Case Report: Analysis of Preserved Umbilical Cord Clarified X-Linked Anhidrotic Ectodermal Dysplasia With Immunodeficiency in Deceased, Undiagnosed Uncles

Family history is one key in diagnosing inborn errors of immunity (IEI); however, disease status is difficult to determine in deceased relatives. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is one of the hyper IgM syndromes that is caused by a hypomorphic variant in the nuclear factor kappa beta essential modulator. We identified a novel IKBKG variant in a 7-month-old boy with pneumococcal rib osteomyelitis and later found that his mother has incontinentia pigmenti. Genetic analysis of preserved umbilical cords revealed the same variant in two of his deceased maternal uncles. Analysis of preserved umbilical cord tissue from deceased relatives can provide important information for diagnosing IEI in their descendants.

Homologous Use of Umbilical Cord Tissue for Knee Pain

Context: Injection with homologously-used umbilical cord tissue allograft has not been adequately studied in patients suffering from knee pain. Objectives: The goal of this study is to determine if knee pain subjects who received cryopreserved umbilical cord tissue (UCT) injected into knee joints experience less knee pain, better function, decreased physical limitations, and reduction of medications (e.g., opiates, NSAIDs, and acetaminophen) over a 6-month period. Methods: Prior to initiation of this study, Institutional Review Board (IRB) approval was obtained. Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritic Index (WOMAC), and medication usage data were recorded for thirty (30) consenting knee pain subjects receiving UCT at a single site in the United States. Subject profile information was also gathered and utilized to gain further insight into any effects of age, gender, and BMI on pain improvement over time. Results: Mean resting VAS scores improved from 1.95 to 0.83 over 6 months (p<0.001), while mean VAS scores with activity improved from 6.28 to 2.87 (p<0.001) for the same period. There was no strong evidence of correlation found between gender and VAS scores (resting or with activity). However, there were statistically significant correlations found for both BMI vs. Pre-injection VAS with activity scores (r=0.402, p=.028) and Age vs. Pre-injection VAS with activity scores (r=0.434, p=.017). Mean WOMAC daily activity function scores improved from 44.7 to 18.5 over the same 6 months (p<.001). Overall, of the patients who used medications at the beginning of the study (18), 77.8% of them reduced or eliminated medication use. Conclusion: Analysis demonstrates that injection with UCT decreases pain, improves physical function, and allows for less medication use for at least 6 months.

Histological diagnosis of the luetic placenta

Kaufmann (Derm. Ztschr. Bd. 56, H. 5.29), examining histologically the placenta of mothers with syphilis, as well as the umbilical cord, thinks that with the nonspecific morphological changes of syph. placenta examination of umbilical cord tissue for the presence of sp. pal. gains in importance. The detection of spirochetes in organ pieces is purely scientific, but not practical. A. gives a detailed picture of changes in the syphilitic placenta and umbilical cord.

The Treasury of Wharton's Jelly

Background Postnatal umbilical cord tissue contains valuable mesenchymal progenitor cells of various differentiation stages. While mesenchymal stem cells are plastic-adherent and tend to differentiate into myofibroblastic phenotypes, some round cells detach, float above the adherent cells, and build up cell aggregates, or form spheroids spontaneously. Very small luminescent cells are always involved as single cells or within collective forms and resemble the common well-known very small embryonic-like cells (VSELs). In this study, we investigated these VSELs-like cells in terms of their pluripotency phenotype and tri-lineage differentiation potential. Methods VSELs-like cells were isolated from cell-culture supernatants by a process that combines filtering, up concentration, and centrifugation. To determine their pluripotency character, we measured the expression of Nanog, Sox-2, Oct-4, SSEA-1, CXCR4, SSEA-4 on gene and protein level. In addition, the cultured cells derived from UC tissue were examined regarding their potential to differentiate into three germ layers. Result The VSELs-like cells express all of the pluripotency-associated markers we investigated and are able to differentiate into meso- endo- and ectodermal precursor cells. Conclusions Umbilical cord tissue hosts highly potent VSELs-like stem cells. Graphical Abstract

Dichotomy in the Impact of Elevated Maternal Glucose Levels on Neonatal Epigenome

CONTEXT Antenatal hyperglycemia is associated with increased risk of future adverse health outcomes in both mother and child. Variations in offspring’s epigenome can reflect the impact and response to in utero glycemic exposure, and may have different consequences for the child. OBJECTIVE We examined possible differences in associations of basal glucose status and glucose handling during pregnancy with both clinical covariates and offspring cord tissue DNA methylation. RESEARCH DESIGN AND METHODS This study included 830 mother-offspring dyads from the GUSTO cohort. The fetal epigenome of umbilical cord tissue was profiled using Illumina HumanMethylation450 arrays. Associations of maternal mid-pregnancy fasting (FPG) and 2h plasma glucose (2hPG) post-75g oral glucose challenge (OGTT) with both maternal clinical phenotypes and offspring epigenome at delivery were investigated separately. RESULTS Maternal age, pre-pregnancy BMI and blood pressure measures were associated with both FPG and 2hPG; while Chinese ethnicity (p=1.9×10 -4), maternal height (p=1.1×10 -4), pregnancy weight gain (p=2.2×10 -3), pre-pregnancy alcohol consumption (p=4.6×10 -4), and tobacco exposure (p=1.9×10 -3) showed significantly opposite associations between the two glucose measures. Most importantly, we observed a dichotomy in the effects of these glycemic indices on the offspring epigenome. Offspring born to mothers with elevated 2hPG showed global hypomethylation. CpGs most associated with the two glucose measures also reflected differences in gene ontologies and had different associations with offspring birthweight. CONCLUSIONS Our findings suggest that two traditionally used glycemic indices for diagnosing gestational diabetes may reflect distinctive pathophysiologies in pregnancy, and have differential impacts on the offspring’s DNA methylome.

