Sets Of Twins Research Articles

School-Age Outcomes of Early Intervention for Preterm Infants and Their Parents: A Randomized Trial.

To examine the child and parental outcomes at school age of a randomized controlled trial of a home-based early preventative care program for infants born very preterm and their caregivers. At term-equivalent age, 120 infants born at a gestational age of <30 weeks were randomly allocated to intervention (n = 61) or standard care (n = 59) groups. The intervention included 9 home visits over the first year of life focusing on infant development, parental mental health, and the parent-infant relationship. At 8 years' corrected age, children's cognitive, behavioral, and motor functioning and parental mental health were assessed. Analysis was by intention to treat. One hundred children, including 13 sets of twins, attended follow-up (85% follow-up of survivors). Children in the intervention group were less likely to have mathematics difficulties (odds ratio, 0.42; 95% confidence interval [CI], 0.18 to 0.98; P = .045) than children in the standard care group, but there was no evidence of an effect on other developmental outcomes. Parents in the intervention group reported fewer symptoms of depression (mean difference, -2.7; 95% CI, -4.0 to -1.4; P < .001) and had reduced odds for mild to severe depression (odds ratio, 0.14; 95% CI, 0.03 to 0.68; P = .0152) than parents in the standard care group. An early preventive care program for very preterm infants and their parents had minimal long-term effects on child neurodevelopmental outcomes at the 8-year follow-up, whereas primary caregivers in the intervention group reported less depression.

High-specificity bioinformatics framework for epigenomic profiling of discordant twins reveals specific and shared markers for ACPA and ACPA-positive rheumatoid arthritis.

BackgroundTwin studies are powerful models to elucidate epigenetic modifications resulting from gene–environment interactions. Yet, commonly a limited number of clinical twin samples are available, leading to an underpowered situation afflicted with false positives and hampered by low sensitivity. We investigated genome-wide DNA methylation data from two small sets of monozygotic twins representing different phases during the progression of rheumatoid arthritis (RA) to find novel genes for further research.MethodsWe implemented a robust statistical methodology aimed at investigating a small number of samples to identify differential methylation utilizing the comprehensive CHARM platform with whole blood cell DNA from two sets of twin pairs discordant either for ACPA (antibodies to citrullinated protein antigens)-positive RA versus ACPA-negative healthy or for ACPA-positive healthy (a pre-RA stage) versus ACPA-negative healthy. To deconvolute cell type-dependent differential methylation, we assayed the methylation patterns of sorted cells and used computational algorithms to resolve the relative contributions of different cell types and used them as covariates.ResultsTo identify methylation biomarkers, five healthy twin pairs discordant for ACPAs were profiled, revealing a single differentially methylated region (DMR). Seven twin pairs discordant for ACPA-positive RA revealed six significant DMRs. After deconvolution of cell type proportions, profiling of the healthy ACPA discordant twin-set revealed 17 genome-wide significant DMRs. When methylation profiles of ACPA-positive RA twin pairs were adjusted for cell type, the analysis disclosed one significant DMR, associated with the EXOSC1 gene. Additionally, the results from our methodology suggest a temporal connection of the protocadherine beta-14 gene to ACPA-positivity with clinical RA.ConclusionsOur biostatistical methodology, optimized for a low-sample twin design, revealed non-genetically linked genes associated with two distinct phases of RA. Functional evidence is still lacking but the results reinforce further study of epigenetic modifications influencing the progression of RA. Our study design and methodology may prove generally useful in twin studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0374-0) contains supplementary material, which is available to authorized users.

