Perinatal outcome of pregnancy complicated by twin anemia-polycythemia sequence: systematic review and meta-analysis.

OBJECTIVE: To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted. METHODS: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin-twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6-7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4-13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6-5.7%) and 9.2% (95% CI, 6.6-12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6-33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4-51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5-5.7%) and 11.1% (95% CI, 6.2-17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2-93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3-100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3-17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2-17.6%), 12.1% (95% CI, 7.7-17.3%) and 7.6% (95% CI, 1.3-18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6-43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7-35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3-60.5%) of those in the IUT group and 23.3% (95% CI, 10.5-39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8-94.8%), 73.4% (95% CI, 48.1-92.3%), 100% (95% CI, 76.5-100%) and 100% (95% CI, 39.8-100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively. CONCLUSIONS: The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Determinants of Neonatal Jaundice among Neonates Admitted to Neonatal Intensive Care Unit in Public General Hospitals of Central Zone, Tigray, Northern Ethiopia, 2019: a Case-Control Study.

BACKGROUND: Neonatal jaundice is common a clinical problem worldwide. Globally, every year, about 1.1 million babies develop severe hyperbilirubinemia with or without bilirubin encephalopathy and the vast majority reside in sub-Saharan Africa and South Asia. Strategies and information on determinants of neonatal jaundice in sub-Saharan Africa are limited. So, investigating determinant factors of neonatal jaundice has paramount importance in mitigating jaundice-related neonatal morbidity and mortality. Methodology. Hospital-based unmatched case-control study was conducted by reviewing medical charts of 272 neonates in public general hospitals of the central zone of Tigray, northern Ethiopia. The sample size was calculated using Epi Info version 7.2.2.12, and participants were selected using a simple random sampling technique. One year medical record documents were included in the study. Data were collected through a data extraction format looking on the cards. Data were entered to the EpiData Manager version 4.4.2.1 and exported to SPSS version 20 for analysis. Descriptive and multivariate analysis was performed. Binary logistic regression was used to test the association between independent and dependent variables. Variables at p value less than 0.25 in bivariate analysis were entered to a multivariable analysis to identify the determinant factors of jaundice. The level of significance was declared at p value <0.05. RESULTS: A total of 272 neonatal medical charts were included. Obstetric complication (AOR: 5.77; 95% CI: 1.85-17.98), low birth weight (AOR: 4.27; 95% CI:1.58-11.56), birth asphyxia (AOR: 4.83; 95% CI: 1.617-14.4), RH-incompatibility (AOR: 5.45; 95% CI: 1.58-18.74), breastfeeding (AOR: 6.11; 95% CI: 1.71-21.90) and polycythemia (AOR: 7.32; 95% CI: 2.51-21.311) were the determinants of neonatal jaundice. CONCLUSION: Obstetric complication, low birth weight, birth asphyxia, RH-incompatibility, breastfeeding, and polycythemia were among the determinants of neonatal jaundice. Hence, early prevention and timely treatment of neonatal jaundice are important since it was a cause of long-term complication and death in neonates.

The utility of preoperative level of erythrocytosis in the prediction of postoperative blood loss and 30-day mortality in patients with tetralogy of fallot.

BACKGROUND: Postoperative major bleeding is a relatively common complication of patients undergoing corrective surgery of tetralogy of Fallot (TOF). Life-threatening blood losses can lead to aggressive transfusions or reoperation. Little is known about the risk factors associated with a bleeding tendency in TOF patients. This study aimed to establish predictive models for postoperative blood loss and mortality in TOF patients. METHODS: We conducted a retrospective observational study involving patients with TOF who were posted for corrective cardiac surgery in a single hospital between 2010 and 2015. Hospital records including sociodemographic, pre- and intra-operative characteristics were extracted. Postoperative blood loss (within 24 and 48 h) and 30-day mortality were the primary and secondary outcomes, respectively. Multivariate linear and logistic regression models were used to identify determinants of outcomes. RESULTS: A total of 60 patients were included in this study. The median age was 1 year (interquartile range = 0.62-5) and the male to female ratio of 1.7:1. Mean postoperative blood loss within 24 h was 283 ± 212 mL. In multivariate linear regression, preoperative hematocrit (ß = 6.63, P = 0.042) and duration of intraoperative oxygenator with CPB (ß = 5.16, P = 0.025) were significantly correlated with postoperative blood loss within 24 h. After adjusting for sociodemographic, intra- and post-operative characteristics, preoperative hematocrit (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.01-1.21), and postoperative red blood cell transfusions (OR = 3.88, 95% CI = 1.16-12.9) showed statistically significant association with 30-day mortality. The area under the receiver operating characteristic curve of the multivariable model was 0.863. CONCLUSIONS: Preoperative levels of erythrocytosis appear to predict postoperative blood loss and short-term mortality in TOF patients undergoing corrective surgery.

