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Relaxing Restriction On Prescription Delivery. Org Account. Offering Telemedicine. Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients.
Multivariate predictive modeling using the Elastic Net EN algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.
Supplementary information: Supplementary data are available at Bioinformatics online. We expanded the study to births and utilized a "within-mother" approach to permit methodologic inquiry about residual confounding. NHB women had higher frequency 7.
Using within-mother analysis did not produce substantially different results. Based upon our recent insights into the determinants of preterm birth, which is the leading cause of death in children under five years of age worldwide, we describe potential analytic frameworks that provides both a common understanding and, ultimately the basis for effective, ameliorative action. Our research on preterm birth serves as an example that the framing of any human health condition is a result of complex interactions between the genome and the exposome.
New discoveries of the basic biology of pregnancy, such as the complex immunological and signaling processes that dictate the health and length of gestation, have revealed a complexity in the interactions current and ancestral between genetic and environmental forces. Understanding of these relationships may help reduce disparities in preterm birth and guide productive research endeavors and ultimately, effective clinical and public health interventions.
Kernicterus resulting from severe neonatal hyperbilirubinaemia is a leading cause of preventable deaths and disabilities in low-income and middle-income countries, partly because high-quality intensive phototherapy is unavailable. Previously, we showed that filtered-sunlight phototherapy FSPT was efficacious and safe for treatment of mild-to-moderate neonatal hyperbilirubinaemia.
We aimed to extend these studies to infants with moderate-to-severe hyperbilirubinaemia. We did a prospective, randomised controlled non-inferiority trial in Ogbomoso, Nigeria-a simulated rural setting. Near-term or term infants aged 14 days or younger who were of 35 weeks or more gestational age and with total serum bilirubin concentrations at or above the recommended age-dependent treatment levels for high-risk neonates were randomly assigned to either FSPT or intensive electric phototherapy IEPT.
Randomisation was computer-generated, and neither clinicians nor the parents or guardians of participants were masked to group allocation. FSPT was delivered in a transparent polycarbonate room lined with commercial tinting films that transmitted effective phototherapeutic light, blocked ultraviolet light, and reduced infrared radiation.
Safety was defined as no sustained hypothermia, hyperthermia, dehydration, or sunburn and was based on all treatment days. Treatment was safe for all neonates. FSPT is safe and no less efficacious than IEPT for treatment of moderate-to-severe neonatal hyperbilirubinaemia in near-term and term infants.
We estimated racial-ethnic prevalence ratios and used multivariable logistic regression for risk factor comparisons. The prevalence of delivery at periviable gestation was 3. Nonwhite race-ethnicity, lower education, uninsured status, being U. Immune cell profiles provide valuable diagnostic information for hematologic and immunologic diseases.
Although it is the most widely applied analytical approach, flow cytometry is limited to liquid blood. Moreover, either analysis must be performed with fresh samples or cell integrity needs to be guaranteed during storage and transport.
We developed epigenetic real-time quantitative polymerase chain reaction qPCR assays for analysis of human leukocyte subpopulations. Epigenetic qPCR achieves both relative and absolute quantifications. Applied to dried blood spots, epigenetic immune cell quantification was shown to identify newborns suffering from various primary immunodeficiencies. Using epigenetic qPCR not only provides a precise means for immune cell counting in fresh-frozen blood but also extends applicability to dried blood spots.
This method could expand the ability for screening immune defects and facilitates diagnostics of unobservantly collected samples, for example, in underdeveloped areas, where logistics are major barriers to screening. The risk of developing treatment-warranted Type 1 retinopathy of prematurity ROP might be reduced in preterm infants by modifying certain systemic factors. There are steps that can be taken both early and late in the course of retinal vascular maturation that may potentially reduce an infant's risk of developing Type 1 ROP.
In prethreshold stage ROP without plus disease, a combination of supplemental oxygen, correction of severe anemia, and light adaptation to reduce rod photoreceptor oxygen consumption helped us to reduce ROP severity, and encouraged a return to a more physiologic retinal vascular maturation pattern.
Thus, it may be possible to reduce the risk of developing Type 1 ROP by making adjustments in certain systemic parameters aimed at reducing retinal hypoxia, thereby gently lowering pathologically elevated levels of vascular endothelial growth factor VEGF within the eye. Bf can be readily adapted to clinical use by determining Bf population parameters at current BT thresholds.
These parameters can be established using a plasma bilirubin binding panel BBP consisting of BT, Bf, and two empiric constants, the maximum BT BTmax and the corresponding equilibrium association bilirubin constant K. We investigated risks of preeclampsia phenotypes from potential residential pesticide exposures, including individual chemicals and 69 physicochemical groupings that were applied in the San Joaquin Valley of California during the study period, The study population was derived from birth certificate data linked with Office of Statewide Health Planning and Development maternal and infant hospital discharge data.
The following numbers of women with preeclampsia phenotypes were identified: with superimposed pre-existing hypertension with preeclampsia preeclampsia with gestational weeks and with gestational weeks ; with severe preeclampsia with gestational weeks and with gestational weeks ; and with mild preeclampsia with gestational weeks and with gestational weeks The reference population for these groups was , women who did not have diabetes gestational or pre-existing , did not have any hypertensive disorder, and who delivered at 37 weeks or later.
The frequency of any exposure was lower or about the same in each preeclampsia case group further delineated by gestational age , and month time period, relative to the frequency in reference population controls. Nearly all odds ratios were below 1. This study showed a general lack of increased risks between a range of agriculture pesticide exposures near women's residences and various preeclampsia phenotypes.
