Umbilical Cord Plasma Concentrations Research Articles

Evaluation of Vitamin E Isoforms in Placental Tissue and Their Relationship with Maternal Dietary Intake and Plasma Concentrations in Mother-Infant Dyads.

α-tocopherol is a vitamin E isoform with potent antioxidant activity, while the γ-tocopherol isoform of vitamin E exerts more pro-inflammatory effects. In maternal-fetal environments, increased plasma α-tocopherol concentrations are associated with positive birth outcomes, while higher γ-tocopherol concentrations are linked with negative pregnancy outcomes. However, little is known about tocopherol concentrations in placental tissue and their role in modulating placental oxidative stress, a process that is implicated in many complications of pregnancy. The objectives of this research are to evaluate the concentrations of α- and γ-tocopherol in placental tissue and assess relationships with maternal and umbilical cord plasma concentrations. A total of 82 mother-infant dyads were enrolled at the time of delivery, and maternal and umbilical cord blood samples and placenta samples were collected. α- and γ-tocopherol concentrations in these samples were analyzed by high-performance liquid chromatography (HPLC). γ-tocopherol concentrations demonstrated significant, positive correlations among all sample types (p-values < 0.001). Placental tissue had a significantly lower ratio of α:γ-tocopherol concentrations when compared to maternal plasma and umbilical cord plasma (2.9 vs. 9.9 vs. 13.2, respectively; p < 0.001). Additional research should explore possible mechanisms for tocopherol storage and transfer in placental tissue and assess relationships between placental tocopherol concentrations and measures of maternal-fetal oxidative stress and clinical outcomes of pregnancy.

Transplacental methadone exposure and risk of Neonatal Opioid Withdrawal Syndrome.

Neonatal opioid withdrawal syndrome (NOWS) is a condition that often occurs in neonates born to mothers who received methadone treatment for opioid use disorder during pregnancy. Early identification and treatment of infants at risk of NOWS may improve clinical outcomes. The purpose of this study was to evaluate whether maternal and umbilical cord plasma concentrations of methadone and its metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), could predict the need for NOWS treatment. Single-center prospective study. University of Michigan Neonatal Intensive Care Unit. The study included 11 opioid-dependent mother-infant dyads, where the mothers were treated with methadone at 34 weeks' gestation or later. Maternal and cord blood samples were collected from the study participants. Maternal and cord plasma concentrations of methadone and EDDP were determined. Six out of the 11 infants required treatment for NOWS. Maternal methadone plasma concentrations were comparable between infants requiring and not requiring NOWS treatment (329.1 ± 229.7 ng/mL vs. 413.2 ± 329.8 ng/mL). However, the average cord plasma methadone concentration in infants who did not require NOWS treatment was 2.9-fold higher than in those who required the treatment (120.0 ± 88.6 ng/mL vs. 40.9 ± 24.4 ng/mL), although the difference was not statistically significant. The ratios of maternal-to-cord methadone plasma concentrations were significantly higher in patients who required treatment for NOWS compared with those who did not (7.7 ± 1.9 vs. 3.5 ± 1.6, p = 0.003). Maternal and cord plasma EDDP concentrations and the maternal-to-cord plasma EDDP concentration ratios did not differ between patients who required and did not require treatment for NOWS. The results suggest that methadone permeability across the blood-placental barrier may affect in utero exposure to methadone, and the maternal-to-cord methadone plasma concentration ratio could be a potential biomarker for predicting the need for NOWS treatment.

Maternal Diet Quality and the Health Status of Newborns.

