Umbilical Cord Blood Samples Research Articles

Characteristics of Pregnant Women and Risk Factors of Their Newborn for Admission to a Neonatal Intensive Care Unit in Nepal.

Nepal has progressed gradually in reducing under-5 mortality and neonatal mortality; however, they are still high at 30.8 and 19.8 per 1000 live births, respectively. Neonatal mortality constituted about 64% of the under-5 mortality in 2019, higher than the global average of 47%. This is a prospective study among pregnant women and their newborn babies in Siddhi Memorial Hospital, Bhaktapur, Nepal, from October 2017 to April 2018. Demographic and clinical data, high vaginal swabs of pregnant mothers, and umbilical cord blood were collected. High vaginal swabs were cultured, and umbilical cord blood samples were cultured and tested for inflammatory markers. After discharge to home, neonates were followed for 28 days of life by weekly phone calls. Total number of pregnant mothers enrolled was 151. The median age was 26 years (IQR: 18-40), and the proportion of adolescent mothers was 4.7%. Half of the deliveries were done by the caesarian section, and 8.6% had gestational age <37 weeks. High vaginal swab cultures were positive in 8.2% of the samples (n=135), and Escherichia coli was the most common bacteria. Out of 153 newborn babies (2 were twins), 8 (5.2%) were admitted to the neonatal intensive care unit. The proportion of low birth weight was 13%, and it was independently associated with neonatal intensive care unit admission (adjusted OR=9.4, 95%CI 1.8-50.1; P value= 0.009). Adolescent pregnancies and Low Birth Weight babies were commonly observed. Both of these issues need to be addressed by effective measures that would improve the current situation of maternal and child health in Nepal.

A method of large DNA fragment enrichment for nanopore sequencing in region 22q11.2.

Background: 22q11.2 deletion syndrome (22q11.2DS) is a disorder caused when a small part of chromosome 22 is missing. Diagnosis is currently established by the identification of a heterozygous deletion at chromosome 22q11.2 through chromosomal microarray analysis or other genomic analyses. However, more accurate identification of the breakpoint contributes to a clearer understanding of the 22q11.2 deletion syndrome. Methods: In this study, we present a feasible nanopore sequencing method of 22q11.2 deletion. This DNA enrichment method-region-specific amplification (RSA)-is able to analyze the 22q11.2 deletion by specific amplification of an approximately 1-Mb region where the breakpoint might exist. RSA introduces universal primers into the target region DNA by a Y-shaped adaptor ligation and a single primer extension. The enriched products, completed by amplification with universal primers, are then processed by standard ONT ligation sequencing protocols. Results: RSA is able to deliver adequate coverage (>98%) and comparable long reads (average length >1Kb) throughout the 22q11.2 region. The long nanopore sequencing reads, derived from three umbilical cord blood samples, have facilitated the identification of the breakpoint of the 22q11.2 deletion, as well as by Sanger sequencing. Conclusion: The Oxford Nanopore MinION sequencer can use RSA to sequence the target region 22q11.2; this method could also be used for other hard-to-sequence parts of the genome.

Hematological Parameters in Newborns of Mothers with and Without Preeclampsia

Background: Pregnancy-induced hypertension, preeclampsia, and eclampsia syndrome are multisystem disorders associated with adaptive changes in the fetal circulation and cause a marked imbalance in the hemostatic system of the mother and fetus. Objectives: This study aimed to compare hematological parameters in newborns of mothers with and without preeclampsia. Methods: This prospective case-control study included 30 newborns of mothers with preeclampsia and 30 newborns with normotensive mothers matched for age and sex as a control group. Umbilical cord blood samples were collected from all newborns, and complete blood count and ferritin levels were measured. The data were analyzed using SPSS version 21, and the difference between the two groups was compared using the independent t-test and Mann-Whitney test. Results: The newborns of mothers with preeclampsia had higher mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, mean platelet volume, and platelet distribution width but lower white blood cell counts, platelet counts, and ferritin level than those of the control group (P &lt; 0.05). Also, the mean red blood cell count, hemoglobin, and hematocrit was higher in the preeclamptic mothers’ newborns compared to those of the control group, although not significant (P &gt; 0.05). Conclusions: Newborns of mothers with preeclampsia should be carefully evaluated and monitored regarding hematologic abnormalities and early diagnosis of possible complications.

