Non-immune fetal hydrops: etiology and outcome according to gestational age at diagnosis.

OBJECTIVE: Fetal hydrops is associated with increased perinatal morbidity and mortality. The etiology and outcome of fetal hydrops may differ according to the gestational age at diagnosis. The aim of this study was to evaluate the cause, evolution and outcome of non-immune fetal hydrops (NIFH), according to the gestational age at diagnosis. METHODS: This was a retrospective cohort study of all singleton pregnancies complicated by NIFH, at the Fetal Medicine Unit at St George's University Hospital, London, UK, between 2000 and 2018. All fetuses had detailed anomaly and cardiac ultrasound scans, karyotyping and infection screening. Prenatal diagnostic and therapeutic intervention, gestational age at diagnosis and delivery, as well as pregnancy outcome, were recorded. Regression analysis was used to test for potential association between possible risk factors and perinatal mortality. RESULTS: We included 273 fetuses with NIFH. The etiology of the condition varied significantly in the three trimesters. Excluding 30 women who declined invasive testing, the cause of NIFH was defined as unknown in 62 of the remaining 243 cases (25.5%). Chromosomal aneuploidy was the most common cause of NIFH in the first trimester. It continued to be a significant etiologic factor in the second trimester, along with congenital infection. In the third trimester, the most common etiology was cardiovascular abnormality. Among the 152 (55.7%) women continuing the pregnancy, 48 (31.6%) underwent fetal intervention, including the insertion of pleuroamniotic shunts, fetal blood transfusion and thoracentesis. Fetal intervention was associated significantly with lower perinatal mortality (odds ratio (OR), 0.30 (95% CI, 0.14-0.61); P  0.05). CONCLUSIONS: An earlier gestational age at diagnosis of NIFH was associated with an increased risk of aneuploidy and worse pregnancy outcome, including a higher risk of perinatal loss. Fetal therapy was associated significantly with lower perinatal mortality. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

Weight discordance and perinatal mortality in twin pregnancy: systematic review and meta‐analysis

Objectives The primary aim of this systematic review was to explore the strength of association between birth‐weight (BW) discordance and perinatal mortality in twin pregnancy. The secondary aim was to ascertain the contribution of gestational age and growth restriction in predicting mortality in growth‐discordant twins. Methods MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched. Only studies reporting on the risk of mortality in twin pregnancies affected compared with those not affected by BW discordance were included. The primary outcomes explored were incidence of intrauterine death (IUD), neonatal death (NND) and perinatal death. Outcome was assessed separately for monochorionic (MC) and dichorionic (DC) twin pregnancies. Analyses were stratified according to BW discordance cut‐off (≥ 15%, ≥ 20%, ≥ 25% and ≥ 30%) and selected gestational characteristics, including incidence of IUD or NND before and after 34 weeks' gestation, presence of at least one small‐for‐gestational age (SGA) fetus in the twin pair and both twins being appropriate‐for‐gestational age. Risk of mortality in the larger vs smaller twin was also assessed. Meta‐analyses using individual data random‐effects logistic regression and meta‐analyses of proportion were used to analyze the data. Results Twenty‐two studies (10 877 twin pregnancies) were included in the analysis. In DC pregnancies, a higher risk of IUD, but not of NND, was observed in twins with BW discordance ≥ 15% (odds ratio (OR) 9.8, 95% CI, 3.9–29.4), ≥ 20% (OR 7.0, 95% CI, 4.15–11.8), ≥ 25% (OR 17.4, 95% CI, 8.3–36.7) and ≥ 30% (OR 22.9, 95% CI, 10.2–51.6) compared with those without weight discordance. For each cut‐off of BW discordance explored in DC pregnancies, the smaller twin was at higher risk of mortality compared with the larger one. In MC twin pregnancies, excluding cases affected by twin–twin transfusion syndrome, twins with BW discordance ≥ 20% (OR 2.8, 95% CI, 1.3–5.8) or ≥ 25% (OR 3.2, 95% CI, 1.5–6.7) were at higher risk of IUD, compared with controls. MC pregnancies with ≥ 25% weight discordance were also at increased risk of NND (OR 4.66, 95% CI, 1.8–12.4) compared with those with concordant weight. The risk of IUD was higher when considering discordant pregnancies involving at least one SGA fetus. The overall risk of mortality in MC pregnancies was similar between the smaller and larger twin, except in those with BW discordance ≥ 20%. Conclusion DC and MC twin pregnancies discordant for fetal growth are at higher risk of IUD but not of NND compared with pregnancies with concordant BW. The risk of IUD in BW‐discordant DC and MC twins is higher when at least one fetus is SGA