The maternal diet during pregnancy affects neonatal health status. The objective of this study was to assess the nutritional quality of the maternal diet, and its contamination by persistent organic pollutants (POPs), in pregnant women living in two areas of the Czech Republic with different levels of air pollution, and subsequently to assess the relationship of these two factors with birth weight and neonatal oxidative stress. To determine the level of oxidative stress, 8-isoprostane concentrations in umbilical cord plasma were measured. The overall nutritional quality of the maternal diet was not optimal. Of the nutritional factors, protein intake proved to be the most significant showing a positive relationship with birth weight, and a negative relationship with the oxidative stress of newborns. Dietary contamination by persistent organic pollutants was low and showed no statistically significant relationship with birth weight. Only one of the 67 analyzed POPs, namely the insecticide dichlorodiphenyltrichloroethane (DDT), showed a statistically significant positive relationship with the level of neonatal oxidative stress.

Plasma Concentrations and Maternal-Umbilical Cord Plasma Ratios of the Six Most Prevalent Carotenoids across Five Groups of Birth Gestational Age.

Carotenoids are antioxidant nutrients with the potential to provide protection against oxidative stress. Plasma carotenoid concentrations are lower in newborn infants compared to their mothers; however, limited information is available regarding how concentrations differ by gestational age. The objective of this research is to assess maternal and umbilical cord plasma carotenoid concentrations and maternal-umbilical cord plasma ratios across five groups of birth gestational age. Mother-infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood. Plasma carotenoids were analyzed by HPLC and LC-MS/MS. Birth gestational age was categorized into five groups, and the Kruskal–Wallis test compared carotenoid concentrations and maternal-umbilical cord plasma ratios between these groups. A p-value of < 0.05 was considered statistically significant. 370 mother-infant dyads were included, with most infants delivered at early term (20.3%) or term (64.6%). Though maternal plasma concentrations increased with birth gestational age, we observed less variability in umbilical cord plasma concentrations, thus the maternal-umbilical cord plasma ratio also increased with birth CGA groups for lutein + zeaxanthin (p = 0.008), β-cryptoxanthin (p = 0.027), α-carotene (p = 0.030); β-carotene approached significance (p = 0.056). Additional research is needed to determine if carotenoid concentrations were physiologic to varying gestational ages or if they were impacted by factors associated with preterm birth.

Placenta is Capable of Protecting the Male Fetus from Exposure to Environmental Bisphenol A

Embryo–fetal exposure to bisphenol A (BPA) could be related to poor male reproductive parameters in rodents, but this concept has not been convincingly confirmed in humans. We investigated the association of environmental BPA exposure of pregnant women with selected endocrine and anthropometric parameters of male newborns. We analyzed plasma BPA from pregnant mothers, umbilical cord, and placental tissues (n = 117/each group) by liquid chromatography and mass spectrometry. LH, FSH, AMH, TGFβ2, inhibin B, and selected sex steroids were measured in cord plasma. The infant anthropometric parameters included anogenital distance, stretched penile length, head circumference, birthweight, and length. The median BPA concentrations in maternal and umbilical cord plasma, and in placental tissue were 19.0, 8.0, and 22.2 nmol/L, respectively, the levels thus being over twofold lower in the fetal circulation than in the mother or placenta. The BPA concentrations measured were 100–1000-fold lower than those demonstrated in animal experiments to have endocrine disrupting effects. Multivariable regression analysis indicated no significant correlations between the maternal/fetal/placental BPA concentrations and any of the hormone levels or anthropometric parameter measured. Plasma concentrations of BPA confirmed both maternal, placenta, and fetal exposure to environmental BPA, but the concentrations were orders of magnitude lower than those with documented endocrine disrupting activity. Moreover, the maternal/fetal concentration gradient as well as the lack of correlations of BPA levels with any major endocrine or anthropometric parameters measured in the newborns suggest a protective role for the placenta in reducing fetal exposure to the environmental BPA.

Fetal Release of Copeptin in Response to Maternal Oxytocin Administration: A Randomized Controlled Trial.