The association between gestational diabetes mellitus and DNA damage in umbilical cord leukocytes and placental samples

Objective(s): To evaluate the relation between gestational diabetes mellitus (GDM) and maternal and/or fetal DNA integrity. Method: 59 pregnant women were classified into two groups on the basis of 75 g oral glucose tolerance test (OGTT) and glycemic profile (GP): Control group (OGTT and GP normal, n = 29) and GDM group (abnormal 75 g OGTT, n = 30). The umbilical cord blood and placental samples obtained from the maternal side were collected at the time of delivery. Alkaline comet assay was performed for the determination of DNA damage. The trial was approved with the protocol number 72867572.050.01.04-299082. Result(s): Body mass index (BMI), weight gain during pregnancy, glycemic means and fetal weight were increased in GDM group compared control group (p = .01, .0001, .04, and .01, respectively). In the GDM group, the number of large-for-gestational-age (LGA) infants was significantly higher compared to the nondiabetic group (p = .04). Tail DNA percentages in placental samples were higher in the GDM group compared to controls (p = .01); however, DNA integrity in umbilical cord leukocytes was similar between the groups (p = 0.1). In contrast to umbilical cord DNA damage, placental DNA damage showed positive correlation with maternal glycemia in the whole group and within each group. The positive association of placental DNA damage and GDM remained after adjusting for age, BMI, smoking, glycemia, gestational age at delivery, fetal weight at delivery, and delivery type (p = .01). Conclusion(s): Placental DNA damage is associated with GDM and placental cells seem to be more vulnerable to DNA damage compared to fetal blood cells.

Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against Toxoplasma gondii.

In order to evaluate and compare the specific immune response of pregnant women (PW) chronically infected with Toxoplasma gondii, with and without gestational diabetes mellitus (GDM), and the humoral response of their respective newborns (NB), the study was carried out on 81 PW (34 GDM and 47 controls) from whose medical records the results of the oral glucose tolerance test (OGTT) were obtained, and blood samples were collected at the third trimester of pregnancy; also, on 45 NBs (20 GDM and 25 controls) from whom umbilical cord blood samples were obtained. Humoral immunity was analyzed by measuring anti-T. gondii total IgG, IgG subclasses and IgG avidity. To evaluate cellular immunity, peripheral blood mononuclear cells (PBMC) from 32 PW (16 GDM and 16 controls) were cultured, supernatant cytokines were determined, and flow cytometry was performed to analyze the expression at lymphocytes of surface molecules, cytokines and transcription factors. All PW and NBs were positive for total IgG, and the prevalent subclass was IgG1. There was a negative correlation between the OGTT glycemia of PW and the levels of total IgG, IgG1 and IgG avidity. The IgG avidity of the GDM group was significantly lower than the control group. Patients from the GDM group had a higher number of T lymphocytes expressing markers of cell activation and exhaustion (CD28 and PD-1). In the presence of T. gondii soluble antigen (STAg) the amount of CD4+ T cells producing IFN-γ, IL-10 and IL-17 was significantly lower in the GDM group, while there was no difference between groups in the number of CD4+ CD25HighFOXP3+LAP+ functional Treg cells. Additionally, under STAg stimulus, the secretion of IL-17, IL-4, TNF and IL-2 cytokines at PBMCs culture supernatant was lower in the GDM group. In conclusion, there was a correlation between the increase in blood glucose and the decrease in levels of anti-T. gondii antibodies, associated with the decreased IgG avidity in patients who develop GDM. Also, the GDM group had decreased immune responses in Th1, Th2 and Th17 profiles, suggesting an association between GDM and the negative modulation of the humoral and cellular immune responses against T. gondii.

Distribution of Presepsin, Krebs von den Lungen 6, and Surfactant Protein A in Umbilical Cord Blood.

Presepsin is an early indicator of infection, and Krebs von den Lungen 6 (KL-6) and Surfactant Protein A (SP-A) are related to the pathogenesis of pulmonary infection and fibrosis. This study aimed to establish reference intervals (RIs) of presepsin, KL-6, and SP-A levels and to evaluate the possible influence of neonatal and maternal factors on presepsin, KL-6, and SP-A levels in umbilical cord blood (UCB). Among a total of 613 UCB samples, the outliers were removed. The RIs for presepsin, KL-6, and SP-A levels were defined using non-parametric percentile methods according to the Clinical and Laboratory Standards Institute guidelines (EP28-A3C). These levels were analyzed according to neonatal and maternal factors: neonatal sex, gestational age (GA), birth weight (BW), Apgar score, delivery mode, the presence of premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), and pre-eclampsia. Presepsin, KL-6, and SP-A levels showed non-parametric distributions and left-skewed histograms. The RIs of presepsin, KL-6, and SP-A levels were 64.9–428.3 pg/mL, 43.0–172.0 U/mL, and 2.1–36.1 ng/mL, respectively. Presepsin, KL-6, and SP-A levels did not show significant differences according to sex, GA, BW, Apgar score, delivery mode, PROM, GDM, and pre-eclampsia. The median level and 97.5th centile RI of KL-6 showed a slight increase with increased GA. We established RIs for presepsin, KL-6, and SP-A levels in large-scaled UCB samples. Further investigation would be needed to determine the clinical significance.