Raised haematocrit concentration and the risk of death and vascular complications after major surgery.

BACKGROUND: Preoperative anaemia is associated with adverse postoperative outcomes. Data on raised preoperative haematocrit concentration are limited. This study aimed to evaluate the effect of raised haematocrit on 30-day postoperative mortality and vascular events in patients undergoing major surgery. METHODS: This was a cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Thirty-day mortality and vascular events, demographics and perioperative risk factors were obtained for adults undergoing major surgery. The adjusted effect of raised (over 0·50) compared with normal (0·41-0·50, American Medical Association reference range) preoperative haematocrit concentration on postoperative outcomes was assessed. Separate sex-specific analyses were also conducted, using haematocrit concentration thresholds commonly used in the diagnosis and management of apparent or absolute erythrocytosis. RESULTS: Some 3961 (2·0 per cent) of 197 469 patients had a raised haematocrit concentration before surgery. After adjustment, the 30-day postoperative mortality rate was higher in patients with raised haematocrit than in those without (odds ratio (OR) 2·23, 95 per cent confidence interval 1·77 to 2·80). Thirty-day rates of deep vein thrombosis (OR 1·95, 1·44 to 2·64) and pulmonary embolism (OR 1·79, 1·17 to 2·73), but not myocardial infarction or stroke, were also higher in patients with a raised haematocrit concentration. The effect on mortality was noted beyond the haematocrit thresholds of 0·48 in women and 0·52 in men; the effect estimates were considerably higher for values exceeding 0·54. Values between 0·41 and 0·45 were not associated with increased mortality risk. Similar observations were noted for venous thrombosis, although with apparent sex differences. CONCLUSION: A raised haematocrit concentration was associated with an increased risk of 30-day mortality and venous thrombosis following major surgery.

Hemoglobin levels above anemia thresholds are maximally predictive for long-term survival in COPD with chronic respiratory failure.

BACKGROUND: In patients with COPD, chronic anemia is known as an unfavorable prognostic factor. Whether the association between hemoglobin (Hb) levels and long-term survival is restricted to anemia or extends to higher Hb levels has not yet been systematically assessed. METHODS: We determined Hb levels in 309 subjects with COPD and chronic respiratory failure prior to initiation of noninvasive ventilation, accounting for confounders that might affect Hb. Subjects were categorized as anemic (Hb < 12 g/dL in females, Hb < 13 g/dL in males), polycythemic (Hb ≥ 15 g/dL in females, Hb ≥ 17 g/dL in males), or normocythemic. In addition, percentiles of Hb values were analyzed with regard to mortality from any cause. RESULTS: Two-hundred seven subjects (67.0%) showed normal Hb levels, 46 (14.9%) had anemia, and 56 (18.1%) had polycythemia. Polycythemic subjects showed a higher survival rate than anemic (P = .01) and normocythemic subjects (P = .043). In a univariate Cox hazards model, Hb was associated with long-term survival (hazard ratio 0.855; 95% CI 0.783-0.934, P < .001). The 58th percentiles of Hb (14.3 g/dL in females, 15.1 g/dL in males) yielded the highest discriminative value for predicting survival (hazard ratio 0.463, 95% CI 0.324-0.660, P < .001). In the multivariate analysis this cutoff was an independent predictor for survival (hazard ratio 0.627, 95% CI 0.414-0.949, P = .03), in addition to age and body mass index. CONCLUSIONS: In subjects with COPD and chronic respiratory failure undergoing treatment with noninvasive ventilation and LTOT, high Hb levels are associated with better long-term survival. The optimal cutoff level for prediction was above the established threshold defining anemia. Thus, predicting survival only on the basis of anemia does not fully utilize the prognostic potential of Hb values in COPD.