To test whether an oxytocin challenge test raises neonatal levels of copeptin, the C-terminal portion of proarginine vasopressin, a sensitive stress marker elevated in neonates born by vaginal delivery as opposed to elective cesarean delivery. In a randomized controlled trial in women with a singleton pregnancy undergoing elective cesarean delivery at greater than 36 weeks of gestation and no contractions or rupture of membranes, we compared arterial umbilical cord plasma concentrations of copeptin between neonates exposed to an oxytocin challenge test before elective cesarean delivery and those administered saline infusion (placebo group). Women randomized to an oxytocin challenge test received 5 international units/500 mL oxytocin Ringer lactate infused at a rate of 12 mL/h and doubled every 10 minutes until it induced three uterine contractions per 10-minute interval, at which point it was discontinued. Neonatal copeptin levels were the primary endpoint. Secondary endpoints included biochemical and physiologic parameters of fetal and maternal well-being. From January 2012 to October 2012 and from September 2013 to January 2015, 78 women underwent an oxytocin challenge test and 78 placebo infusion, of whom 12 and 11, respectively, were excluded as a result of insufficient blood sample volume for analysis. Umbilical cord plasma copeptin levels [median (range)] were higher in neonates who underwent an oxytocin challenge test than those who underwent placebo infusion: 22.2 (3.22-2,319) compared with 7.39 (2.5-344.6) pmol/L (P<.001). There were no statistically significant differences between the two groups in secondary outcomes. Oxytocin challenge test-induced contractions before elective cesarean delivery trigger fetal copeptin release. ClinicalTrials.gov, https://clinicaltrials.gov, NCT01962701.

Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial

Preeclampsia complicates approximately 3-5% of pregnancies and remains a major cause of maternal and neonatal morbidity and mortality. It shares pathogenic similarities with adult cardiovascular disease as well as many risk factors. Pravastatin, a hydrophilic, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, has been shown in preclinical studies to reverse various pathophysiological pathways associated with preeclampsia, providing biological plausibility for its use for preeclampsia prevention. However, human trials are lacking. As an initial step in evaluating the utility of pravastatin in preventing preeclampsia and after consultation with the US Food and Drug Administration, we undertook a pilot randomized controlled trial with the objective to determine pravastatin safety and pharmacokinetic parameters when used in pregnant women at high risk of preeclampsia. We conducted a pilot, multicenter, double-blind, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12(0/7) and 16(6/7) weeks' gestation were assigned to daily pravastatin 10 mg or placebo orally until delivery. Primary outcomes were maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included rates of preeclampsia and preterm delivery, gestational age at delivery, birthweight, and maternal and cord blood lipid profile (clinicaltrials.gov identifier NCT01717586). Ten women assigned to pravastatin and 10 to placebo completed the trial. There were no differences between the 2 groups in rates of study drug side effects, congenital anomalies, or other adverse or serious adverse events. There was no maternal, fetal, or neonatal death. Pravastatin renal clearance was significantly higher in pregnancy compared with postpartum. Four subjects in the placebo group developed preeclampsia compared with none in the pravastatin group. Although pravastatin reduced maternal cholesterol concentrations, umbilical cord cholesterol concentrations and infant birthweight were not different between the groups. The majority of umbilical cord and maternal pravastatin plasma concentrations at the time of delivery were below the lower limit of quantification of the assay. Pravastatin use was associated with a more favorable pregnancy angiogenic profile. This study provides preliminary safety and pharmacokinetic data regarding the use of pravastatin for preventing preeclampsia in high-risk pregnant women. Although the data are preliminary, no identifiable safety risks were associated with pravastatin use in this cohort. This favorable risk-benefit analysis justifies using pravastatin in a larger clinical trial with dose escalation.

Clinical chorioamnionitis at term V: umbilical cord plasma cytokine profile in the context of a systemic maternal inflammatory response.