Excessive trabeculations in noncompaction do not have the embryonic identity

BackgroundVentricular noncompaction is characterized by excessive trabeculations and is associated with heart failure. The lesion is hypothesized to result from failed compaction and thus retention of embryonic trabeculations. Here, we assess for the first time the identity of trabeculations in noncompaction to test whether noncompacted hearts show retention of embryonic trabeculations. MethodsUsing immunohistochemistry, we analyzed cardiac sections of the heart of a control embryo, 3 cases of fetal noncompaction (a set of twins and an unrelated fetus) and 3 fetal hearts without noncompaction. ResultsIn the embryo, the ventricular trabeculations strongly expressed ANF/NPPA whereas the compact wall did not. In the noncompaction hearts, trabeculations constituted an excessively thick layer. In noncompaction and control fetal hearts alike, however, only a miniscule subset of sub-endocardial myocardium of the trabeculations most proximal to the central ventricular lumen exhibited strong expression of ANF/NPPA, representing Purkinje myocardium. The trabeculations of both fetal control and noncompaction hearts were ANF-negative and orders of magnitude wider than those of the embryo. Both the compact and noncompaction trabeculated myocardium were rich in coronary vasculature. Like embryonic trabeculations, the ANF+ Purkinje myocardium had little if any vasculature. ConclusionThe excessive trabeculations in noncompaction do not have the embryonic identity and noncompaction is probably not the result of failed compaction. We propose the lesion results from the compact wall growing into the ventricular lumen in a trabecular fashion.

Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study

Data from previous studies have suggested a possible association between antibiotic use in infancy and risk of childhood obesity, with implications for health-care delivery and obesity prevention strategies. However, whether the observed association was due to antibiotic use or underlying infection, or both, is unclear. We aimed to disentangle the effect of antibiotic use in infancy from that of underlying infection on the risk of childhood obesity. In this longitudinal birth cohort study, we included infants in the Kaiser Permanente Northern California population born between Jan 1, 1997, and March 31, 2013. We used electronic medical records to ascertain data for antibiotic use, infection diagnosis, and anthropometric measurements (and thus BMI and obesity status) from birth up to age 18 years. We used standard mixed-effects logistic regression for repeated measurements to analyse multiple BMI measurements per child (median five measurements) and to obtain odds ratios (ORs) and 95% CIs for obesity risk. We also did a substudy in 547 same-sex twin pairs with discordant exposure status to substantiate our findings. 260 556 individuals were included in our analysis. After controlling for maternal age, race or ethnic origin, pre-pregnancy BMI, preterm delivery, low birthweight, maternal antibiotic use, and infection during pregnancy, infection without antibiotic use in infancy was associated with an increased risk of childhood obesity compared with controls without infection (OR 1·25, 95% CI 1·20-1·29). A clear dose-response relation was seen between infection episodes and risk of childhood obesity (ptrend <0·0001). By contrast, compared with infants with untreated infection, antibiotic use during infancy was not associated with risk of childhood obesity (1·01, 0·98-1·04). Neither broad-spectrum nor narrow-spectrum antibiotics were associated with risk of childhood obesity. These findings were supported by the results of the twin set analysis. Infection, but not antibiotic use, during infancy is associated with risk of childhood obesity. This finding will need to be replicated in future studies. Although our results do not rule out a potential effect of antibiotics on microbiome composition and the use of antibiotics should always be judicious, they suggest that treatment of common infections with antibiotics in infancy is unlikely to be a main contributor to childhood obesity. Kaiser Permanente Center for Effectiveness & Safety Research.

Complex systems in human development: sexual dimorphism in teeth and fingerprints of Australian twins

Human teeth and fingerprints have similar embryological origin from epithelial-mesenchymal interactions. This study aims to determine the nature and extent of sexual dimorphism in fingerprints and teeth of twins; investigate the influences of genetic, epigenetic and environmental factors on observed variation; identify possible developmental associations between the phenotypes; and explore whether both systems display the features of complex adaptive systems. Mesiodistal (MD) measurements from both primary and permanent teeth and ridge density (RD) from three different finger areas, namely ulnar (U), radial (R), and proximal (P), from fingerprints of the same set of monozygotic and dizygotic Australian twins (28 males and 31 females aged 8 to 10 years, and aged 13 to 16 years, respectively) were collected and analysed. Sexual dimorphism was observed in both the primary and permanent dentitions, with the latter showing greater magnitude of differences than the former. There was no observed sexual dimorphism in the fingerprints of the 8 to 10 year cohort, but a few finger areas (left index U, right index R, left little R, and left little P) of the 13- to 16-year cohort exhibited significant differences, showing that friction ridges expand over time. It was concluded that both dentition and dermatoglyphics display characteristics of complex adaptive systems.