Abstract 22 CellStor Transfer Freezing Bag: Reliable Closed System for Complex Cord Blood Sample Processing and CD34+ Hematopoietic Stem Cell Cryopreservation

IntroductionHematopoietic stem cell (HSC) transplants are effective in the treatment of numerous disorders. Proper processing and storage of umbilical cord blood (UCB) and peripheral blood (PB) HSCs is invaluable for therapeutic applications. Although automated sample processing methods exist, they are unable to accommodate low volume, viscous, fibrin clotted, partially hemolyzed, or otherwise complex samples, resulting in the loss of precious HSCs. The CellBios single-use transfer freezing bag was designed to process peripheral and cord blood samples and freeze HSCs, including from those with the above-mentioned problems. Here we demonstrate the utility of these transfer freezing bags to salvage problematic UCB samples and recover precious HSC material suitable for banking and therapeutics.ObjectiveThe objective of this study was to develop a closed UCB sample processing and cryopreservation solution that is amenable to easy manual operation, can deliver excellent HSC viability and recovery, can eliminate contaminating red blood cells (RBCs), and is capable of processing complex/defective starting samples that are incompatible with conventional automated processing systems into therapeutic grade HSC banks.MethodsWe studied 100 randomly selected UCB samples, from various centers throughout India, that were processed and prepared for cryopreservation using our transfer freezing bag. We recorded the pre- and post-sample processing volumes, total nucleated cell counts (TNCC), hematocrit (HCT), CD34+ cell viability, and recovery.ResultsStudy results showed the following: 94% vs 98% CD34+ cell viability post processing, 77% vs 85% total mononuclear cell viability, 69% vs 85% TNCC recovery in problematic vs normal samples, respectively. It was possible to achieve low RBC carryover –91% HCT reduction post-processing in normal samples; more importantly, problematic samples also had RBC removal evidenced by HCT reduction of 45%.DiscussionWe have demonstrated efficient removal of RBCs to alleviate post-transplantation issues and maximized CD34+ HSC recovery in both normal and problematic UCB samples. Crucially, it was possible to salvage precious CB HSCs from defective samples that would be lost had they been processed in conventional automated workflows. The CellBios CellStor Transfer Freezing Bag Set offers best in class performance in preparing umbilical cord blood samples for cryostorage.

Seroprevalence of antibodies against to SARS-CoV 2 in umbilical cord blood in two hospital centers in Córdoba and Sucre, Colombia

IntroductionPregnant women continue to be vulnerable to COVID-19, and their immunosuppressed state could put them at greater risk of developing more severe forms of the disease. In Colombia and Latin America, there are few studies on the immune response of the newborn against SARS-CoV-2. AimTo determine the prevalence of SARS-CoV-2 infection in umbilical cord blood in two hospital centers in Córdoba and Sucre. MethodsBetween March and June 2021, a prospective descriptive cross-sectional study was carried out. Two hospitals from the departments of Córdoba and Sucre, located in the Northwest Caribbean area of Colombia, participated. Three hundred sixty umbilical cord blood samples were taken at the two hospitals. A commercial ELISA was performed to detect total IgG, IgM, and IgA antibodies against the N protein of SARS-CoV-2. The ethics committee approved the study of the participating institutions. ResultsOf 3.291 women who gave birth in the hospital centers included in the study, 360 (11%) participated. Complete clinical data were obtained for 223 women. The mean age of the women was 24 years (range, 15–42). 29.4% (106/360) of the umbilical cord samples had total antibodies against SARS-CoV-2. Pregnant women did not have blood samples taken. 58% of the women were asymptomatic. There was no association between umbilical cord samples, clinical, epidemiological characteristics, and serological response to antibodies to SARS-CoV-2 (p > 0.05). ConclusionsThe prevalence of umbilical cord blood samples was 29.4% for total SARS-CoV-2 antibodies. The study provides essential aspects for the epidemiological approach to neonates infected with SARS-CoV-2.

Maternal COVID-19 Disease and COVID-19 Immunization.

