Fetal NT-proBNP levels and their course in severe anemia during intrauterine treatment.

PURPOSE: In adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group. METHODS: We analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group. RESULTS: In the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age (R = - 74.04, T = - 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy (p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses (p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological. CONCLUSION: NT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring.

Amniotic fluid embolism-associated coagulopathy: a single-center observational study.

INTRODUCTION: Amniotic fluid embolism (AFE) continues to be a rare, enigmatic condition with high maternal mortality. It is characterized by cardiovascular compromise, loss of consciousness or other neurologic symptoms, and coagulopathy. The latter is usually treated according to existing protocols for consumptive coagulopathy. METHODS: Serial analyses of a panel of hemostaseological parameters were performed in three consecutive cases of AFE that occurred at our institution. RESULTS: All mothers and neonates survived without major sequelae. Disproportionately low levels of fibrinogen and factor five, and exorbitantly elevated D-dimers were present in all cases, whereas markers of consumptive coagulopathy, platelets and antithrombin in particular, were only slightly reduced. DISCUSSION: Our results support hyperfibrinolysis as contributing factor of AFE-associated coagulopathy. We, therefore, propose a treatment algorithm which includes early use of tranexamic acid and transfusion of red blood cells and fresh frozen plasma, adding fibrinogen if hemostasis is not readily achieved.

Self-reported physical, mental, and reproductive sequelae after treatment of abnormally invasive placenta: a single-center observational study.

OBJECTIVE: To analyze the types of treatment of abnormally invasive placenta (AIP) and to investigate the self-reported physical and mental short- and long-term sequelae. METHODS: This single-center observational study was performed between 2003 and 2017. Women with prenatal or intrapartum diagnosis of AIP were identified through the departmental database. Classification was performed according to the time of diagnosis establishment and the type of treatment. Medical complications overall and according to the type of treatment were analyzed. Data about women's perception of diagnosis, treatment, and short- and long-term sequelae were gathered by questionnaire. RESULTS: Cases were classified into four groups: prenatal diagnosis, cesarean hysterectomy (A, n = 10); prenatal diagnosis, expectant management (B, n = 19); intrapartum diagnosis, cesarean hysterectomy (C, n = 6); intrapartum diagnosis, conservative therapy (D, n = 20). Depth of invasion, total units of transfused red blood cells, and the need for reoperation differed between the treatment groups. Expectant management was successful in 94.7% of cases. Irrespective of the treatment group, 73.3% of women perceived the condition as serious or life-threatening; 30.0% utilized psychological support; and 36.7% reported persistent pain or problems. 37.5% of women after uterine preservation had another live birth, AIP recurred in 44.4% of cases. CONCLUSION: Conservative management of AIP is feasible in selected cases. The condition is perceived as life-threatening and has a lasting impact on the physical, mental, and reproductive health of those affected. This finding merits further investigation. AIP continues to be a condition with high morbidity.

Color Doppler examination for the diagnosis of subacute puerperal uterine inversion.

PURPOSE: Obstetric uterine inversion is a rare and life-threatening complication. Diagnosis is often difficult to establish, particularly in recurrent or chronic cases. METHOD: We performed color Doppler examination in addition to B-mode sonography in a case of subacute recurrent uterine inversion. RESULTS: Identification of the vessels providing uterine blood supply helped to clarify the distorted anatomy; furthermore, information about tissue viability was gained. CONCLUSION: We propose to perform color Doppler examination in all cases with suspected uterine inversion or vaginal masses of unknown origin.

Pregnancy and Autoimmune Disease.

BACKGROUND: Pregnancies in women with chronic disease are on the rise. This pertains to autoimmune diseases in particular since these tend to affect women of childbearing age. The interaction between pregnancy and autoimmune disease may increase the risk of maternal, fetal, and obstetric complications; additional care may be required. METHODS: This review is based on a selective literature search in PubMed (2015-2020). RESULTS: In women with autoimmune diseases, the course of pregnancy is highly variable. Some autoimmune diseases tend to improve during pregnancy and do not to result in any serious obstetric complications. Others may worsen during pregnancy, with deterioration of the maternal condition as well as obstetric and perinatal complications. In systemic lupus erythematosus and myasthenia gravis, placental transfer of specific autoantibodies may cause fetal or neonatal disease. CONCLUSION: The care of pregnant women with chronic diseases requires collaboration between specialists of the pertinent levels of care. A stable course of disease before conception, close interdisciplinary care, and pregnancy-compatible medication contribute to a reduction in maternal and perinatal complications.