Microbial invasion of the fetus due to intra-amniotic infection can lead to a systemic inflammatory response characterized by elevated concentrations of cytokines in the umbilical cord plasma/serum. Clinical chorioamnionitis represents the maternal syndrome often associated with intra-amniotic infection, although other causes of this syndrome have been recently described. The objective of this study was to characterize the umbilical cord plasma cytokine profile in neonates born to mothers with clinical chorioamnionitis at term, according to the presence or absence of bacteria and/or intra-amniotic inflammation. A cross-sectional study was conducted, including patients with clinical chorioamnionitis at term (n=38; cases) and those with spontaneous term labor without clinical chorioamnionitis (n=77; controls). Women with clinical chorioamnionitis were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) and amniotic fluid interleukin (IL)-6 concentration into three groups: 1) no intra-amniotic inflammation; 2) intra-amniotic inflammation without detectable microorganisms; or 3) microbial-associated intra-amniotic inflammation. A fetal inflammatory response syndrome (FIRS) was defined as an umbilical cord plasma IL-6 concentration >11 pg/mL. The umbilical cord plasma concentrations of 29 cytokines were determined with sensitive and specific V-PLEX immunoassays. Nonparametric statistical methods were used for analysis, adjusting for a false discovery rate of 5%. 1) Neonates born to mothers with clinical chorioamnionitis at term (considered in toto) had significantly higher median umbilical cord plasma concentrations of IL-6, IL-12p70, IL-16, IL-13, IL-4, IL-10 and IL-8, but significantly lower interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF)-α concentrations than neonates born to mothers with spontaneous term labor without clinical chorioamnionitis; 2) neonates born to mothers with clinical chorioamnionitis at term but without intra-amniotic inflammation had higher concentrations of IL-6, IL-12p70, IL-13, IL-4, IL-5, and IL-8, but lower IFN-γ, than neonates not exposed to clinical chorioamnionitis, suggesting that maternal fever in the absence of intra-amniotic inflammation leads to a change in the fetal cytokine network; 3) there were significant, positive correlations between maternal and umbilical cord plasma IL-6 and IL-8 concentrations (IL-6: Spearman correlation=0.53; P<0.001; IL-8: Spearman correlation=0.42; P<0.001), consistent with placental transfer of cytokines; 4) an elevated fetal plasma IL-6 (>11 pg/mL), the diagnostic criterion for FIRS, was present in 21% of cases (8/38), and all these neonates were born to mothers with proven intra-amniotic infection; and 5) FIRS was associated with a high concentration of umbilical cord plasma IL-8, IL-10 and monocyte chemoattractant protein (MCP)-1. Neonates born to mothers with clinical chorioamnionitis at term had higher concentrations of umbilical cord plasma cytokines than those born to mothers without clinical chorioamnionitis. Even neonates exposed to clinical chorioamnionitis but not to intra-amniotic inflammation had elevated concentrations of multiple cytokines, suggesting that intrapartum fever alters the fetal immune response.

Umbilical cord plasma and salivary insulin and leptin concentrations in AGA neonates: a preliminary report

Background and objective: Insulin and leptin hormones are important regulators of food intake and energy balance. There is limited information about insulin and leptin hormones in neonates. This preliminary study aimed to investigate the concentrations of insulin and leptin in umbilical cord plasma and neonate’s saliva and their relationships.Methods: Umbilical cord plasma and salivary samples were obtained from 13 healthy, appropriate for gestational age (AGA) neonates. Insulin and leptin concentrations in umbilical cord plasma and saliva were measured using the MILLIPLEX MAP® Human Metabolic Hormone Magnetic Bead Panel.Results: Insulin concentrations in umbilical cord plasma correlates positively and significantly with leptin concentrations in umbilical cord plasma (r = 0.55, p = 0.04).Conclusions: More research is needed to explore the relationships between insulin and leptin hormones in neonate’s saliva.

Tacrolimus placental transfer at delivery and neonatal exposure through breast milk

The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml(-1)) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml(-1)). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml(-1)) and unbound drug concentrations (0.003 ± 0.001 ng ml(-1)) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant.

