Maternal hemodynamic changes in gestational diabetes: a prospective case-control study.

PURPOSE: The aim of the study is to compare maternal hemodynamic adaptations in gestational diabetes (GDM) versus healthy pregnancies. METHODS: A prospective case-control study was conducted, comparing 69 singleton pregnancies with GDM and 128 controls, recruited between September 2018 and April 2019 in Maternal-Fetal Medicine Unit, Careggi University Hospital, Florence, Italy. Hemodynamic assessment by UltraSonic Cardiac Output Monitor (USCOM) was performed in both groups in four gestational age intervals: 17-20 weeks (only in early GDM cases), 26-30 weeks, 32-35 weeks and 36-39 weeks. We evaluated six hemodynamic parameters comparing GDM cases versus controls: cardiac output (CO), cardiac index (CI), stroke volume (SV), total vascular resistance (TVR), inotropy index (INO) and potential to kinetic energy ratio (PKR). RESULTS: GDM group had significantly lower values of CO and SV than controls from the early third trimester (26-30 weeks) until term (p < 0.001). CI is significantly lower in GDM women already at the first evaluation (p = 0.002), whereas TVR and PKR were significantly higher in GDM (p < 0.001). GDM women showed also lower INO values than controls in all assessments. CONCLUSIONS: A hemodynamic maternal maladaptation to pregnancy can be detected in GDM women. The effect of hyperglycemia on vascular system or a poor pre-pregnancy cardiovascular (CV) reserve could explain this hemodynamic maladaptation. The abnormal CV response to pregnancy in GDM women may reveal a predisposition to develop CV disease later in life and might help in identifying patients who need a CV follow-up.

Perinatal outcomes of pregnant women with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO): a case series and literature review.

PURPOSE: Pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have a higher risk of hospitalization, admission to intensive care unit (ICU) and invasive ventilation, and of acute respiratory distress syndrome (ARDS). In case of ARDS and critical severe coronavirus disease 2019 (COVID-19), the use of extracorporeal membrane oxygenation (ECMO) is recommended when other respiratory support strategies (oxygen insufflation, non-invasive ventilation [NIV], invasive ventilation through an endotracheal tube) are insufficient. However, available data on ECMO in pregnant and postpartum women with critical COVID-19 are very limited. METHODS: A case series of three critically ill pregnant women who required ECMO support for COVID-19 in pregnancy and/or in the postpartum period. RESULTS: The first patient tested positive for COVID-19 during the second trimester, she developed ARDS and required ECMO for 38 days. She was discharged in good general conditions and a cesarean-section [CS] at term was performed for obstetric indication. The second patient developed COVID-19-related ARDS at 28 weeks of gestation. During ECMO, she experienced a precipitous vaginal delivery at 31 weeks and 6 days of gestation. She was discharged 1 month later in good general conditions. The third patient, an obese 43-year-old woman, tested positive at 38 weeks and 2 days of gestation. Because of the worsening of clinical condition, a CS was performed, and she underwent ECMO. 143 days after the CS, she died because of sepsis and multiple organ failure (MOF). Thrombosis, hemorrhage and infections were the main complications among our patients. Neonatal outcomes have been positive. CONCLUSION: ECMO should be considered a life-saving therapy for pregnant women with severe COVID-19.

Undifferentiated Connective Tissue Disease in Pregnancy: A Topic Yet to be Explored.

Undifferentiated connective tissue disease (UCTD) is characterized by signs and symptoms suggestive of a connective tissue disease (CTD), but not fulfilling criteria for a specific CTD. Although UCTD is probably the most common rheumatic disease diagnosed in pregnant women, data about disease course during pregnancy and perinatal outcomes are very limited. Compared to other CTDs, UCTD seems to have milder clinical manifestations in pregnancy. Its natural history is related to disease activity at conception. In fact, if the disease is in a state of remission or minimal activity at conception, pregnancy outcomes are generally good. On the contrary, patients who become pregnant in a moment of high disease activity and/or who have multiple antibodies positivity show an increased risk of disease flares, evolution to a definite CTD and obstetric complications, such as fetal growth restriction, preeclampsia and preterm birth. Therefore, a preconception assessment is essential in women with UCTD to evaluate maternal and fetal risks, to initiate interventions to optimize disease activity, and to adjust medications to those that are least harmful to the fetus. The aim of the present study was to review the available literature about pregnancy course, maternal and fetal outcomes and therapeutic approaches of pregnant women with UCTD.

Fetal nondiabetic-macrosomia: risk factors for pregnancy adverse outcome and comparison of two growth curves in the prediction of cesarean section.