Brain-Derived Neurotrophic Factor in Gestational Diabetes: Analysis of Maternal Serum and Cord Blood Pairs and Comparison of Dietary- and Insulin-Dependent GDM.

The Objective of our study was to investigate the influence of dietary (dGDM) and insulin-dependent (iGDM) gestational diabetes (GDM) on BDNF blood levels of corresponding maternal-neonatal pairs and compare them to pregnancies unaffected by GDM. Blood samples from 293 maternal-neonatal pairs were analyzed. Statistical analysis was performed using multiple regression analysis for association of log-transformed maternal and neonatal BDNF levels in relation to GDM, gestational age, neonatal sex, and mode of delivery. This was followed by a 2:1 matching of healthy and diabetic pairs. Maternal and neonatal BDNF levels were lowest in the iGDM group, followed by the dGDM group and healthy controls (maternal: healthy 665 ± 562 (26-2343) pg/mL vs. dGDM 593 ± 446 (25-1522) pg/mL vs. iGDM 541 ± 446 (68-2184) pg/mL; neonate: healthy 541 ± 464 (9.5-2802) pg/mL vs. dGDM 375 ± 342 (1-1491) pg/mL vs. iGDM 330 ± 326 (47-1384) pg/mL). After multiple regression analysis and additional 2:1 matching neonatal log-BDNF was significantly lower (-152.05 pg/mL, p = 0.027) in neonates of mothers with GDM compared to healthy pairs; maternal log-BDNF was also lower (-79.6 pg/mL), but did not reach significance. Our study is the first to analyze BDNF in matched maternal-neonatal pairs of GDM patients compared to a metabolically unaffected control group.

High maternal BMI and low maternal blood BDNF may determine the limit of detection of amniotic fluid BDNF throughout gestation: Analysis of mother-fetus trios and literature review.

OBJECTIVE: An increasing number of studies show the importance of brain-derived neurotrophic factor (BDNF) acting at the feto-placental interface, however, only a few studies describe BDNF levels in amniotic fluid (AF). METHODS: In this cross-sectional, prospective study, 109 maternal blood-amniotic fluid pairs (including 66 maternal blood-fetal-blood-amniotic fluid trios) were analyzed. BDNF concentrations were measured with a commercially available immunoassay. RESULTS: In 71 AF from 109 samples, AF-BDNF concentrations were below the lowest limit of Quantitation (LLoQ) of 1.19 pg/ml (group A), leaving 38 samples with measurable BDNF concentrations (group B). Patients in group A showed significantly higher maternal BMI before pregnancy (mean±SD 26.3± 6.7 (kg/m2) vs. 23.8 ±4.5 (kg/m2) p = 0.04) and lower maternal blood BDNF concentrations than the other group (mean±SD 510.6 ± 554.7 pg/ml vs. mean±SD 910.1± 690.1 pg/ml; p<0.0001). Spearman correlation showed a negative correlation between maternal BMI before pregnancy and maternal BDNF concentrations (r = -0.25, p = 0.01). CONCLUSION: Our study is the first to correlate AF-BDNF samples with the corresponding maternal and fetal blood-BDNF samples. The significant negative correlation between maternal BMI before pregnancy and maternal BDNF and AF-BDNF concentrations below the limit of detection has to be evaluated in further studies.

Early postnatal changes of circulating N-terminal-pro-B-type natriuretic peptide in neonates with congenital diaphragmatic hernia.

BACKGROUND: Severity of lung hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction are major contributors to mortality in congenital diaphragmatic hernia (CDH). Therefore, early assessment and management is important to improve outcome. NT-proBNP is an established cardiac biomarker with only limited data for early postnatal risk assessment in CDH newborns. AIMS: To investigate the correlation of NT-proBNP at birth, 6 h, 12 h, 24 h, and 48 h with PH and cardiac dysfunction and the prognostic information of NT-proBNP for the use of ECMO support or mortality. SUBJECTS: 44 CDH newborns treated at our institution (December 2014-October 2017) were prospectively enrolled. OUTCOME MEASURES: Primary clinical endpoint was either need for ECMO or death within the first 48 h (group A). Infants not receiving ECMO support were allocated to group B. Mortality was tested as secondary endpoint. RESULTS: NT-proBNP levels measured at 6 h, 12 h, 24 h and 48 h postpartum correlated significantly with PH severity following NICU admission and at 24 h, and with severity of cardiac dysfunction at birth, 24 h, 48 h and after 7 days of life. There was no difference in NT-proBNP levels between survivors and non-survivors. NT-proBNP levels were significantly higher in group A at 6 h (p = 0.007), 12 h (p = 0.036), and 24 h (p = 0.007), but not at birth (p = 0.785) or 48 h (p = 0.15) compared to group B. CONCLUSION: NT-proBNP analysis in the first 48 h of life may be useful to assess PH and cardiac dysfunction in CDH newborns and to predict the need for ECMO support.

