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  • 1
    Language: English
    In: Pediatrics, March 2002, Vol.109(3), pp.473-8
    Description: There has been a major increase in the incidence of hypospadias in infants in the 1990s, but the risk factors are not known. Although there are scattered reports in the literature regarding the association of low birth weight and hypospadias, this has not been systematically studied. The objective of this study was to determine the association between early gestation intrauterine growth and hypospadias. A retrospective review of 13 years of admissions to 2 tertiary care neonatal intensive care units (NICUs) in Connecticut (1987--2000) showed that 112 (1.66%) of 6746 male infants had any degree of hypospadias. Of these, 8 were part of a genetic syndrome and were excluded. A retrospective cohort analysis of these 6738 infants was performed. Infant growth parameters at birth (weight, head circumference, and length) were analyzed along with maternal risk factors known to be associated with changes in fetal growth, including maternal age, race, diagnosis of preeclampsia, gestational diabetes, and maternal use of alcohol or tobacco or substance abuse during pregnancy. The incidence of hypospadias in the NICU population increased 10-fold from 0.4% in 1987 to 4% in the first quarter of 2000. Hypospadias was significantly more common in infants who had uniformly poor intrauterine growth (〈10th percentiles) in the various parameters measured: birth weight, length, or head circumference. There were no significant differences in maternal age or race, nor were there differences in the use of alcohol, tobacco, or street drugs by the mother. There were no differences between singletons and multiple-gestation births. However, the frequency of occurrence was significantly higher among first-born infants (1.9%) compared with all other infants (0.9%). The incidence of hypospadias in our NICU population has increased 10-fold during the 13-year period of study. There was a significant association of hypospadias with poor intrauterine growth. The growth restriction was probably of early gestational cause as there was proportionate involvement of somatic (weight and length) and brain growth (head circumference). The increasing frequency of hypospadias and its association with poor intrauterine growth originating in early gestation suggests that common environmental factor(s) that have an impact on both conditions may be involved.
    Keywords: Fetal Growth Retardation -- Complications ; Hypospadias -- Complications
    ISSN: 00314005
    E-ISSN: 1098-4275
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  • 2
    Language: English
    In: Journal of Alloys and Compounds, 05 May 2018, Vol.744, pp.801-808
    Description: Al-25 at.% Ni and Al-23.5 at.% Ni-1.5 at.% Cr alloys were synthesised via gas atomisation to study the effect of rapid cooling on the microstructure and phase composition of Raney type catalyst precursor powders. In the undoped powders, the three phases, Al₃Ni₂, Al₃Ni, and Al-Al₃Ni eutectic were identified, while in the Cr-doped powders the additional phase Al₁₃Cr₂ was also identified. Extensive substitution of Ni onto the Cr lattice sites is observed, which generates the observed phase fraction of Al₁₃Cr₂. Elemental mapping and quantitative image analysis of backscattered electron micrographs indicates that the Al₁₃Cr₂ phase precipitates late in solidification, probably direct from the melt, during the final stages of Al₃Ni growth. As such, this explains previous observations that Cr is found on the surface of the activated catalyst without the need to invoke migration of Cr. Leaching of such an Al-rich compound offers a plausible explanation for the enhanced catalytic activity observed in Cr-doped Raney catalysts.