Higher pregnancy rates with zona-free euploid blastocysts

A small percentage of embryos undergoing assisted hatching on Day 3 for Day 5/6 biopsy will hatch completely prior to vitrification, thus resulting in zona pellucida (ZP)-free embryos. Prior studies comparing ZP free to ZP intact blastocyst transfers have found either no difference or only moderate improvement in pregnancy rates with the transfer of ZP-free embryos. No studies have explored the relationship between the loss of the ZP as a result of embryo biopsy and subsequent pregnancy outcomes. The objective of this study was to compare embryo survival, implantation rates and pregnancy rates of thawed, euploid-PGS embryos frozen with and without a zona. A retrospective cohort study Patients who underwent a single embryo transfer (SET) of a euploid embryo previously biopsied and vitrified with or without a ZP between Jan 2013 through Feb 2016 were included in the study. Embryos were laser hatched on day 3, biopsied and vitrified on day 5 or 6. Group 1 consisted of 11 patients (mean age=37, range 31-41) whose embryos were fully hatched with no ZP. Group 2 consisted of 193 patients (mean age=37, range 25-45) with an intact ZP. Post-warming survival, implantation and clinical pregnancy (heartbeat) rates were calculated. Two-sided Fisher Exact test was used. Statistical significance was defined at p<.05. Post warming survival rate was 100% for both groups. Implantation and pregnancy rates (IR and PR) for Group 1 were 81.8% (9/11). All pregnancies were singleton. IR and PR for Group 2 were 49.2% (95/193) and 47.7% (92/193) respectively. Group 2 had three sets of monozygotic twins (MZT). While both IR and PR were better in the ZP-free group, only PR reached statistical difference.Tabled 1Implantation Rate and Pregnancy Rate in Zona Free Group vs. Zona Intact GroupZona Free-Group 1 (n=11)Zona-Intact Group 2 (n=193)p-valueImplantation Rate81.8% (9/11)49.2% (95/193) 3xMZT.06Pregnancy Rate81.8% (9/11)47.7% (92/193).03 Open table in a new tab 1. ZP-free euploid blastocysts resulted in a significantly higher pregnancy rate compared to ZP-intact blastocysts.

Twin tropical cyclones in the Indian Ocean: the role of equatorial waves

This study explores the background atmospheric conditions that led to the development of recent two sets of twin tropical cyclones in the Indian Ocean. One set of twins formed in late December 2011 (“pair A”) and other in May 2013 (“pair B”). An extensive area of active convection prevailing over wide-equatorial region and low-level westerly wind over near-equatorial region is major precursors to the two cases of twins. Convection and accompanying westerlies slowly strengthen, and the two sets of twins tend to emerge within it. The atmospheric equatorial convectively coupled Kelvin wave (CCKW) and convectively coupled equatorial Rossby (CCER) wave played key role in the formation of the two twins’ events. Wave-enhanced equatorial convection and low-level westerly anomalies produced by the combination of CCKW and CCER wave are crucial for the development of “pair A” twins. CCKW prior to “pair B” twins produced convection and westerly anomalies over equatorial region. The equatorial westerlies are further modulated by CCER wave favoring twins of “pair B.” Moreover, convection reinforced by CCER wave in OLR aided occurrence of Northern Hemispheric cyclone of “pair A” and Southern Hemispheric cyclone of “pair B.” While the CCKW and CCER wave appear to be associated with the formation of the two twin cyclone cases, more thorough understanding of the mechanisms involved needs considerable attention in forthcoming research.

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study.

BackgroundPatients with multiple sclerosis (MS) or Crohn’s disease (CD) being treated with natalizumab (Tysabri®, Biogen) who are planning to become pregnant or discover they are pregnant after exposure to natalizumab are currently advised to balance the potential benefits and potential risks of exposure when considering treatment options. This study was undertaken to evaluate pregnancy outcomes of women with MS or CD who were exposed to natalizumab at any time within 3 months prior to conception or during pregnancy. A pregnancy registry was created to better understand the effect of natalizumab exposure on pregnancy outcomes.MethodsThe Tysabri Pregnancy Exposure Registry was a global, observational exposure registration and follow-up study. Evaluations included spontaneous abortions (<22 weeks gestational age), fetal losses (≥22 weeks gestational age), ectopic pregnancies, elective or therapeutic terminations, stillbirths, birth defects, and live births. Birth defects were reviewed and coded in accordance with the Metropolitan Atlanta Congenital Defects Program (MACDP) classification of birth defects.ResultsA total of 369 patients with MS and 7 patients with CD were enrolled prospectively, of whom 355 patients (99.4 %; 349 MS and 6 CD) had known pregnancy outcomes (including 8 twin sets). The spontaneous abortion rate was 9.0 % (n = 32; 95 % confidence interval [C. I.], 6.3–12.5 %). An independent advisory committee review determined the major birth defect rate to be 5.05 % (16 of 316 live births + 1 elective abortion; 95 % C. I., 2.9–8.1 %). The mean gestational age of the live-born infants was 38.3 weeks, and the mean birth weight was 3158.3 g.ConclusionsAlthough the overall rate of birth defects was higher than that observed by the MACDP, these registry outcomes showed no specific pattern of malformations that would suggest a drug effect, and the spontaneous abortion rate was consistent with that of the general population.Trial registrationClinicalTrials.gov NCT00472992 (11 May 2007).

