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Lipoprotein(a) Levels at Birth and in Early Childhood: The COMPARE Study.
Strandkjær, N, Hansen, MK, Nielsen, ST, Frikke-Schmidt, R, Tybjærg-Hansen, A, Nordestgaard, BG, Tabor, A, Bundgaard, H, Iversen, K, Kamstrup, PR
The Journal of clinical endocrinology and metabolism. 2022;(2):324-335
Abstract
BACKGROUND AND OBJECTIVE High lipoprotein(a) is a genetically determined causal risk factor for cardiovascular disease, and 20% of the adult population has high levels (ie, >42 mg/dL, >88 nmol/L). We investigated whether early life lipoprotein(a) levels measured in cord blood may serve as a proxy for neonatal venous blood levels, whether lipoprotein(a) birth levels (ie, cord or venous) predict levels later in life, and whether early life and parental levels correlate. METHODS The Compare study is a prospective cohort study of newborns (N = 450) from Copenhagen, Denmark, including blood sampling of parents. Plasma lipoprotein(a) was measured in cord blood (N = 402), neonatal venous blood (N = 356), and at 2 (N = 320) and 15 months follow-up (N = 148) of infants, and in parents (N = 705). RESULTS Mean lipoprotein(a) levels were 2.2 (95% CI, 1.9-2.5), 2.4 (2.0-2.7), 4.1 (3.4-4.9), and 14.6 (11.4-17.9) mg/dL in cord, neonatal venous, and 2- and 15-month venous samples, respectively. Lipoprotein(a) levels in cord blood correlated strongly with neonatal venous blood levels (R2 = 0.95, P < 0.001) and neonatal levels correlated moderately with 2- and 15-month levels (R2 = 0.68 and 0.67, both P < 0.001). Birth levels ≥ 90th percentile predicted lipoprotein(a) > 42 mg/dL at 15 months with positive predictive values of 89% and 85% for neonatal venous and cord blood. Neonatal and infant levels correlated weakly with parental levels, most pronounced at 15 months (R2 = 0.22, P < 0.001). CONCLUSIONS Lipoprotein(a) levels are low in early life, cord blood may serve as a proxy for neonatal venous blood, and birth levels ≥ 90th percentile can identify newborns at risk of developing high levels.
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Metabolomics comparison of cord and peripheral blood-derived serum eye drops for the treatment of dry eye disease.
Quartieri, E, Marraccini, C, Merolle, L, Pulcini, S, Buzzi, M, Guardi, M, Schiroli, D, Baricchi, R, Pertinhez, TA
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2021;(4):103155
Abstract
Allogeneic peripheral blood-derived (PBS) serum eye drops have been largely used in the treatment of dry eye disease (DED). Recently, cord blood has emerged as an effective alternative serum source (cord blood serum, CBS), containing a higher amount of growth factors than PBS, it holds the promise of a better capability to stimulate corneal healing. However, the lack of a standardized method for preparation, dispensation, storage and a poor biochemical characterization still hamper the establishment of a clinical consensus. Here the metabolomes of the two different serum eye drop preparations were compared using proton nuclear magnetic resonance spectroscopy. We found that both PBS and CBS contained several organic compounds, the majority of them already detected in human tears and may be thereby considered lacrimal substitutes. Metabolites having in the multivariate statistical analysis Partial least squares discriminant analysis (PLS-DA) a VIP scores > 1.0 were considered to be significantly different. All the metabolites identified were found to have a p < 0.05 in the univariate analysis. CBS, in particular, showed the highest amount of choline, myo-inositol, glutamine, creatine and β-hydroxybutyrate. These evidences constitute relevant advances towards serum eye drops characterization and confirm that cord blood is a valid alternative source of serum eye drops.
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Gestational diabetes mellitus decreased umbilical cord blood polyunsaturated fatty acids: a meta-analysis of observational studies.