    Keywords: Intermetallics ; Rapid-Solidification ; Microstructure ; Catalysis ; Metals and Alloys ; Engineering ; Chemistry ; Physics
    ISSN: 0925-8388
    E-ISSN: 1873-4669
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  • 3
    Language: English
    In: Antioxidants & redox signaling, 15 July 2012, Vol.17(2), pp.224-36
    Description: Epigenetic modifications are key processes in understanding normal human development and are largely responsible for the myriad cell and tissue types that originate from a single-celled fertilized ovum. The three most common processes involved in bringing about epigenetic changes are DNA methylation, histone modification, and miRNA effects. There are critical periods in the development of the zygote, the embryo, and the fetus where in the organism is most susceptible to epigenetic influences because of normal demethylation and de novo methylation processes that occur in the womb. A number of epigenetic modifications of normal growth patterns have been recognized, leading to altered development and disease states in the mammalian fetus and infant. 'Fetal programming' due to these epigenetic changes has been implicated in pathogenesis of adult-onset disease such as hypertension, diabetes, and cardiovascular disease. There may also be transgenerational effects of such epigenetic modifications. The impact of environmental agents and endogenous factors such as stress at critical periods of infant development has immediate, life-long and even multi-generational effects. Both the timing and the degree of insult may be important. Understanding these influences may help prevent onset of disease and promote normal growth. Use of one-carbon metabolism modifying agents such as folic acid during critical periods of epigenetic modulation may have significant clinical impact. Their use as therapeutic agents in targeted epigenetic modulation of genes may be the new frontier for clinical therapeutics.
    Keywords: Child Development ; Disease ; Epigenesis, Genetic
    ISSN: 15230864
    E-ISSN: 1557-7716
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  • 4
    Language: English
    In: American Journal of Obstetrics and Gynecology, January 2015, Vol.212(1), pp.S394-S394
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2014.10.1026 Byline: Kari Horowitz, Naveed Hussain, M. Sanders, Winston Campbell Author Affiliation: (1) University of Connecticut Health Center, Maternal Fetal Medicine, Farmington, CT (2) Connecticut Children's Medicial Center, Neonatology, Farmington, CT (3) University of Connecticut Health Center, Pathology, Farmington, CT
    Keywords: Medicine
    ISSN: 0002-9378
    E-ISSN: 1097-6868
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  • 5
    In: Obstetrics & Gynecology, 2017, Vol.129 Suppl 1, pp.117S-117S
    Description: INTRODUCTION:: Racial disparities exist in pregnancy outcomes and infant mortality. We explored whether in-hospital morbidity or mortality differed by race for preterm neonates admitted to a single academic institutionʼs NICU. METHODS:: Retrospective cohort analysis of preterm infants, under 37 weeks, within NIS-3 database from 1994-2009. Anomalies and aneuploidy were excluded. Primary outcome was death before discharge. Secondary outcomes were respiratory distress syndrome (RDS), interventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). Planned sub-analysis of very preterm (VPT) infants, under 28 weeks, was performed. Four racial groups were compared with odds ratio compared to Caucasian neonates (CN). Logistic regression was performed with P-value less than 0.05 significant. RESULTS:: 4,802 neonates were included. There was no difference across racial groups (RGs) in death before discharge (p=0.106). Mixed neonates had a 60% increased risk of in-hospital death (IHD) compared to CNs [OR 1.60 (1.05-2.40), p=0.026]. There was a significant reduction in RDS for all three RGs compared to CNs (p=0.004). There was no difference between RGs for IVH (p=0.280) or NEC (p=0.099). In the VPT cohort IHD, RDS and NEC did not differ across RGs (p=0.151, p=0.538, p=0.905, respectively). There was a significant increase in IVH across VPT RGs (p=0.038). Asian neonates accounted for majority of IVH morbidity compared to CNs [OR 3.21 (1.09-9.07), p=0.029]. CONCLUSION:: IHD does not differ across RGs in preterm neonates admitted to the NICU. CNs have a higher rate of RDS than other RGs.