The majority of these macrophages are believed to be alternatively activated macrophages M2. Macrophage subtypes were confirmed by surface markers and characterized by gene expression profiles. To mimic the normal placental microenvironment, M2 were exposed to hypoxia and sex hormones progesterone, estrogen.
However, progesterone and estrogen treatment had minimal effects on angiogenic factor expression in M2. Thus, conditions that alter the placental oxygen microenvironment or macrophage response in early pregnancy might cause aberrant angiogenesis and vascular remodeling, and lead to abnormal placental vascular development.
The progesterone receptor PGR plays a central role in maintaining pregnancy and is significantly associated with medical conditions such as preterm birth that affects PGR has been evolving rapidly since the common ancestor of human and chimpanzee, and we herein investigated evolutionary dynamics of PGR during recent human migration and population differentiation.
Our study revealed substantial population differentiation at the PGR locus driven by natural selection, where very recent positive selection in East Asians has substantially decreased its genetic diversity by nearly fixing evolutionarily novel alleles.
On the contrary, in European populations, the PGR locus has been promoted to a highly polymorphic state likely due to balancing selection. Integrating transcriptome data across multiple tissue types together with large-scale genome-wide association data for preterm birth, our study demonstrated the consequence of the selection event in East Asians on remodeling PGR expression specifically in the ovary and determined a significant association of early spontaneous preterm birth with the evolutionarily selected variants.
To reconstruct its evolutionary trajectory on the human lineage, we observed substantial differentiation between modern and archaic humans at the PGR locus, including fixation of a deleterious missense allele in the Neanderthal genome that was later introgressed in modern human populations.
Taken together, our study revealed substantial evolutionary innovation in PGR even during very recent human evolution, and its different forms among human populations likely result in differential susceptibility to progesterone-associated disease conditions including preterm birth.
Noninvasive blood tests that provide information about fetal development and gestational age could potentially improve prenatal care. Ultrasound, the current gold standard, is not always affordable in low-resource settings and does not predict spontaneous preterm birth, a leading cause of infant death.
In a pilot study of 31 healthy pregnant women, we found that measurement of nine cell-free RNA cfRNA transcripts in maternal blood predicted gestational age with comparable accuracy to ultrasound but at substantially lower cost. In a related study of 38 women 23 full-term and 15 preterm deliveries , all at elevated risk of delivering preterm, we identified seven cfRNA transcripts that accurately classified women who delivered preterm up to 2 months in advance of labor.
These tests hold promise for prenatal care in both the developed and developing worlds, although they require validation in larger, blinded clinical trials. The stress-response protein heme oxygenase-1 HO-1 has protective anti-inflammatory properties. Recently, we reported a protective role of HO-1 using our non-surgical cecal slurry CS model in wild-type WT mouse pups.
Here, we extend these findings to investigate the association of HO-1 deficiency with sepsis severity. Heme treatment 24h prior to sepsis induction significantly increased liver HO activity, reduced mortality to Furthermore, induction of HO-1 significantly reduced the mortality even in Het pups.
Thus, we conclude that HO-1 plays an important role in the protection against preterm sepsis. Phototherapy was introduced in the early 's, and is the primary treatment of severe neonatal jaundice or Crigler-Najjar syndrome. Nevertheless, the potential biological effects of the products generated from the photodegradation of bilirubin during phototherapy remain unknown.
This is very relevant in light of recent clinical observations demonstrating that the use of aggressive phototherapy can increase morbidity or even mortality, in extremely low birthweight ELBW infants. The aim of our study was to investigate the effects of bilirubin, lumirubin LR, its major photo-oxidative product , and BOX A and B its monopyrrolic oxidative products on the central nervous system CNS using in vitro and ex vivo experimental models.
The effects of bilirubin photoproducts on cell viability and expression of selected genes were tested in human fibroblasts, three human CNS cell lines neuroblastoma SH-SY5Y, microglial HMC3, and glioblastoma U cell lines , and organotypic rat hippocampal slices.
Neither bilirubin nor its photo-oxidative products affected cell viability in any of our models. These findings might underlie the adverse outcomes observed in ELBW infants undergoing aggressive phototherapy. Heme oxygenase-1 HO-1 is a major regulatory enzyme in the immune system. We observed maternal immune response dysregulation during late gestational inflammation LGI , which may be mediated by HO Here, we extend these studies to examine the immune response of offspring.
Pups' splenic immune cells were characterized using flow cytometry. We showed not only age- but also genotype-specific and long-lasting T-cell dysregulation in pups after maternal LGI.
Maternal exposure to LGI can result in dysregulation of splenic T cells in offspring, especially in those with HO-1 deficiency.
We speculate that these immune alterations are the basis of adverse outcomes in neonates from mothers exposed to low-grade subclinical infections. To examine linkages between mitochondrial genetics and preterm birth by assessing the risk for preterm birth associated with the inheritance of nuclear haplotypes that are ancestrally distinct from mitochondrial haplogroup. Genome-wide genotyping studies of cohorts of preterm and term individuals were evaluated.
We determined the mitochondrial haplogroup and nuclear ancestry for individuals and developed a scoring for the degree to which mitochondrial ancestry is divergent from nuclear ancestry. Infants with higher degrees of divergent mitochondrial ancestry were at increased risk for preterm birth 0. Preterm birth PTB , or the delivery prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality.
In this study, we performed the largest reported genome-wide association study analysis on 1, cases of PTB and 12, ancestry-matched controls from the focusing on genomic fetal signals. We have queried several existing replication cohorts and found no support of these associations. We conclude that the fetal genetic contribution to PTB is unlikely due to single common genetic variant, but could be explained by interactions of multiple common variants, or of rare variants affected by environmental influences, all not detectable using a GWAS alone.