Hai-Tao, Y, Zhi-Heng, G, Yi-Ru, C, Yue-Ting, L, Hai-Ying, Z, Ya-Juan, L, Lin, X
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102318
Abstract
BACKGROUND Polyunsaturated fatty acid (PUFA) is important for the development of the fetal brain, and the retina. Gestational diabetes mellitus (GDM) may influence maternal and fetal fatty acid metabolism, in turn affecting fetal growth and development. In several studies, maternal and fetal PUFA metabolic differences have been reported between mothers with and without GDM, but not in other studies. Thus, the aim of this meta-analysis (registration number: CRD42020220448) was to compare levels of linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), and total n-3 and n-6 PUFA between mothers with and without GMD and their fetuses. METHODS We performed a meta-analysis of observational studies on maternal and fetal fatty acid metabolism, published until May 2021. In addition, we performed subgroup analysis depending on the analyzed tissues (plasma/serum, erythrocyte membrane, or placenta) and the expression modes of fatty acids (concentration or percentage). RESULTS We included 24 observational studies involving 4335 maternal datasets and 12 studies involving 1675 fetal datasets in the meta-analysis. Levels of AA, DHA, and n-6 and n-3 PUFA were lower in the cord blood of mothers with GDM than in controls (P < 0.05). Compared to that in controls, in erythrocyte membranes, the percentages of AA, DHA, and n-6 and n-3 PUFA in total fatty acid were lower in mothers with GDM (P < 0.05), but in plasma/serum, the percentages of AA, DHA, and n-6 PUFA in total fatty acid were higher in mothers with GDM (P < 0.05). CONCLUSIONS GDM appears to influence the transfer of PUFAs from mothers to fetuses. The percentage of PUFAs in maternal plasma/serum was higher, and that in erythrocyte membranes was lower in mothers with GDM compared to those with normal glucose tolerance.
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Vitamin D status in women with dichorionic twin pregnancies and their neonates: a pilot study in China.
Li, X, Yu, J, Wen, L, Li, Q, Yan, J, Tian, J, Tong, C, Tong, Q, Qi, H, Saffery, R, et al
BMC pregnancy and childbirth. 2021;(1):279
Abstract
BACKGROUND Vitamin D deficiency is a global public health issue in women and children and is associated with adverse impacts on child growth, such as rickets. However, prior studies have mainly focused on measuring vitamin D levels in singleton pregnant women and their offspring, and very limited studies have revealed the prevalence of vitamin D deficiency in twin pregnant women and their offspring. The aim of this study was to investigate vitamin D levels in twin-pregnant women and their neonates. We also explored the correlation of maternal vitamin D levels with neonatal outcomes and infant growth. METHODS A prospective subcohort investigation was carried out among 72 dichorionic, diamniotic twin-pregnant mothers and their twin offspring from the Longitudinal Twin Study. Peripheral blood was collected from the mothers in the third trimester, and cord blood was collected from neonates at birth to identify 25[OH]D levels. Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected. RESULTS The average maternal 25[OH]D level was 31.78 ng/mL, with 19.4% being deficient and 20.8% insufficient, while the average neonatal 25[OH]D level was 15.37 ng/mL, with 99.3% being deficiency or insufficient. A positive correlation was found between maternal and neonatal 25[OH]D levels (beta-value: 0.43, 95% CI: 0.37, 0.49). Interestingly, the higher the maternal 25[OH]D level was, the smaller the cotwin birthweight discordance (beta-value: -2.67, 95% CI: - 5.11, - 0.23). In addition, the infants of mothers with vitamin D deficiency were more likely to be allergic to foods at 6 months than those of mothers with vitamin D sufficiency. CONCLUSIONS Twin neonates were at high risk of vitamin D deficiency, although their mothers' vitamin D deficiency partially improved. Higher maternal vitamin D levels were associated with smaller discordance of cotwin birthweight. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR-OOC-16008203 , 1st April 2016.
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Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial.