    ISSN: 0029-7844
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  • 6
    In: Obstetrics & Gynecology, 2018, Vol.131 Suppl 1, pp.180S-180S
    Description: INTRODUCTION:: Opioid use in pregnancy doubled between 1998 and 2011. Neonatal abstinence syndrome (NAS) occurs in newborns exposed to opioids in-utero. Opioids delay gastric emptying and inhibit gastric motility in adults, however, it is unknown if opioids affect the fetal gastrointestinal system. We assessed whether gastric size in opioid-exposed fetuses predicts NAS treatment. METHODS:: We undertook a retrospective cohort study of maternal-neonatal dyads with chronic opioid use who delivered at our tertiary hospital January 2005 to April 2017. Primary outcome: treatment for NAS (3 consecutive Finnegan scores 〉8 or 3 scores 〉24 within 96 hours of life). Medical records were reviewed for maternal and neonatal demographics and fetal ultrasound images. Fetal gastric size was measured from abdominal circumference images using major and minor axis calculating an ellipse comparing this to the abdominal circumference to derive the gastric area ratio (GAR). Analysis was two-sided (alpha of 0.05) by t-test for continuous and chi square for categorical variables. RESULTS:: We identified 49 maternal-neonatal dyads. NAS treatment occurred in 67% (n=33) of neonates. Neonatal length of stay was longer [26.9 (days) ± 13.7 vs 8.2 ± 7.7, p〈0.001] and mean peak Finnegan scores were higher in infants treated for NAS (12 ± 3 vs 5 ± 3, p〈0.001). GAR was not different between groups [2.91 ± 1.5 (treatment) vs 2.85 ± 1.6 (no treatment), p=0.90] and did not predict NAS treatment. CONCLUSION:: Fetal GAR does not predict NAS treatment. More studies are needed to determine if an ultrasound marker predictive of NAS treatment exists.
    ISSN: 0029-7844
    Source: Copyright © 2013 Lippincott Williams & Wilkins. All rights reserved.〈img src=http://exlibris-pub.s3.amazonaws.com/LWW%20logo.png style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: NeoReviews, 09/2017, Vol.18(9), pp.e532-e543
    ISSN: 1526-9906
    E-ISSN: 1526-9906
    Source: CrossRef
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  • 8
    Language: English
    In: The Journal of Pediatrics, February 2011, Vol.158(2), pp.234-238.e1
    Description: To assess the genetic contribution to late-onset sepsis in twins in the newborn intensive care unit. A retrospective cohort analysis of twins born from 1994 to 2009 was performed on data collected from the newborn intensive care units at Yale University and the University of Connecticut. Sepsis concordance rates were compared between monozygotic and dizygotic twins. Mixed-effects logistic regression analysis was performed to determine the impact of selected nongenetic factors on late-onset sepsis. The influence of additive genetic and common and residual environmental effects were analyzed and quantified. One hundred seventy monozygotic and 665 dizygotic twin pairs were analyzed, and sepsis identified in 8.9%. Mean gestational age and birth weight of the cohort was 31.1 weeks and 1637 grams, respectively. Mixed-effects logistic regression determined birth weight (regression coefficient, −0.001; 95% CI, −0.003 to 0.000; = .028), respiratory distress syndrome (regression coefficient, 1.769; 95% CI, 0.943 to 2.596; 〈 .001), and duration of total parenteral nutrition (regression coefficient, 0.041; 95% CI, 0.017 to 0.064; 〈 .001) as significant nongenetic factors. Further analysis determined 49.0% ( = .002) of the variance in liability to late-onset sepsis was due to genetic factors alone, and 51.0% ( = .001) the result of residual environmental factors. Our data support significant genetic susceptibility to late-onset sepsis in the newborn intensive care unit population.