To establish baseline trends in fecal calprotectin, a protein excreted into the stool when there is neutrophilic inflammation in the bowel, in infants at risk for necrotizing enterocolitis NEC. We performed a prospective observational cohort study in infants with a birth weight of View details for PubMedID Glucosephosphate dehydrogenase G6PD deficiency is a common enzyme deficiency affecting more than million individuals worldwide.
Extreme neonatal hyperbilirubinemia, with its severe sequelae of bilirubin neurotoxicity and the potential of death, is the most devastating manifestation of G6PD deficiency. In a recent review of Favism, Luzzatto and Arese state that the pathophysiology of jaundice in G6PD-deficient neonates is different from that of favism, as there is little evidence of hemolysis in these infants.
To explore the role of hemolysis in neonatal hyperbilirubinemia associated with G6PD deficiency. Previously published works including studies of endogenous production of carbon monoxide CO , an index of heme catabolism, in hyperbilirubinemic G6PD-deficient neonates were reviewed to determine the role of hemolysis in this condition. Three studies demonstrated that endogenous CO production is elevated in G6PD-deficient neonates with extreme hyperbilirubinemia.
Hemolysis is an important pathogenetic factor in G6PD deficiency-associated neonatal hyperbilirubinemia. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods. We then analyzed the dynamic changes of both the human transcriptome and the microbiome of plasma during pregnancy from 60 women.
We observed that the plasma microbiome remained relatively stable during pregnancy. The bacteria Ureaplasma shows an increased prevalence and increased abundance at postpartum, which is likely to be associated with postpartum infection.
We demonstrated that cfRNA-seq can be used to monitor viral infections. We detected a number of human pathogens in our patients, including an undiagnosed patient with a high load of human parvovirus B19 virus B19V , which is known to be a potential cause of complications in pregnancy. Plasma cfRNA-seq demonstrates the potential to simultaneously monitor immune response and microbial infections during pregnancy. Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body.
Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1, blood samples collected from patients enabled us to assemble 7, contiguous regions contigs larger than 1 kbp, of which 3, are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification.
When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated. The role of genetic factors in the modulation of serum bilirubin levels and the pathophysiology of neonatal hyperbilirubinemia is being increasingly recognized. Polymorphisms of the HO-1 gene promoter may modulate transcriptional activity, thereby augmenting or attenuating HO-1 expression with resultant modulation of the production of bilirubin.
Few studies have related these polymorphisms to neonatal bilirubin metabolism and have reported conflicting results. In this clinical review, we surveyed the role of HO-1 gene promoter polymorphisms in the control of bilirubin production and further considered their role, if any, in the pathophysiology of neonatal hyperbilirubinemia.
California singleton live births from to were included. Despite its high mortality and morbidity, the molecular etiology underlying PTB has been unclear.
Numerous studies have been devoted to identifying genetic factors in maternal and fetal genomes, but so far few genomic loci have been associated with PTB. By analyzing whole-genome sequencing data from trio families, for the first time, we observed the role of fetal de novo mutations in PTB. We observed a significant increase in de novo mutation burden in PTB fetal genomes. Our genomic analyses further revealed that affected genes by PTB de novo mutations were dosage sensitive, intolerant to genomic deletions, and their mouse orthologs were likely developmentally essential.
These genes were significantly involved in early fetal brain development, which was further supported by our analysis of copy number variants identified from an independent PTB cohort. Our study indicates a new mechanism in PTB occurrence independently contributed from fetal genomes, and thus opens a new avenue for future PTB research. Despite clear differences in immune system responses and in the prevalence of autoimmune diseases between males and females, there is little understanding of the processes involved.
Functional and phenotypic characterization of peripheral blood neutrophils revealed more mature and responsive neutrophils in young females, which also exhibited an elevated capacity in neutrophil extracellular trap formation at baseline and upon microbial or sterile autoimmune stimuli.
The expression levels of the immature-like neutrophil signature increased linearly with pregnancy, an immune state of increased susceptibility to certain infections. Using mass cytometry, we also find increased frequencies of immature forms of neutrophils in the blood of women during late pregnancy.
Thus, our findings show novel sex differences in innate immunity and identify a common neutrophil signature in males and in pregnant women. To evaluate the association between newborn acylcarnitine profiles and the subsequent development of necrotizing enterocolitis NEC with the use of routinely collected newborn screening data in infants born preterm. A retrospective cohort study was conducted with the use of discharge records for infants born preterm admitted to neonatal intensive care units in California from to who had linked state newborn screening results.
A model-development cohort of 94 preterm births from to was used to develop a risk-stratification model that was then applied to a validation cohort of 22 births from Fourteen acylcarnitine levels and acylcarnitine ratios were associated with increased risk of developing NEC.
Six acylcarnitine levels, along with birth weight and total parenteral nutrition, identified Abnormal fatty acid metabolism was associated with prematurity and the development of NEC. Metabolic profiling through newborn screening may serve as an objective biologic surrogate of risk for the development of disease and thus facilitate disease-prevention strategies.
Preterm sepsis is characterized by systemic bacterial invasion and inflammatory response. Its pathogenesis is unclear due to lack of proper animal models. Heme oxygenase-1 HO-1 can affect physiologic and pathologic conditions through its anti-inflammatory, antioxidative, and anti-apoptotic properties.
Since HO-1 is developmentally regulated, it may play a role in the pathogenesis of preterm sepsis. For this study, sepsis was induced using the non-surgical "cecal slurry" CS model. CS was given intraperitoneally at various doses to 4-day-old newborn mice to determine dose-dependent effects. The LD40 was then given and changes in bodyweight, bacterial colonization of organs, hematology, serum biochemistry, and immunomodulatory gene expression were determined.