AimThis study aimed to evaluate the immune response and vertical transmission of anti-severe acute respiratory syndrome (SARS) antibodies in vaccinated, expectant mothers infected with coronavirus disease 2019 (COVID-19) and to study the sequelae.Study designThis was a retrospective study of pregnant women conducted at Bahrain Defense Force Hospital from March 2021 to September 2021. The study population was divided into two groups: group 1 was vaccinated with Sinopharm or Pfizer/BioNTech during pregnancy and never infected with COVID-19. Group 2 was unvaccinated and had been infected with COVID-19. Immune responses such as anti-nucleocapsid (anti-N) and anti-spike (anti-S) from paired samples of maternal and umbilical cord blood were measured with Elecsys immunoassay (Roche Holding AG: Basel, Switzerland) at the time of delivery. Obstetric complications such as preterm labor, preeclampsia, and stillbirth were assessed. Analysis was performed using SPSS version 26.0 (IBM Corp: Armonk, NY) and Minitab version 18 (Minitab, LLC: State College, PA). A p-value of less than 0.05 was considered statistically significant.ResultsThe study included 90 vaccinated and 90 COVID-19-recovered pregnant women. Matched samples were available for 80 vaccinated and 74 COVID-19-recovered women. Group 1 had significantly higher levels of anti-S for both the mother and the cord blood and a significantly higher transfer ratio of anti-S. Group 2 had higher levels of anti-N. In group 1, the paired sample titer of anti-S had a weak negative correlation with maternal age whereas, in group 2, the mother’s anti-N had a weak positive correlation with age. Antibodies of COVID-19-recovered mothers and cord blood had a moderate negative correlation with gestational age, except for the mother’s anti-N. In group 1, the transfer ratio of anti-N and anti-S had a statistically significant association with gestational age. Preterm delivery had a high prevalence of anti-transfer ratios of <1, and delivery at >37 weeks had a high prevalence of ≥1. In group 2, 90% of preterm deliveries had transfer ratios of anti-S <1. The latency period of the COVID-19 group had a statistically significant association with the antibody transfer ratio. An interval of less than 100 days had a high prevalence in the ratio of <1. An interval of more than 100 days had a high prevalence in the ratio of ≥1. There was no significant latency period in group 1. Group 1 had a 75% prevalence of an anti-S transfer ratio ≥1 with a birth weight of >3500 g; group 2 had no significance in birth weight. We did not find significance in the sequelae of morbidities in either group.ConclusionThe production of the antibody N in the COVID-19-infected and antibody S in the vaccinated pregnant women as well as the vertical transmission of antibodies was efficacious. Significant variation was found regarding maternal age in both groups. The transfer ratio of the antibodies in the vaccinated and COVID-19-recovered women was significantly higher in terms of babies of the vaccinated and the infected population. The transfer ratios were distinct according to the latency period and birth weight of the infants.

Association of Umbilical Cord Serum Oxidative Stress Markers, ADMA and Adiponectin with Adverse Fetal Outcomes in Hypertensive Disorders of Pregnancy

Background: Limited studies are available on fetal oxidative stress and endothelial dysfunction and their association with adverse fetal outcomes in hypertensive disorders of pregnancy (HDP). Method: Umbilical cord blood samples were collected at delivery from 134 pregnant women with HDP and 59 controls. Markers of oxidative stress, endothelial dysfunction and inflammation and adipokines were analyzed. Results were correlated with adverse fetal outcomes. Results: Malondialdehyde, total antioxidant status(TAS), ADMA and hsCRP levels were increased in late and early onset preeclampsia. Adiponectin levels were decreased in early onset preeclampsia. High ADMA levels were positively associated with preterm births and fetal mortality and high TAS, protein carbonyl content(PC), ADMA and low adiponectin levels were positively associated with low birth weight babies. Conclusion: Fetal systemic oxidative stress, endothelial dysfunction and inflammation were altered in early and late onset preeclampsia. High TAS, PC and ADMA levels and low adiponectin levels were positively associated with adverse fetal outcomes in HDP.