    Keywords: Medicine
    ISSN: 0022-3476
    E-ISSN: 1097-6833
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  • 9
    In: The New England Journal of Medicine, 2012, Vol.367(23), pp.2226-2232
    Description: Conventional cytogenetic testing offers low-resolution detection of balanced karyotypic abnormalities but cannot provide the precise, gene-level knowledge required to predict outcomes. The use of high-resolution whole-genome deep sequencing is currently impractical for the purpose of routine clinical care. We show here that whole-genome “jumping libraries” can offer an immediately applicable, nucleotide-level complement to conventional genetic diagnostics within a time frame that allows for clinical action. We performed large-insert sequencing of DNA extracted from amniotic-fluid cells with a balanced de novo translocation. The amniotic-fluid sample was from a patient in the third trimester of pregnancy who underwent amniocentesis because of severe polyhydramnios after multiple fetal anomalies had been detected on ultrasonography. Using a 13-day sequence and analysis pipeline, we discovered direct disruption of CHD7, a causal locus in the CHARGE syndrome (coloboma of the eye, heart anomaly, atresia of the choanae, retardation, and genital and ear anomalies). Clinical findings at birth were consistent with the CHARGE syndrome, a diagnosis that could not have been reliably inferred from the cytogenetic breakpoint. This case study illustrates the potential power of customized whole-genome jumping libraries when used to augment prenatal karyotyping. Translocation of chromosomes can result in disruption of genes. In this case report, a sequencing approach was used to identify the cause and effect of a translocation within 13 days, a period consistent with use of the approach in prenatal diagnosis. Deep sequencing of the whole genome holds diagnostic promise but is currently thought to be impractical for routine prenatal care. In contrast, large-insert mate-pair, or jumping-library, sequencing provides a tractable approach for immediate clinical application and could complement conventional prenatal diagnostics. The risk of major structural birth defects among live births in the United States is approximately 3%1 and is associated with inherited or de novo genetic rearrangements and mutations as well as with maternal factors, such as advanced age, certain clinical conditions, and exposure to teratogenic factors. Approximately 1 in 2000 prenatal cases analyzed with conventional karyotyping has a . . .
    Keywords: United States–Us ; DNA Sequencing ; Pregnancy ; Genomes ; Mutation ; Congenital Diseases ; Charge Syndrome ; Deoxyribonucleic Acid–DNA ; Genetic Counseling ; Pregnancy ; Cesarean Section ; Genomes ; Amniocentesis ; Metabolism ; Diagnosis ; Ultrasonography ; Ultrasonic Imaging ; Fetuses ; Prenatal Care ; Deoxyribonucleic Acid–DNA ; Medical Diagnosis;
    ISSN: 0028-4793
    E-ISSN: 1533-4406
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  • 10
    Language: English
    In: Journal of Obstetric, Gynecologic & Neonatal Nursing, May 2018, Vol.47(3), pp.451-463
    Description: To examine the effect of feeding type on microbial patterns among preterm infants and to identify feeding factors that promote the colonization of beneficial bacteria. PubMed, Cochrane Database of Systematic Reviews, Scopus, and the Cummulative Index of Nursing and Allied Health Literature were thoroughly searched for articles published between January 2000 and January 2017, using the keywords and Primary studies written in English and focused on the association between enteral feeding and gut microbiome patterns of preterm infants were included in the review. We independently reviewed the selected articles and extracted information using predefined data extraction criteria including study design, study participants, type of feeding, type and frequency of biospecimen (e.g., feces, gastric aspirate) collection, microbiological analysis method, and major results. In 4 of the 18 studies included in the review, researchers described the effects of milk products (mothers’ own milk, donor human milk, and formula). In 5 studies, the effects of prebiotics were assessed, and in 9 studies, the effects of probiotics on the gut microbiome were described. Mothers’ own breast milk feeding influenced the compositional structure of preterm infants’ gut microbial community and increased diversity of gut microbiota compared with donor human milk and formula feeding. The results of the use of prebiotics and probiotics varied among studies; however, the majority of the researchers reported positive bifidogenic effects on the development of beneficial bacteria. Mothers’ own milk is considered the best form of nutrition for preterm infants and the gut microbial community. Variation in fatty acid composition across infant feeding types can affect microbial composition. The evidence for supplementation of prebiotics and probiotics to promote the gut microbial community structure is compelling; however, additional research is needed in this area.
    Keywords: Donor Human Milk ; Feeding ; Formula ; Long-Chain Polyunsaturated Fatty Acids ; Microbiome ; Mother’s Own Milk ; Prebiotics ; Probiotics ; Systematic Review ; Medicine ; Nursing
    ISSN: 0884-2175
    E-ISSN: 1552-6909
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