We found a dose-dependent mortality with an LD40 of 2. Significant bacterial colonization and hematological changes leukocytopenia, thrombocytopenia, and lymphocytopenia and increased gene expression of pro-inflammatory cytokines, pattern-recognition receptors, and other genes related to immune responses were also observed.
Twenty-four hours post-sepsis induction, bodyweight loss was associated with mortality and organ damage. Importantly, heme significantly reduced mortality from Severe hemolytic disease of the newborn leads to the release of pro-oxidative free heme FH.
Heme oxygenase HO is primarily responsible for detoxifying FH. To investigate the protective effects of HO in a model of heme overload. HO-1 promoter activity was assessed 3, 6, and 24 h after treatment. Cell survival was indexed by viability assays.
LP and AST levels significantly increased Hemopexin levels at baseline were higher in adults compared with newborns for both Wt and Het mice. In addition, FH induced hemopexin levels in both adults and newborns, but to a lesser degree in newborns. FH is highly toxic in vitro, but its toxicity is abolished when bound to albumin. Newborns appear to be protected from the pro-oxidative effects of FH, which may be mediated by heme binding and a higher absolute HO activity at baseline and after FH-mediated induction.
The degree of hyperbilirubinemia and hence risk for developing bilirubin-induced neurologic dysfunction or BIND is dependent upon two major processes: i bilirubin production and its elimination.
RESULTS: In newborns, an increased bilirubin production rate due to hemolysis is often the primary cause of hyperbilirubinemia during the first week of life. If undiagnosed or untreated, it may lead to an increased risk for BIND. Therefore, the ability to identify infants with hemolytic disease is important in assessing those at risk for developing BIND. In addition, an infant's genetic profile and bilirubin binding status can also affect their overall capacity to cope with the resultant tissue bilirubin load and affect risk and guide appropriate management strategies.
Preterm birth PTB is the leading cause of neonatal morbidity and mortality. Previous studies have suggested that the maternal vaginal microbiota contributes to the pathophysiology of PTB, but conflicting results in recent years have raised doubts. We profiled the taxonomic composition of 2, vaginal swabs collected prospectively and weekly during gestation using 16S rRNA gene sequencing. Previously proposed associations between PTB and lower Lactobacillus and higher Gardnerella abundances replicated in the low-risk cohort, but not in the high-risk cohort.
High-resolution bioinformatics enabled taxonomic assignment to the species and subspecies levels, revealing that Lactobacillus crispatus was associated with low risk of PTB in both cohorts, while Lactobacillus iners was not, and that a subspecies clade of Gardnerella vaginalis explained the genus association with PTB.
Patterns of cooccurrence between L. We argue that the vaginal microbiota is better represented by the quantitative frequencies of these key taxa than by classifying communities into five community state types.
Our findings extend and corroborate the association between the vaginal microbiota and PTB, demonstrate the benefits of high-resolution statistical bioinformatics in clinical microbiome studies, and suggest that previous conflicting results may reflect the different risk profile of women of black race. Infiltrating myeloid cells in pregnant uteri play critical roles in the establishment of the placenta and maintenance of normal pregnancies. Their recruitment and proliferation are primarily mediated by the interactions of cytokines and chemokines secreted locally with their corresponding receptors.
Heme oxygenase-1 HO-1 has various physiologic properties that contribute to placental vascular development, with deficiencies in HO-1 associated with pregnancy disorders. With the use of BrdU in vivo assays, HO-1 deficiency did not affect cell proliferation or blood cell populations. Early detection of maladaptive processes underlying pregnancy-related pathologies is desirable, as it will enable targeted interventions ahead of clinical manifestations.
The quantitative analysis of plasma proteins features prominently among molecular approaches used to detect deviations from normal pregnancy. However, derivation of proteomic signatures sufficiently predictive of pregnancy-related outcomes has been challenging.
An important obstacle hindering such efforts were limitations in assay technology, which prevented the broad examination of the plasma proteome. The recent availability of a highly-multiplexed platform affording the simultaneous measurement of 1, plasma proteins opens the door for a more explorative approach. The major aim of this study was to examine whether analysis of plasma collected during gestation of term pregnancy would allow identifying a set of proteins that tightly track gestational age.
Establishing precisely-timed plasma proteomic changes during term pregnancy is a critical step in identifying deviations from regular patterns due to fetal and maternal maladaptations. A second aim was to gain insight into functional attributes of identified proteins, and link such attributes to relevant immunological changes. Pregnant women participated in this longitudinal study. In two subsequent subsets of 21 training cohort and 10 validation cohort women, specific blood specimens were collected during the first wks , second wks , and third wks trimesters, and 6 wks post-partum for analysis with a highly-multiplexed aptamer-based platform.
An elastic net algorithm was applied to infer a proteomic model predicting gestational age. A bootstrapping procedure and piece-wise regression analysis was used to extract the minimum number of proteins required for predicting gestational age without compromising predictive power. Gene ontology analysis was applied to infer enrichment of molecular functions among proteins included in the proteomic model. Changes in abundance of proteins with such functions were linked to immune features predictive of gestational age at the time of sampling in pregnancies delivering at term.
The three top ranked proteins were glypican 3, chorionic somatomammotropin hormone, and granulins. Proteins activating the Janus kinase JAK and signal transducer and activator of transcription STAT pathway were enriched in the proteomic model, chorionic somatomammotropin hormone being the top ranked protein.
Abundance of chorionic somatomammotropin hormone strongly correlated with STAT5 signaling activity in CD4 T cells, the endogenous cell-signaling event most predictive of gestational age.
