Cervical length at mid gestation for the screening of pre-term birth in twin pregnancies

Objective Short cervical length (CL) in mid-gestation is considered predictive of spontaneous preterm birth (PTB). The medical literature suggests 20 mm as the cut-off for high risk in twin pregnancies. Our objective was to assess the predictive value of CL for spontaneous PTB < 32 weeks' gestation in twin pregnancies and to calculate the cut-off point with the best sensitivity and specificity. Methods This was a single-center retrospective cohort study of women in whom CL had been measured by transvaginal ultrasound at 18–23 weeks' gestation. Pregnancies complicated by twin-to-twin transfusion syndrome, those requiring intrauterine therapy or those with indicated PTB were excluded. The predictive value of CL for PTB < 32 weeks was assessed. The distribution of CL measurements and the optimal cut-off in patients with PTB were calculated and logistic regression analysis was performed to assess the association between pregnancy characteristics and PTB. Results A total of 940 twin pregnancies were included. CL showed an area under the receiver–operating characteristics curve of 0.65 (95% CI, 0.58–0.71) for the prediction of PTB < 32 weeks. The optimal cut-off value for predicting PTB was 36 mm (sensitivity, 64.1%; specificity, 62.8%; positive predictive value, 13.5%; negative predictive value, 95.1%; accuracy, 62.9%). The relative risk of PTB with CL ≤ 36 mm was 2.35 (95% CI, 1.53–3.60; P < 0.001). After adjusting for confounders in logistic regression analysis, only CL (adjusted odds ratio (aOR), 0.94 (95% CI, 0.90–0.99); P = 0.03), and not monochorionicity (aOR 4.14 (95% CI, 0.89–19.25); P = 0.07), was independently associated with PTB. More than one-third (36%) of PTB cases delivering < 32 weeks had a normal CL in mid-gestation. This proportion rose to 85% when considering the 20-mm cut-off suggested by the medical literature. Conclusions This study shows that, despite the weak independent association, CL assessed in mid-gestation is a poor predictor of PTB < 32 weeks' gestation in asymptomatic twin pregnancies

Inter-twin discrepancy in middle cerebral artery peak systolic velocity and pregnancy outcome in monochorionic diamniotic twin pregnancies

OBJECTIVES: To assess the role of inter-twin discrepancy in middle cerebral artery peak systolic velocity (MCA-PSV) for the prediction of late selective intrauterine growth restriction (sIUGR) at birth and birth-weight (BW) discrepancy >25% (BW-25) in otherwise uncomplicated monochorionic diamniotic (MCDA) twin pregnancies. METHODS: Cohort study on all MCDA pregnancies followed in a tertiary fetal medicine unit between 2008-2012.EXCLUSION CRITERIA:referral after first trimester, abnormal karyotype, structural anomalies, twin to twin transfusion syndrome, twin anemia-polycythemia sequence and sIUGR detected before 28 weeks. MCA-PSV values of both twins measured in the second trimester (18-24 weeks) and early third trimester (26-32 weeks) were converted in multiples of the median (MoM). sIUGR was defined as birth weight <5th centile. The relationship between MCA-PSV discrepancy, sIUGR and BW-25 was assessed by logistic regression analysis. Receiver operating characteristic (ROC) curves were used to ascertain the predictive value of MCA-PSV discrepancy for such complications. RESULTS: 136 MCDA twin pregnancies were included in the analysis. Thirty (22.1%) were complicated with sIUGR at birth; 12 (8.8%) were complicated with BW-25. Logistic regression analysis identified MCA-PSV discrepancy as an independent predictor for sIUGR. ROC curves identified third trimester MCA-PSV discrepancy as the best predictor for both sIUGR (AUC 0.73; 95%Cl 0.62-0.85; p < 0.001) and BW-25 (AUC 0,79; 95% Cl 0,65 - 0,93). The optimal cut off point was 0.30 MoM (sensitivity 0.67, specificity 0.76 for sIUGR; sensitivity 0.83, specificity 0.72 for BW-25). CONCLUSION: In MCDA twin pregnancies, MCA-PSV discrepancy is related to both sIUGR at birth and BW discrepancy.