Soluble ST2 in the fetal inflammatory response syndrome: in vivo evidence of activation of the anti-inflammatory limb of the immune response

Objective: Inflammation is a mechanism of host response to infection, which can be harmful when inappropriately modulated. Soluble ST2 (sST2) is a decoy receptor of interleukin (IL)-33, and this complex modulates the balance in the Th1/Th2 immune response. Moreover, sST2 inhibits the production of pro-inflammatory cytokines in cooperation with an anti-inflammatory cytokine, IL-10. The objectives of this study were to: (1) determine whether umbilical cord plasma sST2 concentration differs between preterm neonates with and without funisitis and between those with and without the fetal inflammatory response syndrome (FIRS); and (2) evaluate the relationship between sST2 and IL-10 among neonates with funisitis and/or FIRS.Methods: Umbilical cord plasma was collected from neonates delivered prematurely due to preterm labor or preterm prelabor rupture of membranes with (n = 36), and without funisitis (n = 30). FIRS (umbilical cord IL-6 concentration ≥17.5 pg/mL) was identified in 29 neonates. Plasma sST2 and IL-10 concentrations were determined by enzyme linked immune sorbent assay.Results: The median umbilical cord plasma sST2 concentration was 6.7-fold higher in neonates with FIRS than in those without FIRS (median 44.6 ng/mL, interquartile range (IQR) 13.8–80.3 ng/mL versus median 6.7 ng/mL, IQR 5.6–20.1 ng/mL; p < 0.0001). Similarly, the median umbilical cord plasma sST2 concentration was 2.7-fold higher in neonates with funisitis than in those without funisitis (median 19.1 ng/mL; IQR 7.1–75.0 ng/mL versus median 7.2 ng/mL; IQR 5.9–23.1 ng/mL; p = 0.008). There was a strong positive correlation between sST2 and IL-10 in neonates with funisitis and/or FIRS (Spearman’s Rho = 0.7, p < 0.0001).Conclusion: FIRS and funisitis are associated with an elevation of umbilical cord plasma concentrations of soluble ST2. This protein represents an important mediator of the immune response in neonates diagnosed with FIRS by promoting an anti-inflammatory effect in association with IL-10.

Trace elements’ concentrations in maternal and umbilical cord plasma at term gestation: a comparison between active labor and elective cesarean delivery

Objective. Trace elements are minerals required in minute quantities to maintain proper physical functioning. The role of trace elements in the process of parturition is poorly understood. This study was aimed to determine levels of trace elements’ concentration in maternal plasma and umbilical venous and arterial plasma at term during active labor vs elective cesarean delivery (CD).Study design. A prospective case–control study was conducted. Forty healthy parturients in active labor at term with their newborns were compared to 40 healthy parturients matched for maternal age, parity, and gestational age, who delivered by elective CD (before commencement of labor). Samples of maternal venous blood and umbilical cord arterial and venous blood were drawn immediately following delivery. Trace elements’ concentrations were measured using the inductively coupled plasma mass spectrometer (ICP-MS).Results. Significant higher levels of manganese (Mn) and selenium were found in maternal venous plasma during active labor vs elective CD. Magnesium (Mg) levels were significantly higher in maternal venous blood during elective CD compared to active labor. Umbilical cord artery levels of Mg, Mn, and zinc (Zn) were significantly higher in active term labor vs elective CD. Also, significant higher levels of copper and Zn were found in umbilical cord vein between active labor and elective CD.Conclusion. Trace elements’ concentrations differ significantly in fetal blood during active labor vs elective CD. Hence, trace elements may play a crucial role in the process of human parturition.