Results indicate that precisely timed changes in the plasma proteome during term pregnancy mirror a "proteomic clock". Importantly, the combined use of several plasma proteins was required for accurate prediction. The exciting promise of such a "clock" is that deviations from its regular chronological profile may assist in the early diagnoses of pregnancy-relate pathologies and point to underlying pathophysiology.
Functional analysis of the proteomic model generated the novel hypothesis that somatomammotropin hormone may critically regulate T-cell function during pregnancy. The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy.
Cell signaling-based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy.
Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukindependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.
To investigate the distribution of known factors for preterm birth PTB by severity of maternal underweight; to investigate the risk-adjusted relation between severity of underweight and PTB, and to assess whether the relation differed by gestational age.
Retrospective cohort study. State of California, USA. Maternally linked hospital and birth certificate records of California deliveries in were analysed. We assessed whether interpregnancy interval IPI length after live birth and after pregnancy termination was associated with preterm birth PTB.
Multiyear birth cohort. Fetal death, birth and infant death certificates in California merged with Office of Statewide Health Planning and Development. One million California live births after live birth and after pregnancy termination.
Logistic regression was used to estimate odds ratios ORs of PTB of weeks of gestation and its subcategories for IPIs after a live birth and after a pregnancy termination. Analyses included women with IPI after live birth, and women with IPI after pregnancy termination with Preterm labor and infections are the leading causes of neonatal deaths worldwide.
During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes.
This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. It also allowed discovery of new properties that distinguish the fetal and maternal immune systems.
This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes.
Relative contributions of increased production [by end-tidal carbon monoxide concentrations ETCOc ] and decreased elimination of bilirubin to predischarge hour-specific total bilirubin TB levels were assessed in healthy late-preterm and term newborns. Secondly, we report predischarge ETCOc ranges to guide clinical management of hyperbilirubinemia. Increased bilirubin production due to hemolysis can lead to neonatal hyperbilirubinemia. Inhibition of heme oxygenase HO , the rate-limiting enzyme in heme catabolism, by metalloporphyrins Mps may be an ideal preventive strategy for neonatal hemolytic disease.
Zinc protoporphyrin ZnPP is a naturally occurring Mp, potent, not phototoxic, with minimal HO-1 upregulation, but is not orally absorbed.
Here, we evaluated the efficacy of ZnPP-Lipid in heme-loaded newborn mice, a model analogous to hemolytic infants. Brain HO activity was not inhibited. ZnPP-Lipid is effective and thus has potential for treating neonatal hyperbilirubinemia due to hemolysis. Heme oxygenase-1 HO-1 , the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli.
Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm AAA development. In addition, heme is known to strongly induce HO-1 expression. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease.
Neonatal biomarkers of inflammation were examined in relation to early neurodevelopment and gait in very-low-birth-weight VLBW preterm children. We hypothesized that preterm infants exposed to higher levels of neonatal inflammation would demonstrate lower scores on Bayley Scales of Infant Toddler Development, 3rd ed. Neonatal risk factors examined were GA at birth, BW, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, sepsis, and serum C-reactive protein CRP , albumin, and total bilirubin over first 2 postnatal weeks.
Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin.
However, its relative safety and efficacy as compared with conventional phototherapy are unknown. We conducted a randomized, controlled noninferiority trial in which filtered sunlight was compared with conventional phototherapy for the treatment of hyperbilirubinemia in term and late-preterm neonates in a large, urban Nigerian maternity hospital.
The primary end point was efficacy, which was defined as a rate of increase in total serum bilirubin of less than 0. The need for an exchange transfusion was a secondary end point. We also assessed safety, which was defined as the absence of the need to withdraw therapy because of hyperthermia, hypothermia, dehydration, or sunburn.
We enrolled infants and randomly assigned to filtered sunlight and to conventional phototherapy. Single-cell technologies have immense potential to shed light on molecular and biological processes that drive human diseases.
Mass cytometry or Cytometry by Time Of Flight mass spectrometry, CyTOF has already been employed in clinical studies to comprehensively survey patients' circulating immune system. As interest in the "bedside" application of mass cytometry is growing, the delineation of relevant methodological issues is called for.
This report uses a newly generated dataset to discuss important methodological considerations when mass cytometry is implemented in a clinical study. Specifically, the use of whole blood samples versus peripheral blood mononuclear cells PBMCs , design of mass-tagged antibody panels, technical and analytical implications of sample barcoding, and application of traditional and unsupervised approaches to analyze high-dimensional mass cytometry datasets are discussed.
A mass cytometry assay was implemented in a cross-sectional study of 19 women with a history of term or preterm birth to determine whether immune traits in peripheral blood differentiate the two groups in the absence of pregnancy. Twenty-seven phenotypic and 11 intracellular markers were simultaneously analyzed in whole blood samples stimulated with lipopolysaccharide LPS at 0, 0. We assessed the relative contributions of increased bilirubin production indexed by end-tidal carbon monoxide CO concentrations, corrected for ambient CO ETCOc to hour-specific total bilirubin TB levels in healthy late preterm and term newborns.
Spina bifida is the most common form of neural tube defects NTDs. Heme oxygenase HO , the rate-limiting enzyme in heme degradation, has multiple protective properties including mediating antioxidant processes, making it an ideal candidate for study.
However, no study has investigated a possible association between HO-1 genetic polymorphisms and risk of NTDs. This case-control study included spina bifida cases all myelomeningoceles and nonmalformed controls obtained from the California Birth Defects Monitoring Program reflecting births during to Genotype and haplotype frequencies of two HO-1 promoter polymorphisms between cases and controls were compared.
Linkage disequilibrium was observed between the HO-1 polymorphisms D': 0. Although, an association was not found between HO-1 polymorphisms and risk of spina bifida, we speculate that the combined effect of low HO-1 expression and exposures to known environmental oxidative stressors low folate status or diabetes , may overwhelm antioxidant defenses and increase risk of NTDs and warrants further study.