BACKGROUND: Randomized trials reported no difference whether induction or expectant management is performed in non-diabetic women with large for gestational age babies but no tool has been validated for the prediction of high risk cases. AIM: Assessing the performance of different growth curves in the prediction of complications. METHODS: Data from 1066 consecutive non-diabetic women who delivered babies ≥4000 g were collected. Logistic regression analysis was used to analyze the impact of the maternal variables on: instrumental delivery, shoulder dystocia (SD), perineal tears, cesarean section (CS), and postpartum hemorrhage. Intergrowth21 curves and customized Gardosi's curves were compared in terms of prediction of adverse outcomes. FINDINGS: Induction of labor was performed in 23.1% cases. The rate of CS was 17%. Hemorrhage, fetal distress, and SD occurred in 2%, 1.3%, and 2.7% of cases, respectively. Induction was significantly associated with instrumental delivery (p < .001), CS (p = .001), third and fourth degree perineal tears (p = .031), and post-partum hemorrhage (p = .02). The cutoff of 90th percentile according to Intergrowth21 did not show significant performance in predicting CS, while the same cutoff according to the Gardosi curves showed an OR 1.92 (CI 1.30-2.84) (p = .0009). DISCUSSION: Gardosi curves showed a better performance in predicting the risk of CS versus Intergrowth curves. Induction is significantly associated with adverse outcome in non-diabetic women with LGA babies.

Different Gestational Diabetes Phenotypes: Which Insulin Regimen Fits Better?

Objective: Maternal characteristics and OGTT values of pregnancies complicated by gestational diabetes mellitus (GDM) were evaluated according to treatment strategies. The goal was to identify different maternal phenotypes in order to predict the appropriate treatment strategy. Methods: We conducted a retrospective study among 1,974 pregnant women followed up for GDM in a tertiary referral hospital for high-risk pregnancies (Careggi University Hospital, Florence, Italy) from 2013 to 2018. We compared nutritional therapy (NT) alone (n = 962) versus NT and insulin analogues (n = 1,012) group. Then, we focused on different insulin analogues groups: long acting (D), rapid acting (R), both D and R. We compared maternal characteristics of the three groups, detecting which factors may predict the use of rapid or long-acting insulin analogue alone versus combined therapy. Results: Among women included in the analysis, 51.3% of them needed insulin therapy for glycemic control: 61.8% D, 28.3% combined D and R, and 9.9% R alone. Age >35 years, pre-pregnancy BMI >30, family history of diabetes, previous GDM, altered fasting plasma glucose (FPG), hypothyroidism, and assisted reproductive technologies (ART) were identified as maternal variables significantly associated with the need of insulin therapy. Altered 1-h and 2-h glucose plasma glucose level at OGTT, age >35 years, and previous GDM were found as independent predicting factors for the use of combined therapy with rapid and long acting analogues for glycemic control. On the contrary, pre-pregnancy BMI <25 and normal fasting plasma glucose values at OGTT were found to be significantly associated to the use of rapid insulin analogue only. Conclusion: A number of maternal and metabolic variables may be identified at the diagnosis of GDM, in order to identify different GDM phenotypes requiring a personalized treatment for glycemic control.

Immunomodulation and preeclampsia.

Preeclampsia (PE) is an enigmatic syndrome, still with unknown aetiology and multi-factorial pathogenesis. Our understanding of the role of the immune system in PE development has undergone a transformation over the years. From a model based on the alterations in cell-mediated immunity, research moved on to a vision centred on the alteration of the humoural immunity and on the systemic involvement of the inflammatory system. The first hypothesis was classically derived from the evidence that an adequate maternal immunological response is necessary in pregnancy to allow the survival of the foetus. An abnormal response of the maternal immune system against the placenta may be the first pathogenetic step of PE, followed by a systemic inflammatory reaction. Currently available treatments for PE are mainly preventative with aspirin. Treatment aims to modulate inflammation and the immune system before their changes become established.

Preeclampsia in pregnancies complicated by systemic lupus erythematosus (SLE) nephritis: prophylactic treatment with multidisciplinary approach are important keys to prevent adverse obstetric outcomes.

INTRODUCTION: Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol. MATERIALS AND METHODS: Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean ± SD, percentage and χ2-test (significant values when p < .05). RESULTS: The prophylactic treatment (60.4% of the patients) significantly controlled the complications related to some risk factors, such as antiphospholipid antibodies (aPL) and nephritis. Preeclampsia occurred in 14.8% of patients. Patients with pregestational hypertension showed a 2.75 odds ratio of adverse events when compared to the group without chronic hypertension. The presence of proteinuria was associated with a risk of preeclampsia 2.45 times greater, as well as serum creatinine >1.2 mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine <1.2 mg/dL. A 6-month inactive disease was associated with a better outcome. A value of Estimated Glomerular Filtration Rate (eGFR) < 90 mL/min/1.73 m2 resulted in a 18.73 times greater risk of preeclampsia, intrauterine growth restriction (IUGR), and preterm delivery. DISCUSSION: A multidisciplinary approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.

