Umbilical Cord Samples Research Articles

Amylin peptide levels are raised in infants of diabetic mothers

Background: Amylin is a novel 37 amino acid peptide hormone that is co-secreted with insulin from the pancreas in response to food intake. As a potent inhibitor of gastric emptying...

Serum polychlorinated biphenyl and organochlorine insecticide concentrations in a Faroese birth cohort

A prospective birth cohort of 1022 participants was established in the Faroe Islands over a 21-month period during 1986–1987. We collected questionnaire data on potential persistent organic pollutant (POP) concentration predictors, such as duration of breastfeeding and blubber consumption. To assess the participants’ exposure from in utero to 14 years of age to polychlorinated biphenyls (PCBs) and the insecticide p, p′-DDT and its primary degradate p, p′-DDE, we measured 37 PCB congeners and pesticides in 316 umbilical cord samples taken from participants at birth, in 124 serum samples collected from participants at approximately 7 years of age, and in 795 serum samples collected from participants at 14 years of age. Measurements of higher chlorination PCB congeners made on individuals’ serum samples collected at 7 years and 14 years were highly correlated (typically r > 0.5, p > 0.01), although their concentrations at 7 years were generally two to three times higher than at 14 years. Similarly, umbilical cord PCB concentrations were correlated with PCB concentrations in both 7- and 14-year serum samples. Sex-specific differences in higher chlorination PCB and p, p′-DDE concentrations were found at 14 years but not at 7 years, although a sex interaction with blubber consumption and nursing duration was observed at both ages. Both duration of breastfeeding and consumption of blubber were significant predictors of serum ∑ PCB concentrations at 7 and 14 years. Multivariate analyses showed that breastfeeding duration was the primary contributor to serum ∑ PCB concentrations at 7 years, and blubber consumption was the primary contributor at 14 years. These data suggest that infant exposures from breastfeeding were sufficiently large so that continued exposures to PCBs, p, p′-DDT, and p, p′-DDE through the diet have not fully diluted their contribution to the ∑ PCB and p, p′-DDE body burden of the children.

Kinetic disposition of lorazepam with focus on the glucuronidation capacity, transplacental transfer in parturients and racemization in biological samples

The present study investigates the kinetic disposition with focus on the racemization, glucuronidation capacity and the transplacental transfer of lorazepam in term parturients during labor. The study was conducted on 10 healthy parturients aged 18–37 years with a gestational age of 36–40.1 weeks, treated with a single oral dose of 2 mg racemic lorazepam 2–9 h before delivery. Maternal venous blood and urine samples were obtained over a 0–48 h interval and the umbilical cord sample was obtained immediately after clamping. Lorazepam enantiomers were determined in plasma and urine samples by LC–MS/MS using a Chiralcel ® OD-R column. In vitro racemization of lorazepam required the calculation of the pharmacokinetic parameters as isomeric mixtures. The data were fitted to two-compartment model and the pharmacokinetic parameters are reported as means (95% CI): t 1/2a 3.2 h (2.6–3.7 h), K a 0.23 h −1 (0.19–0.28 h −1), t 1/2 10.4 h (9.4–11.3 h), β 0.068 h −1 (0.061–0.075 h −1), AUC 0–∞ 175.3 (ng h)/ml (145.7–204.8 (ng h)/ml), Cl/F 2.6 ml/(min kg) (2.3–2.9 ml/(min kg)), Vd/F178.8 l (146.5–211.1 l), Fel 0.3% (0.1–0.5%), and Cl R 0.010 ml/(min kg) (0.005–0.015 ml/(min kg)). Placental transfer of lorazepam evaluated as the ratio of vein umbilical/maternal vein plasma concentrations, obtained as an isomeric mixture, was 0.73 (0.52–0.94). Pregnancy changes the pharmacokinetics of lorazepam, with an increase in the apparent distribution volume, an increase in apparent oral clearance, and a reduction of elimination half-life. The increase in oral clearance may indicate an increase in glucuronidation capacity, with a possible reduction in the plasma concentrations of drugs depending on glucuronidation capacity as the major metabolic pathway.