Birth Defects Research Part A , Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete.
We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions.
Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of vaginal specimens from nine women four of whom delivered preterm. Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y.
These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals. Necrotizing enterocolitis NEC , an intestinal inflammatory disease affecting premature infants, is associated with low regulatory T Treg to effector T Teff cell ratios. Controls remained breastfed. HO-1 was induced in WT pups by administering heme preinjury induction.
Lamina propria T cells were identified by flow cytometry. HO-1 can change Treg proportions in the lamina propria of young mice under inflammatory conditions, which might, in part, confer intestinal protection. Maternal obesity is a major source of preventable perinatal morbidity, but studies of the relationship between obesity and preterm birth have been inconsistent. This review looks at two major studies covering just under 3. Inconsistent findings in previous studies appear to stem from the complex relationship between obesity and preterm birth.
Initiatives to decrease maternal obesity represent an important strategy in reducing preterm birth. Zinc protoporphyrin ZnPP is a promising metalloporphyrin with sufficient potency, but has poor solubility and is not absorbed well orally. The use of polymeric particulate delivery systems can improve the stability and enhance intestinal absorption of ZnPP, while retaining HO inhibitory potency without photosensitising effects, and thus is potentially useful in treating neonatal hyperbilirubinemia.
Heme oxygenase HO is the initial, rate-limiting enzyme in the conversion of heme to bilirubin. Dinucleotide GT n repeat length in the promoter region of the encoding gene modulates transcription: shorter alleles, in contrast with longer allele counterparts, are associated with greater gene expression and should result in increased heme catabolism.
We compared the rates of heme catabolism and plasma total bilirubin TB between HO-1 promoter genotypes of varying GT n repeat lengths in glucosephosphate dehydrogenase G6PD -normal and -deficient neonates. HO-1 promoter length was determined from genomic DNA from previous studies by size discrimination of fluorescently-labeled PCR products with capillary electrophoresis. Sizing was confirmed by sequencing homozygote samples. Previously determined values for blood carboxyhemoglobin, corrected for inspired carbon monoxide COHbc , and TB were used to determine the rate of heme catabolism and 3rd day TB values for each HO-1 promoter length genotype, respectively.
In the steady state, HO-1 promoter genotypes, based on the length of GT n repeats, do not modulate heme catabolism or 3rd day TB values in either G6PD-normal or -deficient neonates. This study examined the ability of social, demographic, environmental and health-related factors to explain geographic variability in preterm delivery among black and white women in the US and whether these factors explain black-white disparities in preterm delivery. We examined county-level prevalence of preterm delivery or weeks gestation among singletons born The prevalence of preterm delivery varied two- to three-fold across U.
Much of the geographic variability in preterm delivery in the US can be explained by socioeconomic, demographic and health-related characteristics of the population, but less so for blacks than whites. Pregnancy can be defined as a "permissible" process, where a semi-allogeneic fetus and placenta are allowed to grow and survive within the mother.
Similarly, in tumor growth, antigen-specific malignant cells proliferate and evade into normal tissues of the host. The microenvironments of the placenta and tumors are amazingly comparable, sharing similar mechanisms exploited by fetal or cancer cells with regard to surviving in a hypoxic microenvironment, invading tissues via degradation and vasculogenesis, and escaping host attack through immune privilege.
Heme oxygease-1 HO-1 is a stress-response protein that has antioxidative, anti-apoptotic, pro-angiogenic, and anti-inflammatory properties.
Although a large volume of research has been published in recent years investigating the possible role s of HO-1 in pregnancy and in cancer development, the molecular mechanisms that regulate these "yin-yang" processes have still not been fully elucidated.
Here, we summarize and compare pregnancy and cancer development, focusing primarily on the function of HO-1 in cellular invasion, cytoprotection, angiogenesis, and immunomodulation. Due to the similarities of both processes, a thorough understanding of the molecular mechanisms of each process may reveal and guide the development of new approaches to prevent not only pregnancy disorders; but also, to study cancer. Necrotizing enterocolitis NEC is typified by mucosal destruction, which subsequently can lead to intestinal necrosis.
Prematurity, enteral feeding, and bacterial colonization are the main risk factors and, combined with other stressors, can cause increased intestinal permeability, injury, and an exaggerated inflammatory response.
Heme oxygenase-1 HO-1 mediates intestinal protection due to anti-inflammatory, antioxidative, and antiapoptotic effects of its products carbon monoxide, biliverdin, and bilirubin. This study investigates a possible role of HO-1 in the pathogenesis of NEC using a newborn mouse model.
Control Con pups of both genotypes were dam-fed. Intestines of HO-1 Het Con pups appeared predisposed to injury, with higher histological damage scores, more TUNEL-positive cells, and a significant reduction in muscularis externa thickness compared with Wt Con pups. The increase in HO activity after HO-1 induction by the substrate heme or by hypoxic stress was significantly impaired in HO-1 Het pups.
We conclude that a partial HO-1 deficiency promotes experimental NEC-like intestinal injury, possibly mediated by exaggerated inflammation and disruption in tissue repair.
Medical researchers have called for new forms of translational science that can solve complex medical problems. Mainstream science has made complementary calls for heterogeneous teams of collaborators who conduct transdisciplinary research so as to solve complex social problems. Is transdisciplinary translational science what the medical community needs?
What challenges must the medical community overcome to successfully implement this new form of translational science? This article makes several contributions. First, it clarifies the concept of transdisciplinary research and distinguishes it from other forms of collaboration.