The relationship between the shape of the first metatarsal head and hallux valgus deformity

Foot impressions are of utmost importance in crime scene investigations. Foot impressions are available in the form of barefoot prints, sock-clad footprints, and as impressions within footwear. Sometimes suspects leave their footwear at the crime scene, and the insole of this footwear may contain the foot impression of the suspect which may be important evidence linking him or her to the crime. The task of identification based on the analysis of footprints can be challenging when the footprints belonging to one of the identical twin is available for examination. The present study is based on the quantitative measures of the foot impressions in the footwear of adult identical twins. The study was conducted on four sets of female monozygotic twins from the United States of America. A total of 17 length and breadth measurements were taken on each foot impression. A combination of Reel Method and Extended Gunn Method was utilized to produce the measurements. The measurements of the foot impressions were compared among the twins on the right and the left side. Differences were found in the various footprint measurements among the twins. The study's sample size was not large enough to apply robust statistical tests, but the study is significant in that it presents the first detailed comparative analysis of a large number of measurements of insole foot impressions of adult twins. The observations derived from the study are likely to assist forensic investigations in cases involving the foot impressions of the twins.

Neurodevelopmental Disorders or Early Death in Siblings of Children With Cerebral Palsy.

To explore the presence of shared underlying causes of cerebral palsy (CP) and other neurodevelopmental disorders, by examining risks of other disorders in siblings of children with CP. We used Norwegian national registries to identify 1.4 million pairs of full siblings (singletons) and 28 000 sets of twins born from 1967 to 2006, identify stillbirths and neonatal deaths, and find individuals with CP, epilepsy, intellectual disability, autism spectrum disorders, attention-deficit/hyperactivity disorder, blindness, deafness, schizophrenia, and bipolar disorder. Associations between CP in 1 sibling and neurodevelopmental disorders or early death in other siblings were estimated using logistic regression models. There were 5707 neonatal survivors (beyond 28 days) with CP (2.5/1000). These children had substantial comorbidity (eg, 29% had epilepsy). Singleton siblings of (singleton) children with CP had increased risks of neurodevelopmental problems, including epilepsy (odds ratio [OR], 1.8 [95% confidence interval (CI), 1.5-2.5]), intellectual disability (OR, 2.3 [95% CI, 1.8-2.9]), autism spectrum disorders (OR, 1.6 [95% CI, 1.1-2.2]), attention-deficit/hyperactivity disorder (OR 1.3 [95% CI, 1.1-1.6]), blindness (OR 2.4 [95% CI, 1.1-5.4]), and schizophrenia (OR 2.0 [95% CI, 1.2-3.2]). There was no increase in risk of bipolar disorder (OR 1.0 [95% CI, 0.6-1.6]). Families with children with CP also had increased risk of losing another child in the perinatal period (stillbirth OR, 1.8 [95% CI, 1.5- 2.3]; neonatal death OR, 1.7 [95% CI, 1.3-2.2]). Associations were stronger within sets of twins. Siblings of a child with CP were at increased risk for a variety of other neurodevelopmental morbidities, as well as early death, indicating the presence of shared underlying causes.

Risk factors associated with Cryptosporidia, Eimeria, and diarrhea in smallholder dairy farms in Mukurwe-ini Sub-County, Nyeri County, Kenya.