Characterization of laboratory coagulation parameters and risk factors for intraventricular hemorrhage in extremely premature neonates

BackgroundExtremely premature neonates have increased risk for bleeding, perhaps the most devastating version of which being intraventricular hemorrhage (IVH). Limited data are available for coagulation parameters in this vulnerable population. ObjectivesWe conducted a prospective cohort study characterizing coagulation laboratory parameters in extremely premature neonates 23–30 weeks gestational age (GA) and determined coagulation parameters and clinical risk factors associated with IVH. Patients/MethodsOne hundred twenty neonates 23–30 weeks GA were enrolled, and umbilical cord blood samples were obtained and processed at the time of birth. Coagulation parameters including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and activity assays for factors II, VII, IX, X, XIII, and XIII subunit A antigen were performed by standard methods. Clinical risk factors were analyzed for association with IVH. ResultsOf the enrolled neonates, 29 (24.2%) experienced IVH. Persistent pulmonary hypertension (PPHN) independently predicted IVH risk with odds ratio (OR) 5.3 (95% confidence interval [CI] 1.1–24.3), P = .0338; and chronic lung disease (CLD) approached significance with OR 2.3 (95% CI 0.9–5.5), P = .0659. Coagulation parameters were evaluated for association with IVH, and there was no significant difference among coagulation tests in neonates with or without IVH or per GA. Reduced factor XIII subunit A showed significant association with death, P = .003. ConclusionsWe present a large, prospective study of laboratory coagulation parameters in extremely premature neonates, including factor X, factor XIII, and factor XIII subunit A not previously described in this population. These findings may impact clinical practice and should encourage additional study in this vulnerable population.

Correlation between Intrapartum Cardiotocogram Findings and Cord Blood pH in Term and Preterm Labors

Background: The purpose of intrapartum fetal monitoring by cardiotocograph (CTG) is to identify early signs of developing hypoxia so that appropriate action can be taken to improve the perinatal outcome. Although CTG findings are well known to monitor the progress of the labor due to the paucity of recommendations, there has always been a clinical dilemma as the term fetuses respond differently than a preterm fetus. However, umbilical cord blood pH can distinguish the infant at high risk for asphyxia and related sequel. Therefore, because of differences in fetal physiology in term and preterm fetuses, CTG findings vary, and hence the validity of CTG to determine fetal acidosis should be different. Aims and Objectives: This study aimed to correlate abnormal intrapartum CTG findings with umbilical cord blood pH in term and preterm labor and thus evaluate the success of CTG in predicting fetal acidosis during labor. Methods: The present study included 210 women in labor (70 preterm and 140 term) with abnormal intrapartum CTG that was classified as per 2015 revised International Federation of Gynecologists and Obstetrician (FIGO) guidelines. Immediately after delivery, 2 ml Umbilical artery cord blood sample was taken in a pre-heparinized syringe for analysis, pH &lt;=7.2 was taken as acidosis and pH &gt;7.2 was taken as normal. The measured data were general maternal characteristics which included gravida status, associated comorbidities, method of induction and character of liquor, the intrapartum CTG tracings recorded, the cord arterial blood pH and the neonatal characteristics such as APGAR score and neonatal outcome. Results: Data from 70 preterm labor was compared with 140 term labor. In this study, 20.9% of the babies had acidosis. Suspicious CTG due to decreased variability were more common in the preterm group than in the term group (21.4% vs. 8.6% p&lt;0.05). Positive predictive value (PPV) of abnormal CTG for fetal acidosis in the preterm group was found to be higher than that in the term group, PPV of pathological CTG being even higher than suspicious CTG. Women with suspicious CTG had 82% less risk of fetal acidosis as compared to pathological CTG. Women with Bradycardia had 5.9 times the risk of fetal acidosis as compared with normal and tachycardia. Conclusion: Abnormal CTG should be managed appropriately without any delay to prevent acidosis and cord blood pH should be done in all labors with abnormal CTG. However, our findings of a higher incidence of lower cord blood pH and suspicious CTG due to decreased variability alone highlight the limitation of criteria currently used for interpretation of CTG in preterm labors.

Mild or Moderate COVID-19 during Pregnancy Does Not Affect the Content of CD34+ Hematopoietic Stem Cells in Umbilical Cord Blood of Newborns

The study included umbilical cord blood samples (n=64) intended for cryogenic storage of hematopoietic stem cells and obtained from patients with a history of mild and moderate forms of COVID-19 during pregnancy. The control group was composed of samples (n=746) obtained from healthy women in labor. A comparative analysis of the volume of cord blood collected, the total leukocyte count, the relative and absolute content of cells with the CD34+/CD45+ phenotype revealed no significant differences between the groups.