Umbilical cord plasma 25‐hydroxyvitamin D concentration and immune function at birth: the Urban Environment and Childhood Asthma study

Recent studies have reported conflicting data on the association between maternal intake of vitamin D during pregnancy and asthma. To assess the influence of prenatal vitamin D status on immune function at birth. In an inner-city birth cohort of 568 newborns, 520 of whom had at least one atopic parent, we measured the umbilical cord (UC) plasma concentration of 25-hydroxyvitamin D (25(OH)D) and the cytokine responses of UC blood mononuclear cells (UCMCs) to stimuli including phytohaemagglutinin (PHA), lipopolysaccharide (LPS), and peptidoglycan. In a subset, the UCMC expression of regulatory T cell markers and the suppressive activity of CD4(+) CD25(+) UCMCs were measured. Results The 25th, 50th, and 75th percentiles of UC plasma 25(OH)D level were 15.0, 20.2, and 25.6 ng/mL, respectively. Most cytokine responses of UCMC were not correlated with UC 25(OH)D concentration; however, IFN-γ release after LPS stimulation was weakly positively correlated with UC 25(OH)D concentration (r=0.11, P=0.01). PHA responses were not significantly correlated with 25(OH)D concentration. The UC plasma 25(OH)D concentration was inversely related to the number of CD25(+) (r=-0.20, P=0.06), CD25(Bright) (r=-0.21, P=0.05), and CD25(+) FoxP3 (r=-0.29, P=0.06) cells as a proportion of CD4(+) T cells in UC blood (r=-0.26, P=0.04) but not to the suppressive activity of CD4(+) CD25(+) cells (r=0.17, P=0.22). UC 25(OH)D concentration was not correlated with most UCMC cytokine responses to multiple stimuli. There was a suggestion of a weakly positive correlation with IFN-γ release after LPS stimulation. The proportions of CD25(+) , CD25(Bright) , and CD25(+) FoxP3 cells to total CD4(+) T cells were inversely correlated with UC 25(OH)D concentration. Our findings suggest that higher vitamin D levels at birth may be associated with a lower number of T-regulatory cells. Vitamin D status in utero may influence immune regulation in early life.

P572 Interleukin-6 concentrations in maternal and umbilical cord plasma and the early onset neonatal infection

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S575-S575 Poster presentations P572 Interleukin-6 concentrations in maternal and umbilical cord plasma and the early onset neonatal infection J. Zegarska, J. ZegarskaSearch for more papers by this authorB. Wolski, B. WolskiSearch for more papers by this authorR. Adamczak, R. AdamczakSearch for more papers by this authorW. Szymanski, W. SzymanskiSearch for more papers by this authorW. Dobrzynski, W. DobrzynskiSearch for more papers by this authorM. Gruszka, M. GruszkaSearch for more papers by this author J. Zegarska, J. ZegarskaSearch for more papers by this authorB. Wolski, B. WolskiSearch for more papers by this authorR. Adamczak, R. AdamczakSearch for more papers by this authorW. Szymanski, W. SzymanskiSearch for more papers by this authorW. Dobrzynski, W. DobrzynskiSearch for more papers by this authorM. Gruszka, M. GruszkaSearch for more papers by this author First published: 20 November 2009 https://doi.org/10.1016/S0020-7292(09)62062-2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S575-S575 RelatedInformation

Effects of prenatal exposure to organochlorines on thyroid hormone status in newborns from two remote coastal regions in Québec, Canada

Background Several prospective studies have revealed that prenatal exposure to polychlorinated biphenyls (PCBs) and other organochlorine compounds (OCs) affect neurodevelopment during infancy. One of the mechanisms by which PCBs might interfere with neurodevelopment is a deficit in thyroid hormone (TH) concentrations. Objectives We investigated the potential impact of transplacental exposure to PCBs and hexachlorobenzene (HCB) on TH concentrations in neonates from two remote coastal populations exposed to OCs through the consumption of seafood products. Methods Blood samples were collected at birth from the umbilical cord of neonates from Nunavik ( n=410) and the Lower North Shore of the St. Lawrence River ( n=260) (Québec, Canada) for thyroid parameters [thyroid-stimulating hormone (TSH), free T 4 (fT 4), total T 3 (tT 3), and thyroxine-binding globuline (TBG)] and contaminants analyses. Results In multivariate models, umbilical cord plasma concentrations of PCB 153, the predominant PCB congener, were not associated with TH and TSH levels in both populations. Prenatal exposure to HCB was positively associated with fT 4 levels at birth in both populations (Nunavik, β=0.12, p=0.04; St. Lawrence, β=0.19, p<0.01), whereas TBG concentrations were negatively associated with PCB 153 concentrations ( β=−0.13, p=0.05) in the St. Lawrence cohort. Conclusion OCs levels were not associated to a reduction in THs in neonates from our two populations. Essential nutrients derived from seafood such as iodine may have prevented the negative effects of OCs on the thyroid economy during fetal development.