SERUM POLYCHLORINATED BIPHENYL AND ORGANOCHLORINE INSECTICIDE CONCENTRATIONS IN A FAROESE BIRTH COHORT

A prospective birth cohort of 1022 participants was established in the Faroe Islands over a 21-month period during 1986-1987. We collected questionnaire data on potential persistent organic pollutant (POP) concentration predictors, such as duration of breastfeeding and blubber consumption. To assess the participants' exposure from in utero to 14 years of age to polychlorinated biphenyls (PCBs) and the insecticide p,p'-DDT and its primary degradate p,p'-DDE, we measured 37 PCB congeners and pesticides in 316 umbilical cord samples taken from participants at birth, in 124 serum samples collected from participants at approximately 7 years of age, and in 795 serum samples collected from participants at 14 years of age. Measurements of higher chlorination PCB congeners made on individuals' serum samples collected at 7 years and 14 years were highly correlated (typically r > 0.5, p > 0.01), although their concentrations at 7 years were generally two to three times higher than at 14 years. Similarly, umbilical cord PCB concentrations were correlated with PCB concentrations in both 7- and 14-year serum samples. Sex-specific differences in higher chlorination PCB and p,p'-DDE concentrations were found at 14 years but not at 7 years, although a sex interaction with blubber consumption and nursing duration was observed at both ages. Both duration of breastfeeding and consumption of blubber were significant predictors of serum summationPCB concentrations at 7 and 14 years. Multivariate analyses showed that breastfeeding duration was the primary contributor to serum summationPCB concentrations at 7 years, and blubber consumption was the primary contributor at 14 years. These data suggest that infant exposures from breastfeeding were sufficiently large so that continued exposures to PCBs, p,p'-DDT, and p,p'-DDE through the diet have not fully diluted their contribution to the summationPCB and p,p'-DDE body burden of the children.

Micronucleus frequency in human umbilical cord lymphocytes

The human fetus is exposed to a variety of environmental agents and drugs which cross the placenta and can induce DNA damage. Micronucleus (MN) determination is a suitable and sensitive method for measuring DNA damage and since umbilical cord blood is obtained without any risk for the newborn, we measured the frequency of MN in cells from cord blood in four groups of healthy newborns (NB): 35 NB whose mothers lived in two urban cities (groups I and II); 16 NB from an agricultural area (group III); and 15 NB of mothers with high-risk pregnancy (group IV). MN were also evaluated in the mothers of NB from group I ( n = 17) and group III ( n = 14). Acetylcholinesterase (AChE) concentration was measured in groups I and III. The average frequency of binucleated cells with MN was 3.7 ± 1.4 in 1000 cells in mothers and 1 ± 0.9 in 1000 cells in NB from urban areas; and 4.5 ± 2.4 in1000 cells in mothers and 2 ± 1.5 in 1000 cells in NB from the agricultural area. The correlation between the frequency of MN in mothers and NB was significant ( r = 0.61, p < 0.01). AChE levels of samples obtained both from group III mothers and from newborns were similar to those of group I. The Wilcoxon's rank-sum test was applied to measure differences in MN frequency; NB of group I were used as control group. A significant ( p < 0.01) higher frequency of MN (4 ± 2) was found only in lymphocytes from NB from high-risk pregnancies. Data indicate that MN evaluation in umbilical cord samples might be useful in the identification of transplacental mutagens.

Proteomic profiling of human stem cells derived from umbilical cord blood

CD34+ preparations from five different umbilical cord samples were compared with respect to their proteome profile using 2-D gel electrophoresis. Fifty-two protein spots were found to match in all preparations referring to the high heterogeneity of such samples indicating a not fully developed (or instable) proteome of stem cells. All matching spots were subjected to in-gel digestion and nano-LC-MS/MS sequence analysis, from which 22 proteins were unambiguously identified.