Safety and immunogenicity of an autoclaved Leishmania major vaccine

Objective: To test the safety and immunogenicity of two doses of autoclaved L.major (ALM) vaccine mixed with BCG.Setting: Kala-azar endemic area of eastern Sudan.Design: This was a randomised, double blind and BCG controlled phase I/II study.Subjects: Eighty healthy volunteers (forty children and forty adults) with no past history of kala-azar, no reactivity to leishmanin antigen and with a reciprocal direct agglutination test (DAT) titre o

Risk factors for abnormally invasive placenta: a systematic review and meta-analysis.

Purpose of the article. To explore the strength of association between different maternal and pregnancy characteristics and the occurrence of abnormally invasive placenta (AIP). MATERIALS AND METHODS: Pubmed, Embase, CINAHL databases were searched. The risk factors for AIP explored were: obesity, age > 35 years, smoking before or during pregnancy, placenta previa, prior cesarean section (CS), placenta previa and prior CS, prior uterine surgery, abortion and uterine curettage, in vitro fertilization (IVF) pregnancy and interval between a previous CS and a subsequent pregnancy. Random-effect head-to-head meta-analyses were used to analyze the data. RESULTS: Forty-six were included in the systematic review. Maternal obesity (Odd ratio, OR: 1.4, 95% CI 1.0-1.8), advanced maternal age (OR: 3.1, 95% CI 1.4-7.0) and parity (OR: 2.5, 95% CI 1.7-3.6), but not smoking were associated with a higher risk of AIP. The presence of placenta previa in women with at least a prior CS was associated with a higher risk of AIP compared to controls, with an OR of 12.0, 95% CI 1.6-88.0. Furthermore, the risk of AIP increased with the number of prior CS (OR of 2.6, 95% CI 1.6-4.4 and 5.4, 95% CI 1.7-17.4 for two and three prior CS respectively). Finally, IVF pregnancies were associated with a high risk of AIP, with an OR of 2.8 (95% CI 1.2-6.8). CONCLUSION: A prior CS and placenta previa are among the strongest risk factors for the occurrence of AIP

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Risk of fetal loss following amniocentesis or chorionic villus sampling in twin pregnancy: systematic review and meta‐analysis

Objective To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy. Methods MEDLINE, EMBASE and Cochrane databases were searched for studies reporting procedure‐related complications following amniocentesis or CVS in twin pregnancy. The primary outcome was the rate of procedure‐related fetal loss. The secondary outcomes were fetal loss occurring before 24 weeks of gestation and fetal loss occurring within 4 weeks after the procedure. Head‐to‐head meta‐analyses were used to compare directly each outcome, between women undergoing amniocentesis and those not undergoing amniocentesis and between women undergoing CVS and those not undergoing CVS, and to compute pooled risk differences (RD) between women exposed and those not exposed to each invasive procedure. Additionally, meta‐analyses of proportions were used to estimate the pooled rates of each of the three outcomes in women undergoing amniocentesis or CVS and in controls. Results Sixteen studies (3419 twin pregnancies undergoing and 2517 not undergoing an invasive procedure) were included. Head‐to‐head meta‐analyses comparing directly twin pregnancies undergoing and those not undergoing amniocentesis showed a higher risk for overall fetal loss in those undergoing amniocentesis (odds ratio (OR), 1.46 (P = 0.04); RD, 0.013 (P = 0.04)), while there was no difference in the risk of either fetal loss before 24 weeks of gestation (OR, 1.59 (P = 0.06); RD, 0.010 (P = 0.11)) or fetal loss within 4 weeks after the procedure (OR, 1.38 (P = 0.3); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4–3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9–4.6%) in those not undergoing amniocentesis. Head‐to‐head meta‐analyses directly comparing twin pregnancies undergoing and those not undergoing CVS showed no significant difference in either overall fetal loss (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)) or fetal loss before 24 weeks of gestation (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0–6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3–4.2%) in those not undergoing CVS. Conclusion The risk of fetal loss following amniocentesis and CVS in twins is lower than reported previously and the rate of fetal loss before 24 weeks of gestation, or within 4 weeks after the procedure, did not differ from the background risk in twin pregnancy not undergoing invasive prenatal testing. These data can guide prenatal counseling for twin pregnancies undergoing invasive procedures