Second, it presents an example of a complex medical problem and a concrete effort to solve it through transdisciplinary collaboration: for example, the problem of preterm birth and the March of Dimes effort to form a transdisciplinary research center that synthesizes knowledge on it.
The presentation of this example grounds discussion on new medical research models and reveals potential means by which they can be judged and evaluated. Third, this article identifies the challenges to forming transdisciplines and the practices that overcome them.
Departments, universities and disciplines tend to form intellectual silos and adopt reductionist approaches. Forming a more integrated or 'constructionist' , problem-based science reflective of transdisciplinary research requires the adoption of novel practices to overcome these obstacles.
Transcutaneous bilirubin TcB was measured at 24 hours, with TSB at hours and at 3- to 5- and 7- to day follow-up visits. Clinical risk factors were identified systematically. Predischarge TSB identified the 41 4. Universal implementation of this strategy in the US should improve outcomes of healthy newborns discharged early.
Previous results from our trial of early treatment with continuous positive airway pressure CPAP versus early surfactant treatment in infants showed no significant difference in the outcome of death or bronchopulmonary dysplasia. A lower vs. We now report longer-term results from our prespecified hypotheses. The primary composite outcome for the longer-term analysis was death before assessment at 18 to 22 months or neurodevelopmental impairment at 18 to 22 months of corrected age.
The primary outcome was determined for of enrolled infants Death or neurodevelopmental impairment occurred in Mortality was increased with the lower-oxygen-saturation target We found no significant differences in the composite outcome of death or neurodevelopmental impairment among extremely premature infants randomly assigned to early CPAP or early surfactant administration and to a lower or higher target range of oxygen saturation.
We provide an approach to the use of phototherapy and exchange transfusion in the management of hyperbilirubinemia in preterm infants of View details for DOI Neonatal hyperbilirubinemia arises from increased bilirubin production and decreased bilirubin elimination. Although phototherapy safely and effectively reduces bilirubin levels, recent evidence shows that it has adverse effects.
Therefore, alternative treatments are warranted. Metalloporphyrins, competitive inhibitors of heme oxygenase HO , the rate-limiting enzyme in bilirubin production, effectively reduce bilirubin formation; however, many are photoreactive.
Here, we investigated possible photosensitizing effects of chromium mesoporphyrin CrMP and zinc deuteroporphyrin bis-glycol ZnBG. Phototoxicity of ZnBG was dependent on light source, emission spectrum, and irradiance. Haem oxygenase-1 HO-1 , the rate-limiting enzyme in haem degradation, plays a role in angiogenesis and vasculogenesis and is highly expressed in the placenta.
Deficiencies in HO-1 are associated with several pregnancy disorders, such as recurrent miscarriages and pre-eclampsia. The unique combination of tissue protective, smooth muscle relaxing and angiogenesis regulatory properties makes HO-1 a key player in the maintenance of a healthy pregnancy through a direct effect on placental structural and vascular development, thus affecting foetal development. Metalloporphyrins are structural analogs of heme and their potential use in the management of neonatal hyperbilirubinemia has been the subject of considerable research for more than three decades.
If you are on a rent-to-own structure, your monthly fee typically equals the cost of the CPAP machine divided by the number of rental months. Your insurance provider usually splits this cost with you, and the exact amount you pay depends on your policy.
Bear in mind that if you are required to rent for longer than a year, you may need to pay a second deductible. If your insurance company determines you are not using the machine frequently enough as per your policy, they may stop covering their portion of the machine rental. You must decide if you prefer to pay the full cost of the monthly rental, purchase the machine outright, or stop CPAP treatment altogether. Be aware that if you decide to stop CPAP treatment and decide later that you want to try the treatment again, your insurance company may require you to re-qualify for coverage.
This process involves performing another sleep study to receive a new diagnosis of sleep apnea and another prescription for a CPAP machine. Then there are supplies that need to be replaced over time, including:. The costs for each component vary. Some rental plans may include the cost of replacement equipment, which is something to bear in mind when comparing the cost of buying outright versus going with insurance. Many insurance providers use the Medicare guidelines for replacing equipment:.
However, each provider has its own replacement guidelines. As you adjust to CPAP treatment, you may desire additional accessories for more comfortable sleep and easier travel. There are a number of optional accessories you can purchase for your CPAP machine. These include:. Insurance does not typically cover any products that are considered optional.
Costs for these products can vary depending on the quality. More expensive accessories often come with warranties of 1 to 3 years. First, your doctor must diagnose you with obstructive sleep apnea following an approved laboratory sleep study or an at-home sleep study, and give you a prescription for a CPAP machine.
Then, Medicare covers a week initial period of CPAP therapy for obstructive sleep apnea, as long as you meet the following requirements :. If you fail to meet these requirements, you have to begin the process again. This involves completing another sleep study, either in a lab or at home, and obtaining another prescription from your doctor. Once you meet your Medicare Plan B deductible, Medicare pays for the rental of the machine for 13 months if you use it continually.
Once the 13 months have passed, you own the machine. State Medicaid programs typically follow the same guidelines as Medicare. You need a sleep test, diagnosis of obstructive sleep apnea, and prescription from your doctor. Your AHI must also meet the same requirements as for Medicare:. Coverage continues if your sleep apnea improves with the CPAP treatment. Insurance plans can significantly help defray the cost of a CPAP machine.
However, if your plan has a high deductible, you might be tempted to purchase your CPAP equipment on your own and bypass your insurance. You might be able to find direct-to-supplier CPAP manufacturers with lower prices than those available through your insurance plan, though be sure to check if these devices are approved by the FDA. When making your decision, calculate whether your CPAP equipment is likely to cost more than your deductible, both now and in the long run.