Neuronal cell injury precedes brain atrophy in multiple sclerosis

<h3>Introduction</h3> Bacterial vaginosis (BV) and vaginal microbiota disruption during pregnancy are associated with increased risk of spontaneous preterm birth (SPTB), but clinical trials of BV treatment during pregnancy have shown little or no benefit. An alternative hypothesis is that vaginal bacteria present around conception may lead to SPTB by compromising the protective effects of cervical mucus, colonising the endometrial surface before fetal membrane development, and causing low-level inflammation in the decidua, placenta and fetal membranes. This protocol describes a prospective case-cohort study addressing this hypothesis. <h3>Methods and analysis</h3> HIV-seronegative Kenyan women with fertility intent are followed from preconception through pregnancy, delivery and early postpartum. Participants provide monthly vaginal specimens during the preconception period for vaginal microbiota assessment. Estimated date of delivery is determined by last menstrual period and first trimester obstetrical ultrasound. After delivery, a swab is collected from between the fetal membranes. Placenta and umbilical cord samples are collected for histopathology. Broad-range 16S rRNA gene PCR and deep sequencing of preconception vaginal specimens will assess species richness and diversity in women with SPTB versus term delivery. Concentrations of key bacterial species will be compared using quantitative PCR (qPCR). Taxon-directed qPCR will also be used to quantify bacteria from fetal membrane samples and evaluate the association between bacterial concentrations and histopathological evidence of inflammation in the fetal membranes, placenta and umbilical cord. <h3>Ethics and dissemination</h3> This study was approved by ethics committees at Kenyatta National Hospital and the University of Washington. Results will be disseminated to clinicians at study sites and partner institutions, presented at conferences and published in peer-reviewed journals. The findings of this study could shift the paradigm for thinking about the mechanisms linking vaginal microbiota and prematurity by focusing attention on the preconception vaginal microbiota as a mediator of SPTB.

Factor V Leiden Mutation Enhances Thrombin Formation in Healthy Newborn Infants.

Background: At birth, the coagulation system is activated resulting in thrombin formation in the newborn. In sick newborns, the coagulopathy may lead to bleeding or thrombotic complications. Known genetic prothrombotic defects are risk factors for thrombosis in adults but their potential influence on perinatal coagulopathy remains unknown. Accordingly, we prospectively studied the influence of genetic thrombophilia on thrombin formation during the first two weeks of life.Methods: Newborns from 22 pregnant women with thrombophilia (Factor V Leiden (FVL), n=16; anticardiolipin antibodies, n= 3; lupus anticoagulant, n=1; protein C deficiency, n=1; prothrombin G20210A mutation, n=1) were enrolled into the study. All women were treated with low-molecular-weight heparin during pregnancy and all the infants were born at term. Blood samples were collected from the umbilical cord, and on postnatal days 1 and 14. Newborns were screened for FVL and prothrombin G20210A mutation. Eight FVL heterozygotes were found. No infant tested positive for anticardiolipin antibodies or lupus anticoagulant. Thrombin formation was assessed by measuring prothrombin fragment F1+2. For samples on day 1, a previous cohort of 32 newborns (mean gestational age 33.6 weeks, unknown FVL status) treated in our neonatal intensive care unit (NICU) was used as an additional control.Results: Relative to known normal range in adults, enhanced thrombin formation (F1+2>1.1 nM) was detected in cord blood and on day 1 in all newborns followed by near normalization on day 14. The median level of F1+2 from umbilical cord sample to day 1, and to day 14 in FVL negative newborns was 2.4 nM (n=13) − 2.0 nM (n=10) − 2.0 nM (n=12), and in FVL heterozygotes 4.8 nM (n=7) − 5.8 nM (n=5) − 1.7 nM (n=8). In FVL heterozygotes but not in FVL negative newborns the F1+2 decrease from umbilical cord sample to day 14 was significant (Wilcoxon p=0.02). On day 1, the FVL heterozygotes showed elevated F1+2 levels when compared with a cohort of 32 newborns in NICU (median F1+2 2.3 nM in NICU group vs 5.8 nM in FVL heterozygotes; p=0.06).Conclusions: Factor V heterozygosity was associated with transiently enhanced thrombin formation in healthy newborns during the first days of life.

Mesenchymal progenitor cells in the human umbilical cord.