Correction: Stillbirths at Term: Case Control Study of Risk Factors, Growth Status and Placental Histology.

[This corrects the article DOI: 10.1371/journal.pone.0166514.].

Human leukocyte antigen DQ2/DQ8 positivity in women with history of stillbirth.

PROBLEM: The aim of this study was to investigate the prevalence of human leukocyte antigens (HLA) DQ2 and DQ8 haplotypes, two common polymorphisms associate with celiac disease (CD), in women with previous stillbirth, but not affected by CD. METHOD OF STUDY: Women with history of unexplained term stillbirth referred to our Center for High-Risk Pregnancies for a preconception counseling, and women with previous uncomplicated pregnancies, were enrolled as cases and controls. Celiac women were excluded from the study. Genetic tests for HLA DQ2/DQ8 were performed, and patients' data were compared. RESULTS: The population included 56 women with a previous term stillbirth and 379 women with history of uncomplicated pregnancies. The prevalence of HLA-DQ2 or DQ8 positivity was significantly higher in cases than in controls (50% vs 29.5%) (P = 0.0031). Women with HLA DQ8 genotype have a significantly higher risk of stillbirth (OR: 2.84 CI: 1.1840-6.817) and in case of DQ2 genotype the OR for stillbirth was even higher (OR: 4.46 CI: 2.408-8.270). In the stillbirth group, SGA neonates were significantly more frequent in those with HLA-DQ2/DQ8 haplotypes than in those resulted negative to genetic testing (85.7% vs 42 .8%, P = 0.004). CONCLUSION: In women with history of term stillbirth, a significantly higher prevalence of HLA DQ2/DQ8 haplotypes has been found compared to women with previous uneventful pregnancies. In addition, HLA DQ2/DQ8 positivity was significantly associated with suboptimal fetal growth in intrauterine fetal death cases, as shown by an increased prevalence of SGA babies.

Stillbirths at Term: Case Control Study of Risk Factors, Growth Status and Placental Histology.

OBJECTIVE: To investigate the proportion of stillbirths at term associated with abnormal growth using customized birth weight percentiles and to compare histological placental findings both in underweight stillborn fetuses and in live births. METHODS: A retrospective case-control study of 150 singleton term stillbirths. The livebirth control groups included 586 cases of low-risk pregnancies and 153 late fetal growth restriction fetuses. Stillbirths and livebirths from low-risk pregnancies were classified using customized standards for fetal weight at birth, as adequate for gestational age (AGA; 10-90th percentile), small (SGA; <10th percentile) or large for gestational age (LGA; >90th percentile). Placental characteristics in stillbirth were compared with those from livebirths using four categories: inflammation, disruptive, obstructive and adaptive lesions. RESULTS: There was a higher rate of SGA (26% vs 6%, p<0.001) and LGA fetuses (10.6% vs 5.6%, p<0.05) in the stillbirth group. Among stillbirth fetuses, almost half of the SGA were very low birthweight (≤3°percentile) (12% vs 0.3%, p<0.001). The disruptive (7.3% vs 0.17%;p<0.001), obstructive (54.6% vs 7.5%;p<0.001) and adaptive (46.6% vs 35.8%;p<0.001) findings were significantly more common in than in livebirth-low risk. Placental characteristics of AGA and SGA stillbirth were compared with those of AGA and FGR livebirth. In stillbirths-SGA we found a higher number of disruptive (12.8% vs 0%; p<0.001), obstructive (58.9% vs 23.5%;p<0.001) and adaptive lesions (56.4% vs 49%; p 0.47) than in livebirth-FGR. CONCLUSION: The assessment of fetal weight with customized curves can identify fetuses which have not reached their genetically determined growth potential and are therefore at risk for adverse outcomes. Placental evaluation in stillbirths can reveal chronic histological signs that might be useful to clinical assessment, especially in underweight fetuses.

Inherited and acquired thrombophilias.

Thrombophilias represent an evolving story that continues to stir controversy for care providers and obstetrical patients. The predominant thrombophilic mutations include the factor V Leiden mutation, prothrombin gene mutation G20210A, methylene tetrahydrafolate reductase C667T, and deficiencies of the natural anticoagulants proteins C and S, and antithrombin. Prospective cohort studies have provided an accurate assessment of the risk of placenta-mediated complications posed by common inherited thrombophilic conditions. Acquired thrombophilic conditions consist of the antiphospholipid antibody syndrome (APAS) and hyperhomocysteinemia. Well-conducted, placebo-controlled, randomized trials have demonstrated no benefit of anticoagulation in women with recurrent pregnancy loss and inherited thrombophilia. The routine use of anticoagulation to prevent other placenta-mediated complications in the setting of inherited thrombophilia should be considered experimental until the results of adequate clinical trials are available. Heparin anticoagulation and antiplatelet therapies are the cornerstone of treatment of APAS in pregnancy.