Hematocrit level as a marker of outcome in ST-segment elevation myocardial infarction.

Anemia is a well-known predictor of a poor outcome in patients with ST-segment elevation myocardial infarction (STEMI). In contrast, data relating erythrocytosis to clinical outcomes in patients with STEMI are limited. Because erythrocytosis predisposes to a prothrombotic state, we hypothesized it would be associated with an increased risk of thrombotic complications in patients with STEMI undergoing primary percutaneous coronary intervention. We studied 1,042 consecutive patients with STEMI who underwent primary percutaneous coronary intervention and were a part of our primary percutaneous coronary intervention registry from 2001 to 2007. Patients with cardiogenic shock and late arrival were excluded. Patients were allocated into 3 groups according to their baseline hematocrit: anemia (<36% for women and <39% for men), normal, erythrocytosis (>46% for women and >47% for men). The clinical outcomes were assessed at 1, 6, and 12 months. The patients with anemia had the greatest clinical risk profile. Patients with erythrocytosis had a lower risk profile than the other 2 groups, except for greater rates of smoking. The mortality rates were greatest among the patients with anemia, followed by the patients with erythrocytosis, who in turn had greater short-term mortality than patients with normal hematocrit. Multivariate analysis, which included patients with erythrocytosis and those with normal hematocrit (excluding the patients with anemia), revealed that erythrocytosis was associated with an odds ratio of 4.3 (95% confidence interval 1.4 to 13, p = 0.01) for 1-month mortality. In conclusion, although not as strong a predictor of mortality as anemia, erythrocytosis might be associated with increased short-term mortality compared to a normal hematocrit. The measurement of hematocrit can be used as a useful prognostic marker in patients with STEMI.

Transitory increase in middle cerebral artery peak systolic velocity of recipient twins after fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

OBJECTIVE: It was the aim of this study to elucidate the clinical features of recipient twins with increased middle cerebral artery peak systolic velocity (MCA-PSV) after fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome. METHODS: Serial Doppler velocimetry of the MCA was performed in 30 recipient twins before and after FLP. Clinical data and perinatal outcome were compared between cases with and without increased MCA-PSV. RESULTS: Increased MCA-PSV was observed in 7 recipients (23.3%) within 14 days after FLP. MCA-PSV gradually decreased to <1.5 multiples of median in 6 recipients; however, 1 patient resulted in fetal demise subsequent to the demise of the co-twin. The incidences of fetal and neonatal demise and neurological morbidity were similar. No recipient was diagnosed as anemic at birth. CONCLUSIONS: The increase in MCA-PSV in recipients following FLP appeared to be generally transitory; this differs from twin anemia-polycythemia sequence.

A prospective analysis of thrombotic events in the European collaboration study on low-dose aspirin in polycythemia (ECLAP).

BACKGROUND: - The clinical course of polycythemia vera (PV) is often complicated by arterial and venous thrombosis. Current information on these vascular complications derives from very few prospective clinical trials and several retrospective studies. The purpose of this analysis is to report the incidence, clinical features and risk factors for thrombosis in a large number of patients prospectively followed in a multicountry European study. METHODS: - The European collaboration on low-dose aspirin in polycythemia vera (ECLAP) study is a multicenter project aimed at describing the natural history of PV. Overall, 1630 PV patients (57% males, median age at recruitment 65 years) were enrolled in the study. Five hundred and eighteen (32%) of these patients are entered into a parallel, double-blind, placebo-controlled, randomized clinical trial aimed at assessing the efficacy and safety of low-dose aspirin. The remaining 1112 (68%) are entered into an ongoing, observational, prospective, cohort study. The mean follow-up duration was 2.7 years (range 0-5.3). FINDINGS: - The cumulative incidence rate of cardiovascular events (i.e. cardiovascular death and non-fatal thrombotic events) was 5.5 events/100 persons per year. Thrombosis was the main cause of death. Age greater than 65 years and positive history of thrombosis were the two most important predictors of cardiovascular events. Smoking, hypertension and congestive heart failure were other significant risk factors for thrombosis. Platelet counts and myelosuppressive drugs were not associated with the risk of cardiovascular events. Antiplatelet therapy was the only variable associated with a lower risk of thrombosis. CONCLUSION: - Cardiovascular events remain a major cause of mortality and morbidity in PV but the thrombotic risk seems to be more related to the patients' characteristics (age, previous thrombosis, cardiovascular risk factors) than to the disease itself. Thus, control of red cell mass and antithrombotic therapy appear to be effective treatments in limiting the risk of thrombosis.

Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors.

Adaptation to hypoxia is critical for survival and regulates multiple processes, including erythropoiesis and vasculogenesis. Chuvash polycythemia is a hypoxia-sensing disorder characterized by homozygous mutation (598C>T) of von Hippel-Lindau gene (VHL), a negative regulator of hypoxia sensing. Although endemic to the Chuvash population of Russia, this mutation occurs worldwide and originates from a single ancient event. That VHL 598C>T homozygosity causes elevated normoxic levels of the transcription factor hypoxia inducible factor-1alpha (HIF-1alpha), serum erythropoietin and hemoglobin is known, but the disease phenotype has not been documented in a controlled manner. In this matched cohort study, VHL 598C>T homozygosity was associated with vertebral hemangiomas, varicose veins, lower blood pressures, and elevated serum vascular endothelial growth factor (VEGF) concentrations (P <.0005), as well as premature mortality related to cerebral vascular events and peripheral thrombosis. Spinocerebellar hemangioblastomas, renal carcinomas, and pheochromocytomas typical of classical VHL syndrome were not found, suggesting that overexpression of HIF-1alpha and VEGF is not sufficient for tumorigenesis. Although hemoglobin-adjusted serum erythropoietin concentrations were approximately 10-fold higher in VHL 598C>T homozygotes than in controls, erythropoietin response to hypoxia was identical. Thus, Chuvash polycythemia is a distinct VHL syndrome manifested by thrombosis, vascular abnormalities, and intact hypoxic regulation despite increased basal expression of hypoxia-regulated genes.

[Treatment of polycythemia with 32P with or without hydroxyurea maintenance therapy. Preliminary results in 237 elderly and high vascular risk subjects studied since 1980]. / Traitement des polyglobulies par 32P avec ou sans traitement d'entretien par hydroxyurée. Résultats préliminaires chez 237 sujets âgés ou à haut risque vasculaire étudiés depuis 1980.

Between 1980 and 1992, 237 polycythaemic patients aged 65 or more, or with high vascular risk factors were treated with 32P according to a protocol using, or not, maintenance therapy with low-dose hydroxy-urea (500 mg/day). The present follow-up covers 1448 years/patient. Maintenance therapy was seldom discontinued because of blood toxicity or gastrointestinal intolerance, but it was stopped in 20 percent of the cases because monitoring was difficult in very old patients. Maintenance therapy reduced the mean annual 32P dose by at least 50 percent. However, the actual risk of malignant blood diseases (myelodysplasia, acute leukaemia, lymphoma) was similar in the two arms of the protocol: 14 percent at the 10th year. Compared with the French population of the same age-groups, there was no excess of epithelial cancers in both arms. Maintenance therapy did not control platelet counts perfectly. The risk of severe vascular events was identical in both arms; probably no higher than expected at that age and significantly lower than in previously published data. The actuarial survival curves in both groups showed a 50 percent survival of about 11 years, i.e. very near to that of the reference French population (12.5 years) of similar sex and age.

Morbidity and mortality in pseudopolycythaemia.

A follow-up of 35 patients with pseudopolycythaemia showed that symptoms, high packed-cell volumes, and low plasma volumes persisted in most patients. The death-rate in these patients was six times greater than expected. Patients with pseudopolycythaemia are often regarded as having a good prognosis; however, this view should be revised in the light of these findings.