Aim:This study was undertaken to determine the household, calf management, and calf factors associated with the occurrence of Eimeria, Cryptosporidia, and diarrhea in pre-weaned calves reared in smallholder dairy farms in Mukurwe-ini Sub-County of Nyeri County, Kenya. In addition, the study also evaluated factors associated with average daily weight gain in the same pre-weaned calves.Materials and Methods:A total of 112 newborn calves (63 males and 49 females) on 111 farms (1 set of twins) were followed for 2 months between June 2013 and August 2013. Two calves were lost to follow-up. A pre-tested questionnaire was used to collect data on household characteristics and calf management practices in the 111 selected farms. On the first visit to the farm (within 7 days of the birth of the calf), blood samples were collected from the jugular vein to assess the level of maternal immunity acquired by the calf, by determining the serum total protein and selenium concentration. At 4 and 6 weeks of age, fecal samples from the calves were collected to assess the presence of Cryptosporidia and Eimeria oocysts. Every 2 weeks for 2 months, the calves and their environments were examined, their 2-week consumption and health history were recorded, and weights were estimated with a weight tape. Each of the factors was evaluated in a univariable regression model and only those found to be significant (p≤0.20) were included in a multivariable model. Elimination of non-significant factors was done in the multivariable model through a backward elimination procedure so that only those variables which were confounders, and/or significant at (p≤0.05) remained in the final model.Results:About 37% (41/110) of the calves experienced diarrhea at least once during the 2-month study period. The overall period prevalence of Eimeria and Cryptosporidia was 42.7% (47/110) and 13.6% (15/110), respectively. Low serum protein was associated with 1.8 and 2.4 times the odds of Eimeria and Cryptosporidia infections, respectively. Lack of supervision of calf birth and low serum total protein were both associated with 1.3 times the odds of diarrhea incidence. Dirty calf pens, feeding <5 L of milk/day, and infection with Eimeria were associated with 0.105, 0.087, and 0.059 kg, respectively, reduced average daily weight gain of the calves.Conclusion:In the Kenyan context, calf diarrhea risk could be reduced through better supervision of parturition and colostrum provision. Specifically, the risk of Eimeria and Cryptosporidia infections could be reduced by optimizing the passive transfer of immunity to the newborn calves. Average weight gains of calves could be improved by good colostrum provision, pen hygiene, and preventing Eimeria infections.

Treadmill exercise within lower-body negative pressure attenuates simulated spaceflight-induced reductions of balance abilities in men but not women.

Spaceflight causes sensorimotor adaptations that result in balance deficiencies on return to a gravitational environment. Treadmill exercise within lower-body negative pressure (LBNP) helps protect physiological function during microgravity as simulated by bed rest. Therefore, we hypothesized that treadmill exercise within LBNP would prevent balance losses in both male and female identical twins during 30 days of 6° head-down tilt bed rest. Fifteen (seven female and eight male) identical twin sets participated in this simulation of microgravity. Within each twin pair, one twin was randomly assigned to an exercise group that performed 40 min of supine treadmill exercise within LBNP set to generate 1.0–1.2 body weight, followed by 5 min of static feet-supported LBNP, 6 days per week. Their identical sibling was assigned to a non-exercise control group with all other bed rest conditions equivalent. Before and immediately after bed rest, subjects completed standing and walking rail balance tests with eyes open and eyes closed. In control subjects, standing rail balance times (men: −42%, women: −40%), rail walk distances (men: −44%, women: −32%) and rail walk times (men: −34%, women: −31%) significantly decreased after bed rest. Compared with controls, treadmill exercise within LBNP significantly attenuated losses of standing rail balance time by 63% in men, but the 41% attenuation in women was not significant. Treadmill exercise within LBNP did not affect rail walk abilities in men or women. Treadmill exercise within LBNP during simulated spaceflight attenuates loss of balance control in men but not in women.

Linkage to Care, Early Infant Diagnosis, and Perinatal Transmission Among Infants Born to HIV-Infected Nigerian Mothers: Evidence From the Healthy Beginning Initiative.