Mesenchymal progenitor or stem cells (MPCs) isolated from fetal blood, liver, and bone marrow are a population of multipotential cells that can proliferate and differentiate into multiple mesodermal tissues including bone, cartilage, muscle, ligament, tendon, fat, and stroma. The objective of this study was to isolate and characterize MPCs in the human umbilical cord. The suspensions of endothelial and subendothelial cells in cord vein were collected and cultured in M199 supplemented with 10% fetal bovine serum (FBS). Of 50 umbilical cord samples, 3 had numerous fibroblastoid cells morphologically distinguishable from endothelial cells. Fibroblastic cells displayed lack of expression of vWF, Flk-1, and PECAM-1, indicating the endothelial cell-specific marker. To investigate the differentiation potentials, the cells were cultured in adipogenic or osteogenic medium for 2 weeks. Fibroblast-like cells treated with adipogenic supplementation showed Oil red O-positive staining and expressed adipsin, FABP4, LPL, and PPARgamma2 genes by reverse transcriptase polymerase chain reaction (RT-PCR). In osteogenic differentiation, alkaline phosphatase activity and calcium accumulation were detected. RT-PCR studies determined that Cx43, osteopontin, and Runx2 genes were expressed in the osteogenic cultures. Among three cell lines cultured continuously for passage 10, two had normal karyotypes; however, one retained a karyotype of mos 46,XY[19]/47,XY,+mar[3]. These observations suggest that MPCs are present in human umbilical cord and possess several typical traits of MPCs.

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30-42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0-6 months and 30-42 months, respectively (n=2,044), and with eczema at 18-30 months (n=2,173), were analysed. Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy. The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.

Low Environmental Contamination by Lead in Pregnant Women: Effect on Calcium Transfer in Human Placental Syncytiotrophoblasts

There is an extensive literature on the neurotoxic effects of lead (Pb) on the developing fetus; however, little is known about the mechanisms of action at low levels. Heavy metals are known to affect calcium (Ca2 + ) homeostasis through perturbation of Ca2 + channels and pumps and interference with protein kinase C (PKC) and Ca2 + binding protein (CaBP). During pregnancy, placental Ca2 + exchange is one of the most important mechanisms for fetal survival. This ion is an essential element for healthy fetal growth and development. The aim of the present study was to determine the influence of low maternal blood Pb levels on Ca2 + levels in serum and placenta and placental Ca2 + transfer. Blood samples (maternal and cord) and placental tissue were obtained at birth from 30 women residing in southwest Quebec. Total 2+and Pb levels were measured in maternal and umbilical cord samples and placental tissue at term. The placentas were taken for trophoblast cell isolation and Ca2 + incorporation kinetic experiments. Data showed that Ca2 + in maternal blood did not influence Ca2 + uptake by syncytiotrophoblast. However, although maternal and cord blood Pb levels were low, maternal blood Pb concentration was significantly linked to a decrease in Ca2 + uptake by syncytiotrophoblast. This suggests that exposure to very levels of Pb significantly modifies Ca2 + transfer in syncytiotrophoblasts.

Randomized controlled trial of misoprostol for second-trimester pregnancy termination associated with fetal malformation

Objective Our purpose was to compare the effectiveness, women's views of the termination procedure, and success of umbilical cord culture for vaginal and oral misoprostol versus intra-amniotic prostaglandin PGF 2α for second-trimester pregnancy termination (STPT). Study design We randomized 217 women, 15 to 24 weeks' gestation, into 3 groups. Oral (OM) and vaginal (VM) misoprostol groups received 400 μg of misoprostol every 4 hours for 24 hours. The intra-amniotic PGF 2α (IAPG) group received 40 mg of PGF 2α followed by oxytocin infusion. Women completed self-administered questionnaires 3 weeks after the termination procedure. Umbilical cord samples were collected at delivery for karyotype analysis. The primary outcome was the time from start of the procedure to placental delivery. Secondary outcomes were maternal complications, women's acceptance of the termination procedure, and success rates of umbilical cord culture. Results The time was longer for the OM group (30.5±14.4 hours) compared with the VM group (18.3±8.2 hours) and the IAPG group (21.1±10.2 hours), P<.001 for both comparisons. Women in the VM group reported being more willing to repeat the termination method in the future and reported fewer side effects than those in the other groups, P<.001. Failure rates for umbilical cord cultures were 9.6%, 17.0%, and 45.6% for the VM, OM, and IAPG groups, respectively. Conclusion Oral misoprostol is less effective than intra-amniotic PGF 2α or vaginal misoprostol for STPT. Women report vaginal misoprostol more acceptable than other methods. Umbilical cord culture failure rate is highest in the IAPG group.