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Outcome of twin–twin transfusion syndrome according to Quintero stage of disease: systematic review and meta‐analysis

Objectives To report the outcome of pregnancies complicated by twin–twin transfusion syndrome (TTTS) according to Quintero stage. Methods MEDLINE, EMBASE and CINAHL databases were searched for studies reporting the outcome of pregnancies complicated by TTTS stratified according to Quintero stage (I–V). The primary outcome was fetal survival rate according to Quintero stage. Secondary outcomes were gestational age at birth, preterm birth (PTB) before 34, 32 and 28 weeks' gestation and neonatal morbidity. Outcomes are reported according to the different management options (expectant management, laser therapy or amnioreduction) for pregnancies with Stage‐I TTTS. Only cases treated with laser therapy were considered for those with Stages‐II–IV TTTS and only cases managed expectantly were considered for those with Stage‐V TTTS. Random‐effects head‐to‐head meta‐analysis was used to analyze the extracted data. Results Twenty‐six studies (2699 twin pregnancies) were included. Overall, 610 (22.6%) pregnancies were diagnosed with Quintero stage‐I TTTS, 692 (25.6%) were Stage II, 1146 (42.5%) were Stage III, 247 (9.2%) were Stage IV and four (0.1%) were Stage V. Survival of at least one twin occurred in 86.9% (95% CI, 84.0–89.7%) (456/552) of pregnancies with Stage‐I, in 85% (95% CI, 79.1–90.1%) (514/590) of those with Stage‐II, in 81.5% (95% CI, 76.6–86.0%) (875/1040) of those with Stage‐III, in 82.8% (95% CI, 73.6–90.4%) (172/205) of those with Stage‐IV and in 54.6% (95% CI, 24.8–82.6%) (5/9) of those with Stage‐V TTTS. The rate of a pregnancy with no survivor was 11.8% (95% CI, 8.4–15.8%) (69/564) in those with Stage‐I, 15.0% (95% CI, 9.9–20.9%) (76/590) in those with Stage‐II, 18.6% (95% CI, 14.2–23.4%) (165/1040) in those with Stage‐III, 17.2% (95% CI, 9.6–26.4%) (33/205) in those with Stage‐IV and in 45.4% (95% CI, 17.4–75.2%) (4/9) in those with Stage‐V TTTS. Gestational age at birth was similar in pregnancies with Stages‐I–III TTTS, and gradually decreased in those with Stages‐IV and ‐V TTTS. Overall, the incidence of PTB and neonatal morbidity increased as the severity of TTTS increased, but data on these two outcomes were limited by the small sample size of the included studies. When stratifying the analysis of pregnancies with Stage‐I TTTS according to the type of intervention, the rate of fetal survival of at least one twin was 84.9% (95% CI, 70.4–95.1%) (94/112) in cases managed expectantly, 86.7% (95% CI, 82.6–90.4%) (249/285) in those undergoing laser therapy and 92.2% (95% CI, 84.2–97.6%) (56/60) in those after amnioreduction, while the rate of double survival was 67.9% (95% CI, 57.0–77.9%) (73/108), 69.7% (95% CI, 61.6–77.1%) (203/285) and 80.8% (95% CI, 62.0–94.2%) (49/60), respectively. Conclusions Overall survival in monochorionic diamniotic pregnancies affected by TTTS is higher for earlier Quintero stages (I and II), but fetal survival rates are moderately high even in those with Stage‐III or ‐IV TTTS when treated with laser therapy. Gestational age at birth was similar in pregnancies with Stages‐I–III TTTS, and gradually decreased in those with Stages‐IV and ‐V TTTS treated with laser and expectant management, respectively. In pregnancies affected by Stage‐I TTTS, amnioreduction was associated with slightly higher survival compared with laser therapy and expectant management, although these findings may be confirmed only by future head‐to‐head randomized trials