Umbilical cord plasma homocysteine concentrations at delivery in pregnancies complicated by pre‐eclampsia

To determine whether homocysteine concentrations in umbilical cord plasma of neonates born to mothers with pre-eclampsia are elevated compared to concentrations in neonates born to normotensive women. Maternal blood from eight women with pre-eclampsia and ten women without pre-eclampsia was collected on admission for labour. Cord blood was collected from these same pregnancies at delivery. Plasma was extracted and stored at -70 degrees C. Samples were batch-analysed for homocysteine. Maternal plasma homocysteine levels were observed to be significantly higher in the pregnancies complicated by pre-eclampsia compared to the control pregnancies (P = 0.043) with median levels of 5.4 micromol/L (interquartile range (IQR) 4.6-7.9; range 3.6-16.7) versus 4.1 micromol/L (IQR 3.4-5.1, range 3.1-6.7). Homocysteine concentrations in umbilical cord plasma in pregnancies complicated by pre-eclampsia were also significantly higher compared to those in normotensive pregnancies (P = 0.016) with median concentration levels of 5.3 micromol/L (IQR 4.8-7.2, range 2.5-16.6) versus 3.8 micromol/L (IQR 2.8-4.4, range 0.8-1.6). Both maternal and umbilical cord plasma homocysteine concentrations were elevated in pregnancies complicated by pre-eclampsia compared to normotensive controls.

Validation of a sensitive LC–MS assay for quantification of glyburide and its metabolite 4-transhydroxy glyburide in plasma and urine: An OPRU Network study

Glyburide (glibenclamide, INN), a second generation sulfonylurea is widely used in the treatment of gestational diabetes mellitus (GDM). None of the previously reported analytical methods provide adequate sensitivity for the expected sub-nanogram/mL maternal and umbilical cord plasma concentrations of glyburide during pregnancy. We developed and validated a sensitive and low sample volume liquid chromatographic–mass spectrometric (LC–MS) method for simultaneous determination of glyburide (GLY) and its metabolite, 4-transhydroxy glyburide (M1) in human plasma (0.5 mL) or urine (0.1 mL). The limits of quantitation (LOQ) for GLY and M1 in plasma were 0.25 and 0.40 ng/mL, respectively whereas it was 1.06 ng/mL for M1 in urine. As measured by quality control samples, precision (% coefficient of variation) of the assay was <15% whereas the accuracy (% deviation from expected) ranged from −10.1 to 14.3%. We found that the GLY metabolite, M1 is excreted in the urine as the glucuronide-conjugate.

The intensity of the fetal inflammatory response in intraamniotic inflammation with and without microbial invasion of the amniotic cavity