Sonographic morphology and hyaluronan content of umbilical cords of healthy and down syndrome fetuses in early gestation

Objective: To explore the sonographic vascular architecture and the hyaluronan amount and distribution of umbilical cords of healthy and trisomy 21 fetuses in early gestation. Material and methods: Umbilical cord sonographic morphology and morphometry of 112 consecutive normal fetuses and 11 trisomy 21 fetuses were assessed between 10 and 15 weeks of gestation. The umbilical coiling index was defined as the reciprocal of the length of one complete coil measured in a longitudinal section of the umbilical cord. The umbilical coiling angle was defined as the maximum angle between the long axis of the umbilical cord and that of the umbilical arteries. Three umbilical cord samples obtained from Down syndrome fetuses and one from a healthy fetus after voluntary termination of pregnancy at 13 weeks of gestation were used for biochemical analysis. Quantitative hyualuronan content and tissue distribution was studied using fluorophore-assisted carbohydrate electrophoresis (FACE) analysis and staining methods using biotin-labeled hyaluronan-binding protein (bHABP), respectively. Results: A significant correlation was present between gestational age and both the umbilical coiling index ( r=−0.56, p<0.001) and the umbilical coiling angle ( r=−0.43, p<0.001). The proportion of uncoiled umbilical cords was significantly higher in Down syndrome fetuses than in healthy fetuses [8/112 (7.1%) vs. 4/11 (36.4%), p<0.05]. Biochemical analysis demonstrated a higher amount and a different distribution of hyaluronan in trisomy 21 umbilical cords compared to healthy fetuses. Conclusion: The umbilical cord of Down syndrome fetuses in early gestation shows peculiar sonographic vascular features and quantitative alterations of the Wharton's jelly hyaluronan.

KEY ISSUES IN GENETIC EPIDEMIOLOGY: LESSONS FROM A UK BASED EMPIRICAL STUDY

1. Introduction Population-based genetic research aims to study gene-disease associations and genetic polymorphisms. By combining genetic samples (taken from blood or tissue) with medical, genealogical and lifestyle information, researchers hope to better understand disease causation and to develop improved methods of diagnosis and treatment. Such studies are a growing area of international research (Austin, et al 2003). In 2004, the world's largest proposed gene bank, UK BioBank (UKBB), plans to start collecting DNA samples from 500,000 British men and women aged between 45 and 69. As one might expect, however, gene banks raise a number of ethical, legal, and social issues. A key question for policy-makers and practitioners is how to create a climate in which potential health benefits can be realized without harming the interests of donors. In order to be successful, biobanks must achieve high rates of participation. Thus, a central question concerns the acceptability of databases to the public (Lowrance 2001). This paper addresses critical issues in DNA banking by using the UK-based North Cumbria Community Genetics Project (NCCGP) as a case study. The NCCGP was a collaboration between the University of Newcastle and Westlakes Research Institute in north-west England. From January 1996 until April 2003, pregnant women in West Cumbria were informed of the project by their local community mid-wife and were asked to provide written consent prior to giving birth. The NCCGP collected blood and tissue samples from the umbilical cord of newborn babies, maternal blood samples (from 1999) and personal health information derived from questionnaires (Chase et al 1998). The samples were frozen and stored for future use, so that the NCCGP can provide a resource of DNA samples for other researchers to use in genetic epidemiological studies (which so far include investigations on heart disease, breast cancer, and neural tube defects) (1). The NCCGP enjoyed a high response rate. Nearly ten thousand samples were collected, which means that nearly 90% of the pregnant women approached agreed to provide umbilical cord samples and maternal blood specimens (Chase et al 2000). However, only 60% of those approached completed the 'mother's questionnaire' (a health and lifestyle questionnaire for the woman and her partner) as well as donating samples. Such response rates could be thought as curious, given the ethical concerns often raised about DNA banking, such as informed consent, confidentiality and security of data, the potential for misuse and abuse of samples, third party access, feedback to donors (House of Lords 2001). Our study, funded by the Wellcome Trust, sought to compare and contrast the perceptions and attitudes of those who have agreed to donate samples to the North Cumbria Community Genetics Project (NCCGP) with those who have declined. This has provided much needed empirical data to add to normative discussions of why people do and do not donate. It was based on the premise that we know little about the views of those who have actually been asked to donate to a genetic database and that policy-makers and researchers would benefit from an investigation that opened up the 'black box' of the social processes that lie between the request to donate and the collection of samples and information. As well as addressing original questions regarding donation and participation, our research enables us to address a wider set of issues including the nature of 'informed consent', 'altruism', and 'benefit-sharing'. The fieldwork for our study involved semi-structured qualitative interviews with forty-three women who donated tissue samples to the NCCGP, seven who refused, seven NCCGP team members, two members of the NCCGP's Ethics Advisory Group, two focus group discussions involving ten community midwives, and three members of local community groups that opposed the NCCGP when plans for it were first announced in the early 1990s. …