Background:In 2014, Nigeria accounted for 33% of all new childhood HIV infections that occurred among the 22 Global Plan priority countries where 80% of HIV-infected women reside. Even with a vertical HIV transmission rate of 27%, only 6% of infants born to HIV-infected women in Nigeria receive early infant diagnosis (EID). This article reports rates of antiretroviral prophylaxis, EID, and mother-to-child transmission in a congregation-based Healthy Beginning Initiative (HBI) designed to increase HIV testing among pregnant women in southeast Nigeria.Methods:This is a nested cohort study of HIV-exposed infants (HEI) within the HBI trial originally designed as a 2-arm cluster randomized trial. HIV-infected mothers and infants were followed between January 2013 and August 2014.Results:Across both arms of the study, 72 HIV-infected women delivered 69 live infants (1 set of twins) and 4 had miscarriages. Of the 69 live-born HEI, HIV status was known for 71% (49/69), 16% (11/69) died before sample collection, and 13% (9/69) were lost to follow-up. Complete information was available for 84% of HEI (58/69), of which 64% (37/58) received antiretroviral prophylaxis. Among the 49 infants tested for HIV, 88% (43/49) received EID within 2 months and 12% (6/49) received antibody testing after 18 months. The mother-to-child transmission rate was 8.2% (4/49).Conclusions:EID was higher and HIV transmission rate was lower among the HBI participants compared to reported rates in 2014. However, further progress is needed to achieve goals of elimination of infant HIV infection.

Ventilation of Preterm Infants during Delayed Cord Clamping (VentFirst): A Pilot Study of Feasibility and Safety.

Background Establishing lung inflation prior to umbilical cord clamping may improve the cardiovascular transition and reduce the risk of intraventricular hemorrhage in preterm infants. We developed a pilot feasibility and safety study in which infants < 33 weeks' gestation received assisted ventilation during delayed cord clamping (DCC). Methods Infants born between 24 0/7 and 32 6/7 weeks' gestation whose mothers consented were enrolled. All infants received continuous positive airway pressure or positive pressure ventilation during 90 seconds of DCC. Outcomes included feasibility (ability to complete protocol and maintain a sterile field during cesarean deliveries) and safety variables (Apgar scores, umbilical cord pH and base deficit, admission temperature, and postcesarean infection). Results A total of 29 infants were enrolled, including one set of twins (median gestation: 30 weeks; 72% cesarean births). In all cases, the protocol was completed. Heart rate at 60 seconds was more than 100 beats per minute in all infants. Apgar scores, cord blood gas values, and admission temperature were comparable to other preterm deliveries at our institution. Conclusion Assisting ventilation of very preterm infants during 90 seconds of DCC is challenging but feasible and appears to be safe in this small pilot study. A randomized clinical trial is warranted to determine clinical benefit.

Syndrome disintegration: Exome sequencing reveals that Fitzsimmons syndrome is a co-occurrence of multiple events.

In 1987 Fitzsimmons and Guilbert described identical male twins with progressive spastic paraplegia, brachydactyly with cone shaped epiphyses, short stature, dysarthria, and "low-normal" intelligence. In subsequent years, four other patients, including one set of female identical twins, a single female child, and a single male individual were described with the same features, and the eponym Fitzsimmons syndrome was adopted (OMIM #270710). We performed exome analysis of the patient described in 2009, and one of the original twins from 1987, the only patients available from the literature. No single genetic etiology exists that explains Fitzsimmons syndrome; however, multiple different genetic causes were identified. Specifically, the twins described by Fitzsimmons had heterozygous mutations in the SACS gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), as well as a heterozygous mutation in the TRPS1, the gene responsible in Trichorhinophalangeal syndrome type 1 (TRPS1 type 1) which includes brachydactyly as a feature. A TBL1XR1 mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features with no genetic cause identified for his spasticity or brachydactyly. The findings show that these individuals have multiple different etiologies giving rise to a similar phenotype, and that "Fitzsimmons syndrome" is in fact not one single syndrome. Over time, we anticipate that continued careful phenotyping with concomitant genome-wide analysis will continue to identify the causes of many rare syndromes, but it will also highlight that previously delineated clinical entities are, in fact, not syndromes at all. © 2016 Wiley Periodicals, Inc.