Outcome of monochorionic diamniotic twin pregnancies followed at a single center

OBJECTIVE: We aim to evaluate the outcome of a cohort of monochorionic diamniotic twin pregnancies followed from the first trimester onwards at a single center. METHOD: This was a retrospective analysis of prospectively collected data from a series of 300 monochorionic diamniotic twin pregnancies referred to our twin clinic between 2001 and 2012. Pregnancies were followed from the first trimester and fortnightly after 16 weeks of gestation. Data on pregnancy and neonatal outcome were analyzed. RESULTS: There were two surviving infants in 259/300 (86.4%) pregnancies, one survivor in 22/300 (7.3%) and no survivors in 19/300 (6.3%) with an overall mortality of 60/600 (10%). Twin-twin transfusion syndrome was diagnosed in 33 cases (11%), isolated intertwin weight discordance ≥ 25% in 35 (11.6%) and major congenital structural anomalies in ten (3.3%). After 32 weeks, the prospective risk of spontaneous fetal intrauterine death was one in 248 (0.4%) per pregnancy. CONCLUSIONS: Despite specific prenatal fetal monitoring and management, monochorionic diamniotic twin pregnancies have still to be considered at high risk of mortality, although the prospective risk of intrauterine death after 32 weeks is low. Twin-twin transfusion syndrome and congenital anomalies were the main risk factors for mortalit

Molecular Basis of Resistance to Fusarium Ear Rot in Maize

The impact of climate change has been identified as an emerging issue for food security and safety, and the increased incidence of mycotoxin contamination in maize over the last two decades is considered a potential emerging hazard. Disease control by chemical and agronomic approaches is often ineffective and increases the cost of production; for this reason the exploitation of genetic resistance is the most sustainable method for reducing contamination. The review focuses on the significant advances that have been made in the development of transcriptomic, genetic and genomic information for maize, Fusarium verticillioides molds, and their interactions, over recent years. Findings from transcriptomic studies have been used to outline a specific model for the intracellular signaling cascade occurring in maize cells against F. verticillioides infection. Several recognition receptors, such as receptor-like kinases and R genes, are involved in pathogen perception, and trigger down-stream signaling networks mediated by mitogen-associated protein kinases. These signals could be orchestrated primarily by hormones, including salicylic acid, auxin, abscisic acid, ethylene, and jasmonic acid, in association with calcium signaling, targeting multiple transcription factors that in turn promote the down-stream activation of defensive response genes, such as those related to detoxification processes, phenylpropanoid, and oxylipin metabolic pathways. At the genetic and genomic levels, several quantitative trait loci (QTL) and single-nucleotide polymorphism markers for resistance to Fusarium ear rot deriving from QTL mapping and genome-wide association studies are described, indicating the complexity of this polygenic trait. All these findings will contribute to identifying candidate genes for resistance and to applying genomic technologies for selecting resistant maize genotypes and speeding up a strategy of breeding to contrast disease, through plants resistant to mycotoxin-producing pathogens

Genotyping by sequencing and QTL mapping for Fusarium ear rot resistance and fumonisin B1 accumulation in maize.

Fusarium verticillioides is the causal agent of Fusarium ear rot (FER) in maize and contaminates the grains with fumonisins, a family of mycotoxins that affects feed and food. Quantitative genetic variations exists for resistance to FER and fumonisin B1 accumulation among maize genotypes. Both traits have moderate to high heritability and Marker Assisted Selection of resistant genotypes is an attractive approach to control this problem in maize crops. In order to genetically dissect FER responses in maize and identify molecular markers associated with resistance loci, a cross from the resistant CO441 and the susceptible CO354 parents was generated and F2:3 segregant maize families were evaluated for resistance to FER and fumonisin B1 accumulation in both 2011 and 2012. Phenotyping was conducted on artificially inoculated F3 ears at 15 days after pollination (DAP) with two side-needle inoculation methods. FER resistance was evaluated at maturity as a percentage of infected kernels on the ears. Fumonisin B1 accumulation in the grains was predicted by NIR spectroscopy. In parallel, a molecular linkage map was constructed for the CO441xCO354 progeny using a Genotyping-by-Sequencing (GBS) approach. GBS provides low cost, high-density information useful to develop highly saturated linkage maps and to add new value to traditional bi-parental mapping and breeding populations. In total 157 F3 DNA pools and the parents were restricted with ApeKI, 96-plex barcoded libraries were constructed according to the Elshire protocol (PLoS ONE 6(5):e19379) and sequenced on an Illumina HiSeq2000 instrument. Initial analyses identified a set of 16.236 SNP markers. Stringent criteria were applied for SNP calling and filtering included a minimum quality score of 20 (Phredscale) for reads bases and a minimum reads mapping quality of 30 (Phred-scale), absence of missing data in the reference samples, less than 30% missing data in the population for each SNP filters on segregation distortion and linkage disequilibrium. Finally a set of 339 SNPs were integrated with genotyping data for 72 SSRs to construct a linkage map. A total of 31 QTLs (four traits in two different years) were detected, using IM and MQM analysis, in five main chromosomal regions

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis

OBJECTIVE:First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.DATA SOURCES:A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded.METHODS OF STUDY SELECTION:Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs.TABULATION, INTEGRATION, AND RESULTS:We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward.CONCLUSION:Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis

OBJECTIVE:First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.DATA SOURCES:A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded.METHODS OF STUDY SELECTION:Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs.TABULATION, INTEGRATION, AND RESULTS:We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward.CONCLUSION:Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone