Non-Nutritive Sweeteners in Human Amniotic Fluid and Cord Blood: Evidence of Transplacental Fetal Exposure

2021 ◽  
Author(s):  
Brianna C. Halasa ◽  
Allison C. Sylvetsky ◽  
Ellen M. Conway ◽  
Eileen L. Shouppe ◽  
Mary F. Walter ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Cord Blood ◽  
Fetal Exposure ◽  
Third Trimester ◽  
Blood Samples ◽  
Cesarean Birth ◽  
Key Points ◽  
Elective Cesarean ◽  
The Impact

Objective This study aimed to investigate human fetal exposure to non-nutritive sweeteners (NNS) by analyzing amniotic fluid and umbilical cord blood. Study Design Concentrations of four NNS (acesulfame-potassium [ace-K], saccharin, steviol glucuronide, and sucralose) were measured in amniotic fluid (n = 13) and cord blood samples (n = 15) using liquid chromatography-mass spectrometry. Amniotic fluid samples were obtained for research purposes at the time of term elective cesarean birth or clinically indicated third trimester amnioreduction at Mercy Hospital for Women (Melbourne, Australia). All except four women were in the fasting state. Cord blood samples were obtained from an independent cohort of newborns whose mothers were enrolled in a separate clinical trial at the National Institutes of Health. Results Ten of 13 amniotic fluid samples contained at least one NNS (ace-K, saccharin, steviol glucuronide, and/or sucralose). Maximum amniotic fluid NNS concentrations of ace-K, saccharin, steviol glucuronide, and sucralose were 78.9, 55.9, 93.5, and 30.6 ng/mL, respectively. Ace-K and saccharin were present in 100% and 80% of the cord blood samples, with maximal concentrations of 6.5 and 2.7 ng/mL, respectively. Sucralose was not detected and steviol glucuronide was not measurable in any of the cord blood samples. Conclusion Our results provide evidence of human transplacental transmission of NNS. Based on results predominantly obtained from rodent models, we speculate that NNS exposure may adversely influence the offsprings' metabolic health. Well-designed, prospective clinical trials are necessary to understand the impact of NNS intake during pregnancy on human development and long-term health. Key Points

scholarly journals Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

2014 ◽  
Vol 58 (6) ◽  
pp. 3504-3513 ◽  
Author(s):  
Mohammed H. Elkomy ◽  
Pervez Sultan ◽  
David R. Drover ◽  
Ekaterina Epshtein ◽  
Jeffery L. Galinkin ◽  
...  
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Cesarean Delivery ◽  
Plasma Concentrations ◽  
Maternal Blood ◽  
Blood Samples ◽  
Elective Cesarean ◽  
Neonatal Blood ◽  
The Impact ◽  
Maternal Administration

ABSTRACTThe objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.

scholarly journals Effects of Cryopreservation Duration on the Outcome of Single-Unit Cord Blood Transplantation

2018 ◽  
Vol 27 (3) ◽  
pp. 515-519 ◽  
Author(s):  
Tang-Her Jaing ◽  
Shih-Hsiang Chen ◽  
Yu-Chuan Wen ◽  
Tsung-Yen Chang ◽  
Ya-Chun Yang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Clinical Outcomes ◽  
Progenitor Cell ◽  
Cell Function ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
The Impact ◽  
Transplantation Outcomes ◽  
Neutrophil Engraftment

Cryopreservation is widely used in umbilical cord blood (UCB) banking, yet its impact on progenitor cell function remains largely unaddressed. It is unknown whether long-term cryopreservation affects UCB transplantation outcomes. Herein, we evaluated the impact of UCB age on clinical outcomes and investigated the effect of cryopreservation duration of UCB on hematopoietic potency in 91 patients receiving single cord blood transplantations. UCB cryopreservation duration was 0.7 to 13.4 y. The most common indication of transplant was thalassemia (48%). There was no significant association between cryopreservation duration and neutrophil engraftment probability ( P = 0.475). Cryopreservation duration did not affect the post-thaw viability and subsequent neutrophil engraftment rate. Therefore, UCB units can undergo cryopreservation for at least 8 y with no impact on clinical outcomes.

scholarly journals Determinants and Measurement of Neonatal Vitamin D: Overestimation of 25(OH)D in Cord Blood Using CLIA Assay Technology

2019 ◽  
Vol 105 (4) ◽  
pp. e1085-e1092
Author(s):  
Mengdi Lu ◽  
Bruce W Hollis ◽  
Vincent J Carey ◽  
Nancy Laranjo ◽  
Ravinder J Singh ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cord Blood ◽  
Late Pregnancy ◽  
First Trimester ◽  
Controlled Study ◽  
Positive Bias ◽  
Third Trimester ◽  
Serum Samples ◽  
Human Cord Blood ◽  
Blood Samples

Abstract Context Vitamin D (VD) deficiency in pregnancy and the neonatal period has impacts on childhood outcomes. Maternal VD sufficiency is crucial for sufficiency in the neonate, though the effect of early versus late pregnancy 25-hydroxy-vitamin D (25(OH)D) levels on neonatal levels is unknown. Furthermore, chemiluminescence immunoassays (CLIAs) are widely used, though their validity in measuring 25(OH)D specifically in cord blood specimens has not been established. Objective To assess the validity of a CLIA in the measurement of cord blood 25(OH)D and to evaluate maternal determinants of neonatal 25(OH)D, including early versus late pregnancy 25(OH)D levels. Design This is an ancillary analysis from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized, double-blinded, placebo-controlled study. Participants and Intervention A total of 881 pregnant women at high risk of having offspring asthma were randomized to receive VD supplementation or placebo. Serum samples were collected from mothers in early and late pregnancy and from offspring cord blood at birth. 25(OH)D levels were assayed by CLIA in all maternal and offspring samples and by LC-MS/MS in all offspring samples and a subset of 200 maternal third trimester samples. Results Cord blood 25(OH)D levels were higher as measured by CLIA (mean 37.13 ng/mL [SD 18.30]) than by LC-MS/MS (mean 23.54 ng/mL [SD 11.99]), with a mean positive bias of 13.54 ng/mL (SD 12.92) by Bland-Altman analysis. This positive bias in measurement by CLIA was not observed in maternal samples. Third trimester 25(OH)D was a positive determinant of neonatal 25(OH)D levels. Conclusion Chemiluminescence immunoassays overestimate 25(OH)D levels in human cord blood samples, an effect not observed in maternal blood samples. The quantification of 25(OH)D by CLIA should therefore not be considered valid when assayed in cord blood samples. Third trimester, but not first trimester, maternal 25(OH)D is one of several determinants of neonatal 25(OH)D status.

scholarly journals A Case Report to Assess Passive Immunity in a COVID Positive Pregnant Patient

2020 ◽  
Vol 37 (12) ◽  
pp. 1280-1282
Author(s):  
Lorraine E. Toner ◽  
Shari E. Gelber ◽  
Juan A. Pena ◽  
Nathan S. Fox ◽  
Andrei Rebarber
Keyword(s):  
Case Report ◽  
Cord Blood ◽  
Pregnant Patient ◽  
Passive Immunity ◽  
Molecular Testing ◽  
Transplacental Passage ◽  
Blood Samples ◽  
Key Points ◽  
Fetal Cord Blood ◽  
Red Blood Cell Isoimmunization

Introduction Data regarding transplacental passage of maternal coronavirus disease 2019 (COVID-19) antibodies and potential immunity in the newborn is limited. Case Report We present a 25-year-old multigravida with known red blood cell isoimmunization, who was found to be COVID-19 positive at 27 weeks of gestation while undergoing serial periumbilical blood sampling and intrauterine transfusions. Maternal COVID-19 antibody was detected 2 weeks after positive molecular testing. Antibodies were never detected on cord blood samples from two intrauterine fetal cord blood samples as well as neonatal cord blood at the time of delivery. Conclusion This case demonstrates a lack of passive immunity of COVID-19 antibodies from a positive pregnant woman to her fetus, neither in utero nor at the time of birth. Further studies are needed to understand if passage of antibodies can occur and if that can confer passive immunity in the newborn. Key Points

scholarly journals Effects of long-term vaccination against Coxiella burnetii on the fertility of high-producing dairy cows

2015 ◽  
Vol 63 (2) ◽  
pp. 223-233
Author(s):  
Irina Garcia-Ispierto ◽  
Irene López-Helguera ◽  
Joan Tutusaus ◽  
Ramón Mur-Novales ◽  
Fernando López-Gatius
Keyword(s):  
Dairy Cows ◽  
Coxiella Burnetii ◽  
Pregnancy Loss ◽  
Fetal Loss ◽  
Odds Ratios ◽  
Third Trimester ◽  
Final Study ◽  
Study Population ◽  
The Impact

The impact of long-term vaccination against Coxiella burnetii on the fertility of cows was studied. Double vaccinations three weeks apart at the start of the third trimester of gestation in each of two consecutive pregnancies were applied. The final study population consisted of 410 cows after the first vaccination round. Based on the odds ratios, the likelihood of early fetal loss (pregnancy loss following a positive pregnancy diagnosis before Day 90 of gestation) was higher in control cows (OR = 1.42) than in vaccinated cows. The final study population consisted of 336 cows after the second round of vaccination. According to the odds ratios, vaccinated C. burnetii seronegative cows were less likely to be subfertile (> 3 AI) (OR = 0.4) compared to non-vaccinated seronegative animals, and the likelihood of early fetal loss was lower in vaccinated C. burnetii seropositive animals (OR = 0.3) compared to non-vaccinated seronegative cows. Seropositivity to C. burnetii was positively related to twin pregnancy after the two rounds of vaccination (OR = 2.1 and 3.5, respectively). These results indicate that two consecutive vaccination rounds against C. burnetii in advanced gestation reduce subfertility and early fetal loss in dairy cows.

scholarly journals The impact of aging on primate hematopoiesis as interrogated by clonal tracking

Blood ◽  
2018 ◽  
Vol 131 (11) ◽  
pp. 1195-1205 ◽  
Author(s):  
Kyung-Rok Yu ◽  
Diego A. Espinoza ◽  
Chuanfeng Wu ◽  
Lauren Truitt ◽  
Tae-Hoon Shin ◽  
...  
Keyword(s):  
Key Points ◽  
Genetic Barcoding ◽  
The Impact

Key Points Genetic barcoding of HSPCs in aged macaques reveals impaired long-term clonal output from multipotent HSPCs. Aged macaques showed prolonged contributions from lineage-biased HSPCs and late clonal expansions.

Complete Donor T-Cell Chimerism Predicts Lower Relapse Incidence after Standard Double Umbilical Cord Blood Reduced Intensity Conditioning Regimen Allogeneic Transplantation in Adults

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2479-2479
Author(s):  
Pierre Peterlin ◽  
Jacques Delaunay ◽  
Thierry Guillaume ◽  
Thomas Gastinne ◽  
Beatrice Mahe ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning Regimen ◽  
Before And After ◽  
The Impact

Abstract Double umbilical cord blood (dUCB) allogeneic transplantation following low dose TBI, cyclophosphamide and Fludarabine (TCF regimen)-based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there is little data regarding the impact on long-term outcome of CD3+ T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases and who receieved dUCB conditioned with TCF were included in this retrospective study. Peripheral blood CD3+ TCC was considered until day +100 post-tranplant in order to determine the impact of full versus mixed chimerism on long-term outcomes. Twenty-nine and 7 patients were documented with full and mixed CD3+ TCC, respectively, within the first 100 days post-transplant. With a median follow-up of 36 months, 3 year-OS, DFS, and relapse incidence were 61%, (95% CI 43-75); 50% (95% CI 32.5-66) and 28% (95% CI 16-44), respectively. In univariate analysis, a full CD3+ TCC was associated with a better 3-year DFS : 59% (95% CI 39-75.5) versus 14% (95% CI 7-46), (HR=0.24 [0.09-0.65], p=0.005) and a lower cumulative incidence of relapse : 24% (95% CI 21.5-57) versus 78% (95% CI 52-99), (HR=0.18 [0.05-0.5], p=0.004). In multivariate analysis, a full CD3+ TCC remained associated with a lower incidence or relapse (HR=0.17, 95% CI 0.028-0.99, p=0.049). CD3+ TCC has no impact on GVHD and NRM in this study. In conclusion, in our study, full CD3+ TCC was independently associated with a lower risk of relapse after dUCB TCF RIC allogeneic transplant in adults, highlighting the need to develop immunotherapy approaches allowing for early conversion to full chimerism after dUCB. Abstract 2479. Table 1 Patients, sustained cord blood and transplantation characteristics. Patients, sustained cord blood and transplantation characteristics Full TCC (n=29) Mixed TCC (n=7) p No.of patients % No.of patients % Patients characteristic Age at transplant, years, median (range) 57 (22-69) 47 (17-64) NS Sex female 14 48 3 43 NS Hematological malignancy : Lymphoid / myeloid 14 / 15 48 / 52 3 / 4 43 / 57 NS Statut at transplant : RC / RP 23 / 6 79 / 21 6 / 1 86 / 14 NS Time to transplant, days, median (range) 395 (137-5645) 216 (92-604) NS Cord blood characteristics Age of cord blood, months, median (range) 31 (9-165) 116 (23-140) NS Matching cordon with patient NS 4/6 10 35 3 43 5/6 19 65 3 43 6/6 0 0 1 14 Number of total nucleated cell 10^8/kg before and after thawing, respectively, median (range) 0,28 (0,16-0,455) ; 0,248 (0,157-0,406) 0,222 (0,135-0,492) ; 0,22 (0,11-0,392) NS Number of CD34+ cell 10^6/kg before and after thawing, respectively, median (range) 0,066 (0,022-0,215) ; 0,043 (0,02-0,2) 0,078 (0,031-0,427) ; 0,041 (0,019-0,259) NS Mismatch between cord blood and patient Sex 14 48 3 43 NS Serology CMV 13 45 3 43 NS ABO 16 55 2 28 NS Rhesus 22 76 6 86 NS Graft Neutrophil count recovery >0.5 G/L, days, median (range) 17 (6-32) 11 (7-20) NS Platellet recovery >20G/L, days, median (range) 41 (0-164) 31 (0-67) NS Acute GVHD (grade II-IV / grade III-IV) 19 (12 / 6) 65 (41 / 21) 4 (3 / 1) 57 (43 / 14) NS Chronic GVHD (Limited / Extensive) 11 (8 / 3) 38 (28 / 10) 3 (2 / 1) 43 (28 / 14) NS Chimerism Rate, %, median (range) 100 (96-100) 82 (14-94) <0,001 Table 2 Multivariate analysis for DFS, OS and CIR. Multivariate analysis Hazard Ratio 95% CI P values DFS Age (continuos variable) 0.97 0.93 to 1.01 0.174 Sex 0.37 0.10 to 1.26 0.111 TCC full versus mixed 0.28 0.074 to 1.04 0.058 Chronic GVHD : noversus yes 4.68 1.12 to 19.53 0.034 OS Age (continuous variable) 0.95 0.91 to 0.99 0.022 myeloid vs lymphoid 9.13 1.7 to 49.05 0.010 Acute GVHD : none vs grade 3-4 0.24 0.06 to 0.93 0.038 TCC full versus mixed 0.62 0.15 to 2.46 0.495 CIR Age (continuos variable) 0.95 0.91 to 1.00 0.057 Sex 0.88 0.15 to 5.26 0.892 TCC full versus mixed 0.17 0.028 to .99 0.049 Chronic GVHD : no versus yes 8.19 0.46 to 146.41 0.153 Disclosures No relevant conflicts of interest to declare.

A Rapid Qualitative Appraisal of the Impact of COVID-19 on Long-term Care Communities in the United States: Perspectives from Area Aging Staff and Advocates

2020 ◽  
Vol 79 (4) ◽  
pp. 313-322
Author(s):  
Andrea Freidus ◽  
Dena Shenk ◽  
Christin Wolf
Keyword(s):  
Long Term Care ◽  
The United States ◽  
Qualitative Assessment ◽  
Physical And Mental Health ◽  
Term Care ◽  
Care Community ◽  
Care Workers ◽  
Key Points ◽  
The Impact

The COVID-19 epidemic has hit residents and staff of congregate long-term care communities particularly hard. In North Carolina, the site of this research, over half of registered mortality has been associated with congregate living communities. This article reports on phase one of a rapid qualitative assessment of long-term care professionals and regional aging staff navigating care during this epidemic. Our purpose is twofold. We demonstrate both the value of rapid qualitative appraisals to capture the perspectives and concerns of COVID-19’s long-term care workers and area aging staff, in this case, the staff and advocates that care for and protect the rights of long-term care community residents as well as present data collected in this phase. Key points raised focus on safety, including access and use of personal protective equipment, infection control, limited testing, and staffing issues. In addition, participants expressed concerns about the physical and mental health of residents because they have been isolated from family and friends since the executive order closed these communities to all non-essential people. We will utilize these data, in collaboration with staff and advocates, to inform policy and programming to better address the needs of both residents and staff of long-term care communities.

Plasma corticotropin-releasing hormone, β-endorphin and cortisol inter-relationships during human pregnancy

1993 ◽  
Vol 128 (4) ◽  
pp. 339-344 ◽  
Author(s):  
Eng-Cheng Chan ◽  
Roger Smith ◽  
Terry Lewin ◽  
Max W Brinsmead ◽  
Hong-Ping Zhang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Maternal Plasma ◽  
Corticotropin Releasing Hormone ◽  
Third Trimester ◽  
Blood Samples ◽  
Releasing Hormone ◽  
Human Pregnancy ◽  
The Third ◽  
Dynamic Relationships

To investigate the dynamic relationships among corticotropin-releasing hormone (CRH), β-endorphin (βEP), cortisol and obstetric events during pregnancy, blood samples were collected from 193 women at 28 weeks, 38 weeks, during labour and on the second postnatal day. Cord blood at delivery was also obtained. We found that: (1) Maternal plasma CRH, βEP and cortisol rose from 28 to 38 weeks. (2) During the third trimester maternal plasma CRH and βEP were correlated (r=0.30, p<0.001). (3) During labour, no correlations were found among maternal plasma CRH, βEP and cortisol. (4) Maternal CRH at labour and the duration of labour were not correlated. (5) Maternal plasma CRH tended to be higher in women who delivered early (more than seven days prior to estimated date of confinement [EDC]) relative to those who were on time (within seven days' EDC) or late (greater than seven days after EDC). (6) CRH in maternal plasma at labour and cord blood were correlated (r = 0.29, p<0.05) as were maternal and fetal βEP (r=0.43, p<0.001). (7) Fetal obstetric difficulty was correlated with fetal βEP (r=0.54, p<0.001). Our findings support the hypothesis that maternal plasma CRH regulates maternal βEP during the third trimester, but other factors are involved during labour and in response to maternal obstetric stress.

scholarly journals SUN-055 Prenatal Exposure to Artificial Sweeteners

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Brianna C Halasa ◽  
Allison Sylvetsky ◽  
Ellen M Conway ◽  
Peter J Walter ◽  
Hongyi Cai ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Amniotic Fluid ◽  
Cord Blood ◽  
Positive Association ◽  
Taste Preference ◽  
Sweet Taste ◽  
Intestinal Microbiome ◽  
Fasting State ◽  
Blood Samples ◽  
Pregnancy And Lactation

Abstract Introduction: In adults, epidemiologic studies consistently show negative health outcomes (e.g. insulin resistance, stroke) related to artificial (or non-nutritive) sweetener (NNS) intake. In children, NNS sweetened beverage consumption is associated with higher total energy and sugar intake. In infants, we documented the immediate appearance of NNS in breast milk after mothers consume diet soda. A positive association between prenatal NNS exposure and higher BMI at 1 year of life has been observed in infants whose mothers routinely consumed NNS during pregnancy. In mice, we recently reported marked changes in intestinal microbiome and hepatic detoxification pathways of pups that had been exposed to NNS via their mothers’ intake during pregnancy and lactation. Thus, we conducted a pilot project to determine whether there is direct evidence for prenatal NNS exposure in humans. In future studies, we will investigate effects on health outcomes. Methods: Concentrations of 3 NNS (acesulfame-potassium (ace-K), sucralose and saccharin) were measured with liquid chromatography-mass spectrometry in cord blood samples (n=15) and amniotic fluid samples (n=13). Aspartame cannot be measured because of its prompt metabolism into aspartic acid and phenylalanine. The cord blood samples were obtained from offspring of women enrolled in a sickle cell clinical trial at the NIH, while the amniotic fluid samples had been obtained for clinical purposes during the 3rd trimester. No dietary information was available other than 2 of 13 women were not in the fasting state when undergoing amniocentesis. Results: In the cord blood samples, ace-K and saccharin were present in 12/15 (80%) samples. None of the samples contained sucralose. In the 13 amniotic fluid samples, 10 (77%) samples contained at least one sweetener. One sample was positive for all 3 sweeteners. Maximum concentrations in cord blood were 6.5 ng/mL for ace-K and 2.7 ng/mL for saccharin, while maximum concentrations in amniotic fluid were 78.9 ng/mL for ace-K, 55.9 ng/mL for saccharin, and 30.6 ng/mL for sucralose (non-fasting sample). Most women were in the fasting state before undergoing amniocentesis or giving birth, thus NNS peak concentrations could not be determined in this pilot study. Discussion and Conclusion: 80% of cord blood samples (babies’ blood) and 77% of amniotic fluid samples (reflecting babies’ direct gastrointestinal/lung exposure) contained ace-K, saccharin and/or sucralose. We speculate that NNS exposure may influence in utero growth and development, e.g. sweet taste preference and metabolic pathways. Prospective studies are necessary to test these hypotheses. Results will determine whether current recommendations (or lack thereof) regarding NNS intake during pregnancy and lactation need to be revised.

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