Application of the prenatal BACs-on-Beads™ assay for rapid prenatal detection of sex chromosome mosaicism

The prenatal BACs-on-Beads™ (BoBs) assay was introduced for rapid detection of abnormalities of chromosomes 13, 18, 21, X, and Y and specific nine significant microdeletion syndromes. The ability of prenatal BoBs to detect mosaicism ranged from 20 to 40%. However, there have been no prenatal studies of sex chromosome mosaicism in prenatal BoBs. Therefore, the present study was performed with an aim to uncover the detection level of sex chromosome mosaicism that application of prenatal BoBs assay, and then to assess the sensitivity of prenatal BoBs assay, thereby improving the prenatal diagnostic accuracy. A total of 31 samples of amniotic fluid (AF) and umbilical cord blood (UCB) for prenatal diagnosis were collected, and the results were confirmed through karyotyping, single nucleotide polymorphism microarray (SNP-array) and copy number variation sequencing (CNV-seq). 23 cases of sex chromosome mosaicism were prompted abnormal by prenatal BoBs, the minimum detection level of mosaicism was about 6% as detected by karyotype. The overall sensitivity of prenatal BoBs in the detection of sex chromosome mosaicism was 74.2% (23/31). This study evaluated the effectiveness of prenatal BoBs for detecting sex chromosome mosaicism in prenatal diagnosis, and the results will provide valuable information for genetic counseling.

Association between fetal exposure to polycyclic aromatic hydrocarbons and low birth weight: a case-control study in Shenzhen, China.

The potential hazards of polycyclic aromatic hydrocarbons (PAHs) on fetus development have raised widespread concerns in recent years, although current epidemiological findings are conflicting. The aim of this case-control study was to investigate the relationship between PAH concentrations in maternal serum and low birth weight (LBW). A questionnaire survey was conducted among 144 (72 pairs) neonates with normal or LBW and their mothers at four different hospitals in Shenzhen, China. Peripheral blood from primiparas and umbilical cord blood from neonates were collected. Concentrations of PAHs were determined by gas chromatography-mass spectrometry. The detection frequencies of PAHs were relatively higher in the peripheral blood samples, while levels of low molecular weight PAHs were greater than high molecular weight PAHs in both peripheral and umbilical cord blood samples. Phenanthrene was frequently detected in blood samples from the case and control groups. Logistic regression analysis showed that acenaphthene in peripheral blood was positively associated with LBW (p < 0.05). This study found a relationship between exposure to certain PAHs and LBW, although future studies are needed to confirm these results.

Associations between epigenetic age acceleration and infertility.

STUDY QUESTIONIs the use of ART, a proxy for infertility, associated with epigenetic age acceleration?SUMMARY ANSWERThe epigenetic age acceleration measured by Dunedin Pace of Aging methylation (DunedinPoAm) differed significantly between non-ART and ART mothers.WHAT IS KNOWN ALREADYAmong mothers who used ART, epigenetic age acceleration may be associated with low oocyte yield and poor ovarian response. However, the difference in epigenetic age acceleration between non-ART and ART mothers (or even fathers) has not been examined.STUDY DESIGN, SIZE, DURATIONThe Norwegian Mother, Father and Child Cohort Study (MoBa) recruited pregnant women and their partners across Norway at around 18 gestational weeks between 1999 and 2008. Approximately 95 000 mothers, 75 000 fathers and 114 000 children were included. Peripheral blood samples were taken from mothers and fathers at ultrasound appointments or from mothers at childbirth, and umbilical cord blood samples were collected from the newborns at birth.PARTICIPANTS/MATERIALS, SETTING, METHODSAmong the MoBa participants, we selected 1000 couples who conceived by coitus and 894 couples who conceived by IVF (n = 525) or ICSI (n = 369). We measured their DNA methylation (DNAm) levels using the Illumina MethylationEPIC array and calculated epigenetic age acceleration. A linear mixed model was used to examine the differences in five different epigenetic age accelerations between non-ART and ART parents.MAIN RESULTS AND THE ROLE OF CHANCEWe found a significant difference in the epigenetic age acceleration calculated by DunedinPoAm between IVF and non-ART mothers (0.021 years, P-value = 2.89E−06) after adjustment for potential confounders. Further, we detected elevated DunedinPoAm in mothers with tubal factor infertility (0.030 years, P-value = 1.34E−05), ovulation factor (0.023 years, P-value = 0.0018) and unexplained infertility (0.023 years, P-value = 1.39E−04) compared with non-ART mothers. No differences in epigenetic age accelerations between non-ART and ICSI fathers were found. DunedinPoAm also showed stronger associations with smoking, education and parity than the other four epigenetic age accelerations.LIMITATIONS, REASONS FOR CAUTIONWe were not able to determine the directionality of the causal pathway between the epigenetic age accelerations and infertility. Since parents’ peripheral blood samples were collected after conception, we cannot rule out the possibility that the epigenetic profile of ART mothers was influenced by the ART treatment. Hence, the results should be interpreted with caution, and our results might not be generalizable to non-pregnant women.WIDER IMPLICATIONS OF THE FINDINGSA plausible biological mechanism behind the reported association is that IVF mothers could be closer to menopause than non-ART mothers. The pace of decline of the ovarian reserve that eventually leads to menopause varies between females yet, in general, accelerates after the age of 30, and some studies show an increased risk of infertility in females with low ovarian reserve.STUDY FUNDING/COMPETING INTEREST(S)This study was partly funded by the Research Council of Norway (Women’s fertility, project no. 320656) and through its Centres of Excellence Funding Scheme (project no. 262700). M.C.M. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 947684). The authors declare no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

