathological features suggesting decidual vasculopathy (37/67 versus 27/110, AdjOR = 2.7,95%CI = 1.1-6.8) or severe maternal vascular malperfusion (MVM) (22/67 versus 9/110, AdjOR = 5.8,95%CI = 1.6-20.1) were higher among cases with TSH >= 2.5mU/L than in controls. Similar results were obtained comparing overall TPO Ab positive subjects to controls. The increased risk of defective placentation and FGR associated with TPO Ab was independent of simultaneous presence of antinuclear antibodies (ANA) and TSH concentration.Discussion: First trimester TPO Ab positivity was associated with increased rates of abnormal uterine artery Doppler PI and placental features of MVM. This association was independent of TSH concentration and presence of ANA