Twin-Twin Transfusion Syndrome Confers Persistent Morbidity and Mortality

INTRODUCTION: Selective fetoscopic laser photocoagulation (SFLP) for pregnancies complicated by twin-twin transfusion syndrome (TTTS) has improved outcomes for this morbid condition. Our objective was to describe the obstetric and neonatal outcomes of pregnancies complicated by TTTS in a community-based cohort. METHODS: We retrospectively studied all diamniotic monochorionic (DiMo) twin sets evaluated between 2011–2014 at the perinatal center of Mercy Hospital St. Louis, a suburban referral center that performs 8,000 deliveries annually. Individual chart review was performed using our electronic health record. RESULTS: 65 DiMo twin sets were identified. TTTS was diagnosed in 25 (38%) of DiMo pregnancies, of which 23 (92%) were Caucasian and 19 (76%) privately insured. TTTS severity by Quintero stage in N (%): 4 (16) stage 1, 4 (16) stage 2, 10 (42) stage 3, 2 (8) stage 4, 5 (21) stage 5. The gestational age at diagnosis was 19.5±4.6 weeks (mean±SD). One pregnancy was electively terminated. 9 (41%) pregnancies had demise of one or both fetuses and 2 (9%) had neonatal demise. Of pregnancies with a live birth, gestational age was 28±6 weeks (mean±SD) and 11 (44%) resulted in hospital discharge of two live infants. 13 (52%) patients underwent SLFP at outside centers, following which the following complications developed (n): demise of one twin (2), monoamnionicity (2), preterm labor (5), abruption (2), PPROM (7). CONCLUSION: Despite improving treatments for TTTS, obstetric outcomes for this condition in our high-resource community setting remain poor.

411. Predicting Tumor Response to Oncolytic Virotherapy Using Dual Isotope SPECT/CT Imaging with NIS Reporter Gene and Duramycin

Oncolytic virotherapy is a promising modality for cancer therapy and diverse viruses from various families have been genetically engineered to be tumor selective anticancer agents. To obtain an early readout on tumor susceptibility to the oncolytic virus, and potential toxicity from off target viral infection, we have engineered our oncolytic viruses to encode the thyroidal sodium iodide symporter gene (NIS) to enable noninvasive longitudinal imaging of the pharmacokinetics and sites of virus spread. The high resolution images obtained from the new generation of small animal SPECT/CT or PET/CT machines enable us to visualize increasing numbers of infectious foci daily within the subcutaneous tumors and to establish a mathematical model to develop strategies that will improve the outcome of virotherapy. In this study, we used the oncolytic Vesicular Stomatitis Virus (VSV) encoding NIS to evaluate the kinetics of intratumoral viral spread, and the subsequent aftermath of tumor cell death by apoptosis. Through I-125 SPECT/CT and NIS imaging, we showed rapid VSV spread within the susceptible MPC-11 murine plasmacytoma tumors, and the infectious foci grew larger and increased in numbers over 5 days. Since SPECT imaging enables concurrent dual isotope imaging, we also gave the same animal Tc-99m duramycin that detects apoptotic cells. In this MPC-11 model, we found rapid onset of apoptosis within the tumor. The infectious foci of viral infection (NIS imaging) and cell death (duramycin imaging) were coincident, overlapping at the acute phase of infection. In contrast, the CT-26 tumor was significantly less responsive to VSV-mIFN-NIS therapy, and there was minimal positive NIS signals or apoptosis. We are keen to further evaluate the potential of using dual isotope SPECT imaging using NIS reporter gene and the duramycin apoptosis tracer, with the goal of using this twin set of imaging methods to give us an early prediction of tumor response to oncolytic virotherapy.

Twin-to-twin transfusion syndrome and potential applicability to the Barker hypothesis

Twin-to-Twin Transfusion Syndrome (TTTS) carries significant risk of morbidity and mortality in affected monozygotic twin sets. As research into TTTS progresses, the effects of the adverse intrauterine environment on the long-term morbidities of TTTS survivors, is becoming more apparent. In TTTS, there is impaired vascular development and significant cardiac change in both foetuses, leading to high risk of long-term cardiac and neurologic morbidities in survivors. This appears to reflect the Barker Hypothesis of the Developmental Origins of Disease.This review will discuss the Barker Hypothesis and its potential applicability to TTTS. It will outline foetal development in TTTS and subsequent consequences for the neonate. Current TTTS research will be discussed in addition to relevant neonatal care provision.It will become evident that in order to improve long-term outcomes for TTTS survivors, a significant body of research focussing upon the correlation between foetal development in TTTS and associated adult disease states is required.