Intraamniotic inflammation is a risk factor for adverse pregnancy and neonatal outcome, regardless of the presence or absence of a positive amniotic fluid (AF) culture. The purpose of this study was to determine whether the intensity of a fetal inflammatory response (FIR) differs between cases of intraamniotic inflammation with microbiologically proven infection and cases with negative AF cultures. The FIR was examined in 89 cases of women with preterm premature rupture of membranes who delivered singleton preterm newborn infants within 48 hours of amniocentesis. AF was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas. AF white blood cell (WBC) count and matrix metalloproteinase-8 (MMP-8) determinations were performed to assess the presence of intraamniotic inflammation. Intraamniotic inflammation was defined as an elevated AF MMP-8 concentration (>23 ng/mL). The intensity of the FIR was determined by the umbilical cord plasma concentrations of C-reactive protein (CRP). Patients were divided into 3 groups according to the presence or absence of intraamniotic inflammation and AF culture results: group 1, without intraamniotic inflammation and with a negative AF culture (n = 28); group 2, with intraamniotic inflammation and with a negative AF culture (n = 26); group 3, with a positive AF culture (n = 35). Neonates who were born to mothers with intraamniotic inflammation and negative AF cultures had a significantly higher median umbilical cord plasma CRP concentration than did those without intraamniotic inflammation and a negative AF culture (P < .005) but a significantly lower median cord plasma CRP concentration than did those with proven AF infection (P < .05). Patients with intraamniotic inflammation and a negative AF culture had significantly higher median AF MMP-8 concentrations and WBC count than did those without intraamniotic inflammation and a negative AF culture (P < .001). However, there was no significant difference in the median AF MMP-8 and WBC count between patients with intraamniotic inflammation and a negative AF culture and those with proven AF infection (MMP-8, P > .1, and WBC, P = .09). Intraamniotic inflammation without documented AF infection is a risk factor for a systemic FIR. However, the magnitude of the FIR in those cases was lower than in those with documented AF infection.

Phthalate monoesters in perfusate from a dual placenta perfusion system, the placenta tissue and umbilical cord blood

Fetal exposure to phthalates may be associated with adverse reproductive effects, including cryptorchidism and decreased semen quality. Information about human placental transfer is needed to qualify the hypotheses. A dual recirculating placenta perfusion system to monitor concentrations of eight phthalate monoesters in fetal and maternal perfusates was established. In addition to perfusate background measures of phthalate monoesters, the concentrations in umbilical cord plasma and placenta tissue were measured. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), monobutyl phthalate (mBP), and mono (2-ethyl-hexyl) phthalate (mEHP) were detected in both maternal and fetal perfusate, demonstrating a release of compounds from tissue or blood to perfusates. The distribution of compounds between perfusate, umbilical cord plasma, and tissue was in accordance with the physical–chemical properties of the compounds. Results from the present study of compounds residing in the tissue are essential before studying human transplacental transfer, storage, and metabolism of selected phthalate monoesters.

Umbilical cord plasma concentrations of free morphine following single-dose diamorphine analgesia and their relationship to dose-delivery time interval, Apgar scores and neonatal respiration

Objective To find the effect of dose-delivery interval on cord-blood levels of diamorphine metabolites and its effect on Apgar sores and neonatal respiration. Study design Pilot study conducted in labour ward of a district general hospital. One hundred women who had normal delivery and received single dose of 7.5 mg of intramuscular injection of diamorphine in labour were recruited in the study. A 2.0 ml sample of umbilical venous blood was collected from the placenta after delivery of the baby. The sample was analysed using RIA method to measure free morphine. Details about the labour and baby's condition at birth were recorded. Results The concentration of free morphine in the umbilical venous blood was significantly associated with the dose-delivery interval (coefficient (95% CI) = 1.08(0.99–1.18), p < 0.001). Twenty neonates had low Apgar score (≤7) at 1 min. The odds of such a low score were raised with higher log free morphine in the cord venous plasma, but not statistically significantly (OR (95% CI) = 5.3 (0.84–34), p = 0.08). Fourteen neonates required resuscitation. The odds of requiring resuscitation were significantly raised with higher log free morphine: OR (95% CI) = 9.3 (1.0–86), p = 0.05. Conclusion Concentration of free morphine in the umbilical venous blood after delivery was significantly associated with the dose-delivery interval and this had significant effect on the need for resuscitation.