Monitoring Intrapartum Fetal Distress by Cardiotocography &amp; Observe its Relation with Umbilical Cord Blood Sampling &amp; Perinatal Outcome

Background: Cardiotocography (CTG) being a simple noninvasive tool has been used more frequently in recent decades to detect fetal distress &amp; to reduce neonatal mortality &amp;morbidity related to fetal hypoxia. On the other hand, umbilical cord blood gas can be used to detect fetal acidaemia due to fetal distress more accurately. This study aimed to correlate fetal monitoring findings by intrapartum CTG with umbilical cord blood pH &amp; lactate level &amp;test the ability of CTG to predict fetal distress &amp; neonatal outcome. Materials and Methods: This prospective cross-sectional observational study was conducted in the Department of Obstetrics and Gynecology of Chittagong Medical College Hospital, Chattogram, Bangladesh for one year from July 2020 to June 2021. It included 80 term singleton pregnancies in active labour. Intrapartum CTG was taken and classified into normal, suspicious and pathological according to FIGO guidelines of CTG monitoring 2015. Mode of delivery, liquor colour, Apgar scores at 1 and 5 minutes, and admission to the neonatal intensive care unit (NICU), adverse neonatal outcomes were observed. Immediately after delivery of the baby 10 cm of the umbilical cord was clamped doubly and 2-3 ml of umbilical cord arterial blood was taken immediately in a pre-heparinized syringe and sent to a laboratory for assessment of pH and lactate to detect fetal acidosis. Antenatal CTG was correlated to neonatal outcomes and cord blood acidosis by statistical analysis. Results: In this study, 40.0% of the women had normal CTG, 38.8% had suspicious CTG, and 21.2% had pathological CTG. There was a significant worsening of neonatal outcomes across these three groups concerning depressed (&lt;7) Apgar scores at 1 minute (40.6%, 80.6%, and 100%; P&lt;0.001), depressed Apgar scores at 5 minutes (3.1%, 22.6%, and 47.1%; P&lt;0.001), and admission to the NICU (9.4%, 38.6%, and 70.7%; P&lt;0.001). When CTG was pathological or suspicious CTG delivery by LSCS was 5.33 times higher (RR: 5.33; 95% CI: 2.09 -13.63) compared to subjects with normal CTG. There was also a progressive worsening of cord blood pH (7.25±0.05, 7.20±0.06, and 7.13±0.09; P&lt;0.001) and a progressive increase in lactate (3.66±1.01 mmol/l, 4.79±1.61 mmol/l, and 6.63±2.18 mmol/l; P&lt;0.001). Conclusions: It should be concluded that pathological CTG which correlates intrapartum fetal hypoxia with cord blood acidaemia and adverse neonatal outcomes. As cardiotocography is a simple, cost-effective noninvasive tool it can be used to detect fetal distress in labour. Continues CTG monitoring can be offered or recommended in every labour room setting to detect fetal distress &amp; early intervention to prevent neonatal morbidity &amp; mortality.

Presepsin levels in neonatal cord blood are not influenced by maternal SARS-CoV-2 infection.

Coronavirus disease (COVID-19) can present with various symptoms and can involve multiple organs. Women infected during pregnancy have a higher incidence of obstetrical complications and infants born to "positive" mothers may get the infection with different manifestations. Presepsin seems to be a promising sepsis biomarker in adults and neonates. The aim of this study was to assess if presepsin levels in neonatal cord blood could be influenced by maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 119 neonates born from women with a confirmed diagnosis of SARS-CoV-2 infection were enrolled and presepsin levels of cord blood samples were collected. All neonates were tested for SARS-CoV-2 infection at birth and after 48-72h. The median presepsin value in umbilical cord blood samples collected after birth was 455pg/mL. Presepsin levels were not influenced by maternal symptoms of COVID-19, weight for gestational age, or delivery mode, and did not significantly differ between infants with and without adverse neonatal outcomes. Infants hospitalized for more than 5days had a significantly higher presepsin level at birth rather than those discharged up to 4days of life. Three infants with positive nasopharyngeal swab at birth had higher Presepsin levels than two infants tested positive at 48h. This is the first study reporting cord presepsin levels in term and preterm infants born to mothers with COVID-19, that appeared to be not influenced by maternal clinical presentation. However, further studies are needed to explain the mechanisms of P-SEP increase in neonates exposed to perinatal maternal SARS-CoV-2 infection or with an indeterminate/possible SARS-CoV-2 infection in the same neonates.