Keep in mind that whether or not you use insurance, medical equipment sellers require a CPAP prescription in order for you to purchase the machine and equipment. This means your doctor still needs to conduct a sleep study to give you a diagnosis. Once you have the prescription, you can choose whether to buy your CPAP equipment outright or go through your insurance plan. When you choose to buy your CPAP equipment without insurance, you can skip the rent-to-own process and own your machine right away.
You also avoid the insurance requirements of treatment compliance. This eliminates the possibility of needing to return your machine and restart the process of getting a sleep test and prescription from your doctor. Another benefit to paying a medical equipment supplier directly is the wider choice of products available to you. When purchasing with an insurance provider, you are restricted to the suppliers that are covered by your insurance.
This limits your coverage options, and you may not get the exact product you desire. Paying for your equipment directly gives you the opportunity to compare products and choose the CPAP equipment you find most suitable. Most insurance plans offer partial coverage for CPAP machines once you meet your deductible. If you have a high deductible under your health insurance policy, you may inadvertently end up covering the full cost of your CPAP machine.
More advanced machines tend to cost more. The cost you pay depends on your insurance coverage. Typically, your deductible applies to essential CPAP equipment, not including optional accessories.
Most providers have replacement schedules for components such as tubes, masks, and filters that indicate how often replacements are covered. If you require more frequent replacements of certain components, those costs may be out of pocket. Most insurance plans cover a portion of the cost of your sleep studies, including studies conducted in a sleep lab or at home.
Typically, you need a referral for a sleep study in order to receive coverage. Your doctor must determine which type of study is right for you. Insurance providers almost always request that you present an obstructive sleep apnea diagnosis before starting coverage for a CPAP machine and related equipment.
To ignite the saber, click the button once or twist the saber hilt or swing the saber. With a top of the line alignment machine and lift we are able to offer front end repair for all. Learn how to make custom wine labels with this quick and easy tutorial. Snoring occurs when structures within the throat vibrate and cause noise. To get started, just give us a call at or stop by one of our locations! In other words, damaging speech is a universal sinone.
Ground floor flat which consist of living area, kitchen, bedroom and bathroom with separate. We make it work. Prior Authorization must be obtained through CareSource starting after the 3rd month rental months What is Tc Scripts.
The physician services related to home sleep testing G, G and G are covered for the purpose of testing a patient for the diagnosis of obstructive sleep apnea if the home sleep testing is reasonable and necessary for the diagnosis of the patient's condition, meets all other Medicare requirements, including use of an approved.
Whether you need assistance getting from one floor to another in your multi-story home or to get in and out of your vehicle safely, there is a lift device available for you. We also want you to be part of your care planning. Users - User Login. Quantity limits and prior authorization requirements are specific. See more ideas about auto repair shop, auto repair,.
Empower Healthcare Solutions believes this will help you reach your life goals. If you choose to go to an "out-of-network" hospital in a non-emergency, you may be required to pay a larger deductible or a greater portion of your bill. Likes: CPAP machines and supplies are considered durable medical equipment. Walk-ins are welcome, but for prompt service, and due to COVID restrictions, please schedule an appointment. Learn More. What is Snoring? Compound Policy: A Reminder and Clarification.
Additional guidance is given below. The Medical Assistance Plans Division at the Georgia Department of Community Health advances the health, wellness and independence of those we serve by providing access to quality, free and low-cost health care coverage.
My CareSource , your personal online account.. Get the most out of your member experience. Medicare does cover CPAP machine therapy if you are diagnosed with sleep apnea. That is correct, but it's not the whole truth. Posts: Register for an account. CareSource also covers many commonly used over-the-counter OTC medications with a written prescription from your doctor. Meet with a respiratory therapist by appointment. Powering on and off make sure it is charged first : To awaken the saber from deep-sleep mode, hold the button for 4 seconds.
My CareSource is a secure online account for CareSource members. DASCO is a family owned company, helping families in need of home medical equipment since COVID vaccines and testing. Visual Function and Acuity Screening Services. Your insurance provider generally will cover emergency department costs or transfer you to an "in-network" hospital if it is safe to do so.
Request equipment repair or replacement. We're here to help make things a little easier. To retract the saber, press and hold the button for 4. We care about YOU. Since CPAP is the most common form of sleep apnea therapy, it's generally covered by most insurance policies. CPAP is "considered to be durable medical equipment," writes Dr. Helene A. UnitedHealthcare, the nation's largest private insurer, states that it covers nebulizers for asthma and COPD under its Medicare Advantage plans.
UnitedHealthcare says that it covers nebulizers in cases. See reviews, photos, directions, phone numbers and more. For example, Medicaid is more likely to pay for Lap-Band surgery Laparoscopic Adjustable Gastric Banding because this weight loss procedure typically costs less than other treatment alternatives.
Sign Me Up! If you have a Medicare Advantage Plan, you may discover that you have coverage for exercise plans and gyms, but you will need to ask your provider. BMI of 50, 40 with at least one co-morbidity, or under 40 with 2 co-morbidities. If you have been formally diagnosed with sleep apnea, you are likely eligible for a 3-month trial of CPAP therapy.
I had mine done on August 26, Procedure code and Description. View the benefits you have as a CareSource member at-a-glance here. Call your insurance company to find out your. Prior authorization must be obtain through CareSource starting after the 3 rd month rental months Making your health and wellness a priority can be a challenge. Get your CPAP mask fitted.
Tenancy info2, pcm pw 2 bedroom flat to rent St. John's Avenue, London. Last Updated: February 15, If the machine helps, Medicare will continue to pay a share of the machine rental for 13 months, as long as you use it continuously, and after 13 months you own the machine.
Enrollees receive services through either managed.
Can 7 machine-to-machine. Click compliance: policy on. The next uses a months.