Connected by the cord—comparison of drug positivity rates and concentrations in a large cohort of paired umbilical cord and meconium specimens

Substance abuse during pregnancy has significant short- and long-term health, social, and legal implications. Hence, prompt determination of a neonate’s drug exposure status can aid the healthcare team in making treatment choices. Umbilical cord tissue (UC) and meconium are two commonly used specimens to detect fetal drug exposure. However, the current evidence on the sensitivity of one specimen over the other is both limited and conflicting. By utilizing a large cohort (n=4036) of paired UC and meconium samples originating from 13 states, we retrospectively investigated the qualitative and quantitative drug positivity rates for 31 analytes from 5 drug classes (i.e. cannabis, opioids, stimulants, barbiturates, and benzodiazepines). Semi-quantitative drug detection in UC samples was conducted by LC-MS-based assays, whereas an immunoassay screen preceded quantitative LC-MS analysis for meconium specimens. Data were analyzed using R-programming, Microsoft Excel, and GraphPad Prism packages. The overall drug positivity rate for UC was 56.57% compared to 52.38% in meconium. Opioids were the top drug class detected in UC at 35.53% compared to 20.64% in meconium. The detection rates for individual opioid analytes were also higher in UC (0.97-15.49%) relative to meconium (0.0 to 9.09%). Notably, 6-acetylmorphine (heroin metabolite) was only detected in UC (0.97%). In contrast, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC) was more frequently detected in meconium at 34.99% compared to 19.89% in UC. In the stimulant drug class, the overall amphetamine positivity rate was 7.73% in UC while 8.57% in the meconium specimens. Conversely, the cocaine positivity rate in the UC was 3.84% and 2.23% in meconium samples. In the barbiturate drug class, the positivity rate for butalbital was twice as high in UC (1.91%) relative to meconium (0.99%). Phenobarbital positivity rate was comparable in both matrices (~0.15%). The positivity rates for 6 common benzodiazepine drugs ranged from 0.40-0.94% in UC compared to 0.01-0.35% in meconium. Interestingly, a multidrug combination analysis revealed that THC−opioids was the most common two-drug combination detected in both matrices at a rate of 7.22% in UC compared to 5.39% in meconium. Subsequent examination of analyte concentrations between the two matrices revealed higher concentrations in meconium. THC was 48.13 times more concentrated in meconium relative to UC. Amphetamines and cocaine were 6.45-15.01 times more concentrated in meconium relative to UC. For the opioids, the overall concentrations were 21.61-1845.01 times higher in meconium specimens relative to UC. For barbiturates, butalbital had comparable concentrations in the two matrices whereas phenobarbital was 33.10 times more concentrated in the meconium. Lastly, benzodiazepines were overall 6.21-38.75 times more concentrated in meconium than UC. In conclusion, this study shows that despite most drugs being more concentrated in meconium, drug positivity rates were higher with UC for all analytes except THC and amphetamines, suggesting higher detection potential of the UC specimen.

A High Concentration of Polycyclic Aromatic Hydrocarbons in Umbilical Cord Tissue is Associated with An Increased Risk For Fetal Neural Tube Defects

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment and have detrimental effects on human health. Embryos are particularly susceptible to environmental insults such as PAHs. We examined the association between prenatal exposure to PAHs and the risk for fetal neural tube defects (NTDs). A case-control study was conducted with 119 NTD cases and 119 controls. A total of 16 PAHs in umbilical cord tissue, determined with gas chromatography–mass spectrometry, were used as in utero exposure markers. Logistic regression and Bayesian kernel machine regression (BKMR) were performed to evaluate the individual and overall effects of PAH exposure on the risk for NTDs, respectively. Median concentrations of 10 PAHs were significantly higher in cases than in controls. In logistic regression, concentrations of four PAHs above the median of all participants were significantly associated with an increased NTD risk, even when potential covariates were adjusted for: phenanthrene, 2.35-fold (95% confidence interval [CI] 1.04–5.34); fluoranthene, 2.37-fold (95% CI 1.02–5.48); pyrene, 2.41-fold (95% CI 1.04–5.62); and benzo(b)fluoranthene, 2.95-fold (95% CI 1.27–6.86). In BKMR, the risk for NTDs increased when PAH concentrations were all above their 65th percentile compared to their median, while no statistical association between a single compound and NTD risk was observed when the remaining nine PAHs were taken into consideration simultaneously. Together these results show that prenatal PAH exposure is a risk factor for NTDs in offspring.