Lower Body Negative Pressure Treadmill Exercise Attenuates Simulated Space Flight‐Induced Reductions of Balance Abilities in Males but not Females

Spaceflight causes sensorimotor adaptations that result in balance deficiencies upon return to a gravitational environment. Lower Body Negative Pressure (LBNP) treadmill exercise has been shown to protect against deconditioning in various other physiological systems during simulated spaceflight. Therefore, we hypothesized that LBNP treadmill exercise prevents balance losses in both male and female identical twins during 30 days of 6° head‐down‐tilt (HDT) bed rest. Fifteen (8M and 7F) identical twin sets participated in 30 days of bed rest. Within each twin pair, one twin was randomly assigned to an exercise group that performed 40 min of supine LBNP treadmill exercise set to generate 1.0–1.2 body weight, followed by 5 min of static LBNP, 6 days/wk. Their identical sibling was assigned to a non‐exercise control group. Before and immediately after bed rest, subjects completed standing and walking rail balance tests with eyes open and eyes closed. In control subjects, standing rail balance times (men: −42%, women: −40%), rail walk distances (men: −44%, women: −32%), and rail walk times (men: −34%, women: −31%) significantly decreased after bed rest. Compared to controls, subjects in the LBNP treadmill exercise group showed significantly attenuated losses of standing rail balance time, with prevention of 63% of the loss in men, but without a significant prevention in women (41%). In addition, LBNP treadmill exercise mitigated decreases in rail walk time in men, but not in women. Therefore, treadmill exercise within LBNP during spaceflight may maintain balance control; yet this protective effect may, to some extent, depend on gender.Support or Funding InformationThis study was funded by NASA grants NAG 9‐1425, NCC2‐1133, NNX10AM18G, and NNX13AJ12G, NIH grant to the UCSD GCRC M01 RR00827. BRM was supported by National Space Biomedical Research Institute through NCC 9‐58. We thank our outstanding twins and staff at the UCSD General Clinical Research Center, as well as the UCSD Faculty Mentorship Program and the 2015 Julia Brown Research Scholarship.

Infantile Hemangiomas in Twins: A Prospective Cohort Study.

Twins have a higher-than-expected risk of infantile hemangiomas (IHs), but the exact reasons for this association are not clear. Comparing concordant and discordant twin pairs might help elucidate these factors and yield more information about IH risk factors. A prospective cohort study of twin pairs from 12 pediatric dermatology centers in the United States, Canada, Argentina, and Spain was conducted. Information regarding maternal pregnancy history, family history of vascular birthmarks, zygosity (if known), and pregnancy-related information was collected. Information regarding twins (N = 202 sets) included birthweight, gestational age (GA), presence or absence of IHs, numbers and subtypes of IHs, presence of other birthmarks, and other medical morbidities. Two hundred two sets of twins were enrolled. Concordance for IH was present in 37% of twin pairs. Concordance for IH was inversely related to gestational age (GA), present in 42% of GA of 32 weeks or less, 36% of GA of 33 to 36 weeks, and 32% of GA of 37 weeks or more. Twins of GA of 34 weeks or less were more than two and a half times as likely to be concordant as those of GA of 35 weeks or more (odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.42-4.99; p < 0.01). In discordant twins, lower birthweight conferred a high risk of IH; of the 64 sets of twins with 10% or greater difference in weight, the smaller twin had IH in 62.5% (n = 40) of cases, versus 37.5% (n = 24) of cases in which the higher-birthweight twin was affected. Zygosity was reported in 188 twin sets (93%). Of these, 78% were dizygotic and 22% monozygotic. There was no statistically significant difference in rates of concordance between monozygotic twins (43%, 18/42) and dizygotic twins (36%, 52/146) (p = 0.50). In multivariate analysis comparing monozygotic and dizygotic twins, adjusting for effects of birthweight and sex, the likelihood of concordance for monozygotic was not appreciably higher than that for dizygotic twins (OR = 1.14, 95% CI = 0.52-2.49). Female sex also influenced concordance, confirming the effects of female sex on IH risk. The female-to-male ratio was 1.7:1 in the entire cohort and 1.9:1 in those with IH. Of the 61 concordant twin sets with known sex of both twins, 41% were female/female, 43% were female/male, and 16% were male/male. These findings suggest that the origin of IHs is multifactorial and that predisposing factors such as birthweight, sex, and GA may interact with one another such that a threshold is reached for clinical expression.