Cardiac troponin I, cardiac troponin T and creatine kinase MB concentrations in umbilical cord blood of healthy term neonates

Aims: To measure and compare cardiac troponin I, cardiac troponin T and creatine kinase MB concentrations in the umbilical cord blood of healthy term infants and to investigate the relationship between maternal and neonatal troponin values at birth. Methods: Troponin I, troponin T and creatine kinase MB concentrations were measured from the umbilical cord samples of 85 healthy term neonates and in the blood samples of their respective mothers at birth. Results: Median (interquartile range) umbilical cord concentrations were 0 μg/L (0–0) for troponin I, 0 μg/L (0–0.019) for troponin T and 4.90 μg/L (3.90–6.61) for creatine kinase MB. Troponin I and T concentrations were higher than the detection limit for the assay in 2 (2.3%) and 41 (48.2%) neonates, respectively. Two mothers (2.3%) had cTnT levels above the detection limit; none of them had increased levels of cTnI. Conclusion: Probably owing to differences in expression and assay detection limits, cord blood troponin T concentrations are frequently over the detection limit at birth, while troponin I is mostly undetectable and comparable with that in healthy pregnant women. These cardiac regulatory proteins are of neonatal origin and are not influenced by maternal levels.

Umbilical Vein and Placental Vessels from Newborns with Hereditary Haemorrhagic Telangiectasia Type 1 Genotype are Normal despite Reduced Expression of Endoglin

Hereditary haemorrhagic telangiectasia, HHT, is an autosomal dominant disorder that affects approximately 1 in 8000 people. HHT1 is associated with mutations in the ENG ( Endoglin) gene and with haploinsufficiency. The disorder is characterized by focally dilated vessels, which can lead to arteriovenous malformations and serious complications even in young children. In the current study, umbilical cord and placenta samples from newborns with ENG mutations were analyzed to estimate the level of corresponding protein and look for potential vascular dysplasia. We confirmed, using metabolic labelling and flow cytometry, that endoglin levels were significantly reduced to median values of 47 per cent (range 32–56 per cent) and 58 per cent (46–90 per cent), respectively, in human umbilical vein endothelial cells derived from newborns with ENG mutations (HHT1 group; n=18) relative to samples from newborns shown not to have the familial mutation (non-HHT group). We also quantified the relative expression of endoglin by estimating the endoglin/PECAM-1 staining ratio in tissue sections. We observed significantly lower values in the HHT1 group, compared to the non-HHT group for the umbilical vein ( n=9; median 0.6 vs 0.9; ranges 0.2–1.0 and 0.5–1.5) and for placental stem villus vessels ( n=9 and 10; median 0.42 vs 0.93; ranges 0.24–0.58 and 0.56–1.18). No differences in the estimated umbilical vein cross-sectional area and in the proportion of vessels present in placental villi were observed in sections from the HHT1 group relative to the non-HHT group. Thus, blood vessels from HHT1 individuals are maintained intact in the umbilical vein and placenta during pregnancy and delivery, despite a significant reduction in endoglin expression.

Fine-needle aspiration in the evaluation of nucleated red blood cells in the human placenta

Objective: The purpose of this study was to evaluate the correlation between placental and umbilical cord nucleated red blood cell counts. Study Design: Eighty placentas and their matched umbilical cord blood samples were collected prospectively immediately after delivery. In vitro fine-needle aspiration biopsy specimens were used to obtain placental tissue samples. Nucleated red blood cells were counted by both manual microscopy and flow cytometry. Statistical analysis included Wilcoxon signed rank test and Spearman correlation. Results: The median nucleated red blood cell counts/100 white blood cell counts for manual microscopy in umbilical cord blood; placental samples were 7.5 and 3.0, respectively (P <.0001). The median nucleated red blood cell counts for flow cytometric determination in umbilical cord blood and placental samples were 11.3 and 8.6, respectively (P <.0001). The Spearman correlation between manually counted umbilical cord blood samples and the placental tissue specimens was 0.66 (P <.0001). The Spearman correlation between flow cytometrically counted umbilical cord blood nucleated red blood cell and nucleated red blood cell counts that were obtained from the placenta was statistically significant (r = 0.74, P <.0001). The Spearman correlation between manual microscopy and flow cytometry for umbilical cord samples and their matched placental tissue specimens were 0.80 and 0.58, respectively, with all probability values at <.0001. Conclusion: Previous studies have reported an association between acute and chronic hypoxia and elevated nucleated red blood cells. Our results indicate that in vitro placental nucleated red blood cell counts correlate with umbilical cord nucleated red blood cell counts and suggest that antenatal evaluation of fetal nucleated red blood cells could be achieved by placental fine-needle aspiration biopsy. (Am J Obstet Gynecol 2003;189:155-8.)

Placental passage of antidepressant medications.

This study determined the placental transfer of antidepressants and their metabolites. A total of 38 pregnant women taking citalopram, fluoxetine, paroxetine, or sertraline participated. Maternal and umbilical cord blood samples were obtained to determine antidepressant and metabolite concentrations. Antidepressant and metabolite concentrations were detectable in 86.8% of umbilical cord samples. The mean ratios of umbilical cord to maternal serum concentrations ranged from 0.29 to 0.89. The lowest ratios were for sertraline and paroxetine; the highest were for citalopram and fluoxetine. Maternal doses of sertraline and fluoxetine correlated with umbilical cord concentrations of these medications. Umbilical cord concentrations of antidepressants and their metabolites were almost invariably lower than corresponding maternal concentrations. Maternal doses predicted umbilical concentrations of fluoxetine and sertraline. Mean umbilical cord to maternal serum ratios were significantly lower for sertraline than fluoxetine, suggesting that sertraline may produce less fetal medication exposure than fluoxetine near delivery.

Umbilical Cord Ghrelin Concentrations in Asian and Caucasian Neonates

Objectives: To compare the relationship between cord plasma ghrelin and growth hormone (GH) concentrations and birth weight in Asian and Caucasian neonates. Methods: We measured umbilical cord ghrelin and GH concentrations in 180 full-term newborns [4 groups of 45 according to ethnicity (Caucasian/Asian) and sex]. Results: Ghrelin was detectable in all umbilical cord samples (mean ± SD: 611 ± 267, range 193–2,010 pg/ml). There was no significant difference in ghrelin concentrations between Asian and Caucasian male or female neonates. In contrast, GH values were significantly affected by sex (p = 0.001) and ethnicity (p = 0.006). Except for a weak (r = –0.33, p < 0.03) negative correlation between ghrelin and GH in male Caucasian neonates, ghrelin and GH concentrations were independent. Conclusions: Umbilical cord concentrations of ghrelin, a potent orexigenic and GH stimulatory agent, are similar in Caucasian and Asian newborns, suggesting that ghrelin does not play a causal role in the differences in body composition and GH metabolism observed in these neonates.

Cardiac troponin I, cardiac troponin T and creatine kinase MB concentrations in umbilical cord blood of healthy term neonates.

To measure and compare cardiac troponin I, cardiac troponin T and creatine kinase MB concentrations in the umbilical cord blood of healthy term infants and to investigate the relationship between maternal and neonatal troponin values at birth. Troponin I, troponin T and creatine kinase MB concentrations were measured from the umbilical cord samples of 85 healthy term neonates and in the blood samples of their respective mothers at birth. Median (interquartile range) umbilical cord concentrations were 0 microg/L (0-0) for troponin I, 0 microg/L (0-0.019) for troponin T and 4.90 microg/L (3.90-6.61) for creatine kinase MB. Troponin I and T concentrations were higher than the detection limit for the assay in 2 (2.3%) and 41 (48.2%) neonates, respectively. Two mothers (2.3%) had cTnT levels above the detection limit; none of them had increased levels of cTnI. Probably owing to differences in expression and assay detection limits, cord blood troponin T concentrations are frequently over the detection limit at birth, while troponin I is mostly undetectable and comparable with that in healthy pregnant women. These cardiac regulatory proteins are of neonatal origin and are not influenced by maternal levels.