Enteritis as initial manifestation of systemic lupus erythematosus in early pregnancy: A case report.

RATIONAL: Lupus enteritis is a rare, severe complication of systemic lupus erythematosus (SLE). We report of a patient who presented with enteritis as manifestation of new-onset SLE during the first trimester of pregnancy. PATIENTS CONCERNS: The 23-year nulliparous patient was admitted to a district hospital with abdominal pain, nausea, vomiting and bloody diarrhea at a gestational age (GA) of 10 weeks. Her symptoms improved with symptomatic treatment and she was discharged a few days later. At 15 weeks' of gestation she was readmitted. Her lab results revealed mild anemia and thrombocytopenia. Ascites, renal failure and proteinuria developed. An infectious cause was suspected, but stool samples and urine cultures were negative. Diagnostic work-up included abdominal ultrasound, gastro- and sigmoidoscopy, magnetic resonance imaging (MRI), and diagnostic laparoscopy. Ultrasound and MRI revealed dilated, fluid-filled small bowel loops, and increased colonic wall diameters. Mucosal edema and petechiae were detected by sigmoidoscopy, and histopathologic examination of the biopsies revealed erosive inflammation. Due to progressive deterioration she was transferred to our center. In addition to ascites, pleural and pericardial effusions had developed. DIAGNOSIS: Diagnosis of SLE was finally established at GA 16 after an autoimmune workup revealed positive antinuclear, anti- Sm, anti-dsDNA and anti-U1RNP antibodies. An interdisciplinary team was set up for her management. She was commenced on corticosteroids; response was only partial and necessitated addition of cyclosporine. The further clinical course was complicated by anemia, chest wall shingles, hypertension, and progressive cervical shortening. Serial ultrasound and Doppler examinations revealed notching of the uterine arteries with raised pulsatility indices and fetal growth restriction. INTERVENTION: At GA 35 abdominal pain reoccurred; a decision for delivery was taken. An apparently healthy fetus was delivered by cesarian section with good Apgar scores and pH (2100g, 9. percentile). The postoperative / postnatal course was unremarkable. OUTCOMES: New-onset SLE during pregnancy is rare, as is lupus enteritis. To our knowledge, our case is the first report of a combination of both. LESSONS: Diagnostic delay occurred a result of symptom overlap and limitations in diagnostic imaging. Interdisciplinary teamwork resulted in successful outcome for both, mother and fetus.

Pravastatin for prevention of HELLP syndrome: A case report.

RATIONALE: Pravastatin has emerged for prevention and treatment of preeclampsia; no reports are available on pravastatin and HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome. PATIENT CONCERNS: The first pregnancy necessitated termination of pregnancy at gestational age (GA) 20+5 for HELLP. Intrauterine fetal death at GA 22+5 occurred in the second pregnancy, whilst on temporizing management of HELLP. DIAGNOSES: Severe, recurrent early-onset HELLP syndrome. INTERVENTIONS: In her fourth pregnancy, pravastatin was commenced at GA 13. OUTCOMES: The course of pregnancy was uncomplicated, and a healthy, appropriate for gestational age fetus was delivered at term. LESSONS: Pravastatin may be effective in prevention of HELLP. The hepatic uptake may be of particular advantage.

Progressive cardiac dysfunction in Bethlem myopathy during pregnancy.

BACKGROUND: Bethlem myopathy is a congenital myopathy presenting with muscle weakness and joint abnormalities. Although cardiac involvement is frequent in other inherited myopathies, it has not yet been described in Bethlem myopathy. CASE: We report a case of progressive deterioration of left ventricular function during pregnancy in a patient with Bethlem myopathy. Worsening of clinical symptoms, particularly dyspnea, necessitated delivery at 36 2/7 weeks of gestation. Myocardial function recovered postpartum with improvement of clinical symptoms. CONCLUSION: Bethlem myopathy may be associated with progressive left ventricular dysfunction during pregnancy and may require early delivery.