Humanized Ovarian Cancer Patient-Derived Xenografts for Improved Preclinical Evaluation of Immunotherapies.

Simple SummaryEpithelial ovarian cancer (EOC) is a heterogenous disease and new combination therapies are employed to improve treatment, decrease disease recurrence, and avoid the development of treatment resistance. Immunotherapy has been suggested to boost the immune system and improve the prognosis of EOC patients. However, overall low response rates and missing reliable biomarkers to stratify patients to their best-suited personalized treatment regime hinder the successful implementation. Our aim is to advance the development and characterization of humanized patient-derived xenograft models aiding to unravel the function and interaction of the unique tumor microenvironment and the immune system in EOC. These developed and clinically relevant humanized models of EOC have the potential to test various immune cell-targeting combination therapies and identify mechanisms in heterogenous EOC cohorts to ultimately allow patient stratification.High-grade serous ovarian cancer (HGSOC) has poor prognosis and new treatment modalities are needed. Immunotherapy, with checkpoint inhibitors, have demonstrated limited impact. To evaluate the suitability for immunotherapeutics, contextualized preclinical models are required to secure meaningful clinical translation. Therefore, we developed and characterized humanized patient-derived xenograft (hu PDX) murine models of HGSOC, which were established by orthotopic implantation of tumor cell suspensions and intravenous injection of CD34+ cells isolated from umbilical cord blood samples. The developing human immune system in NSG and NSGS mice was followed longitudinally by flow cytometry and characterized by mass cytometry with a panel of 34 surface markers. Molecular imaging of tumor burden, survival analysis, and characterization of tumor-infiltrating immune cells was performed to assess the treatment response to anti-PD-1 (nivolumab) monotherapy. Successful generation of hu PDX models was achieved. Mice treated with nivolumab showed a decrease in tumor burden, however no significant survival benefit was identified when compared to untreated controls. No correlation was seen between PD-L1 expression and CD8 T cell infiltration and response parameters. As the characterization showed an immune infiltration of predominantly myeloid cells, similar to what is observed in HGSOC patients, the models may have the potential to evaluate the importance of myeloid cell immunomodulation as well.

A Study of Maternal and Umbilical Cord Blood Lead Levels in Pregnant Women.

Lead is a highly toxic element which can cross the placental barrier and enter the fetus during pregnancy. Parental lead exposure has adverse effect on infant as well as on maternal health. As part of our program to investigate the lead poisoning in human population we investigated the maternal blood lead levels (MBLL) and umbilical cord blood lead (UBLL) levels in 200 pregnant women and collected their socio-demographic details. In the study we found high lead levels in both maternal and umbilical cord blood samples. The results showed 47.5% maternal blood (n = 95) detected with lead while 38.5% umbilical cord blood (n = 77) samples had lead concentration higher than that of reference range of ≤ 5µg/dL. We also found that the Spearman's correlation coefficient (rs) revealed a strong positive correlation between the MBLL and UBLL (rs = 0.63). The results from socio-demographic questionnaire demonstrated that the recent home painting (p = 0.002) and residing close proximity to traffic congestion (p = 0.05) were significantly associated with MBLL. Education, mother age, fuel and water sources were not significantly associated with MBLL. Iron and calcium deficiency along with tiredness, lethargy, abdominal pain were also reported in women having high lead level > 5µg/dL. Concludingly, on the basis of results obtained it may be stated that we found elevated BLLs in both pregnant women as well as in umbilical cord blood. The prevalence of elevated lead levels in mothers will expose the fetus to lead through placental barriers mobilization and it can have long term adverse effects on the developing fetus. Therefore, it is recommended that screening of blood lead levels be carried out in high-risk women based on their social, occupational, environmental, and individual factors. In addition, stringent regulations on lead-based products are also required from government agencies/authorities to reduce environmental lead burden and toxicity. Moreover, public awareness programs should be organized on hazardous effect of lead.