Taesuwan, S, McDougall, MQ, Malysheva, OV, Bender, E, Nevins, JEH, Devapatla, S, Vidavalur, R, Caudill, MA, Klatt, KC
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2021;(12):e22063
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Abstract
Pregnancy places a unique stress upon choline metabolism, requiring adaptations to support both maternal and fetal requirements. The impact of pregnancy and prenatal choline supplementation on choline and its metabolome in free-living, healthy adults is relatively uncharacterized. This study investigated the effect of prenatal choline supplementation on maternal and fetal biomarkers of choline metabolism among free-living pregnant persons consuming self-selected diets. Participants were randomized to supplemental choline (as choline chloride) intakes of 550 mg/d (500 mg/d d0-choline + 50 mg/d methyl-d9-choline; intervention) or 25 mg/d d9-choline (control) from gestational week (GW) 12-16 until Delivery. Fasting blood and 24-h urine samples were obtained at study Visit 1 (GW 12-16), Visit 2 (GW 20-24), and Visit 3 (GW 28-32). At Delivery, maternal and cord blood and placental tissue samples were collected. Participants randomized to 550 (vs. 25) mg supplemental choline/d achieved higher (p < .05) plasma concentrations of free choline, betaine, dimethylglycine, phosphatidylcholine (PC), and sphingomyelin at one or more study timepoint. Betaine was most responsive to prenatal choline supplementation with increases (p ≤ .001) in maternal plasma observed at Visit 2-Delivery (relative to Visit 1 and control), as well as in the placenta and cord plasma. Notably, greater plasma enrichments of d3-PC and LDL-C were observed in the intervention (vs. control) group, indicating enhanced PC synthesis through the de novo phosphatidylethanolamine N-methyltransferase pathway and lipid export. Overall, these data show that prenatal choline supplementation profoundly alters the choline metabolome, supporting pregnancy-related metabolic adaptations and revealing biomarkers for use in nutritional assessment and monitoring during pregnancy.
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Cord blood metabolic markers are strong mediators of the effect of maternal adiposity on fetal growth in pregnancies across the glucose tolerance spectrum: the PANDORA study.
Lee, IL, Barr, ELM, Longmore, D, Barzi, F, Brown, ADH, Connors, C, Boyle, JA, Kirkwood, M, Hampton, V, Lynch, M, et al
Diabetologia. 2020;(3):497-507
Abstract
AIMS/HYPOTHESIS We aimed to assess associations between cord blood metabolic markers and fetal overgrowth, and whether cord markers mediated the impact of maternal adiposity on neonatal anthropometric outcomes among children born to Indigenous and Non-Indigenous Australian women with normal glucose tolerance (NGT), gestational diabetes mellitus (GDM) and pregestational type 2 diabetes mellitus. METHODS From the Pregnancy and Neonatal Outcomes in Remote Australia (PANDORA) study, an observational cohort of 1135 mother-baby pairs, venous cord blood was available for 645 singleton babies (49% Indigenous Australian) of women with NGT (n = 129), GDM (n = 419) and type 2 diabetes (n = 97). Cord glucose, triacylglycerol, HDL-cholesterol, C-reactive protein (CRP) and C-peptide were measured. Multivariable logistic and linear regression were used to assess the associations between cord blood metabolic markers and the outcomes of birthweight z score, sum of skinfold thickness (SSF), being large for gestational age (LGA) and percentage of body fat. Pathway analysis assessed whether cord markers mediated the associations between maternal and neonatal adiposity. RESULTS Elevated cord C-peptide was significantly associated with increasing birthweight z score (β 0.57 [95% CI 0.42, 0.71]), SSF (β 0.83 [95% CI 0.41, 1.25]), percentage of body fat (β 1.20 [95% CI 0.69, 1.71]) and risk for LGA [OR 3.14 [95% CI 2.11, 4.68]), after adjusting for age, ethnicity and diabetes type. Cord triacylglycerol was negatively associated with birthweight z score for Indigenous Australian women only. No associations between cord glucose, HDL-cholesterol and CRP >0.3 mg/l (2.9 nmol/l) with neonatal outcomes were observed. C-peptide mediated 18% (95% CI 13, 36) of the association of maternal BMI with LGA and 11% (95% CI 8, 17) of the association with per cent neonatal fat. CONCLUSIONS/INTERPRETATION Cord blood C-peptide is an important mediator of the association between maternal and infant adiposity, across the spectrum of maternal glucose tolerance.
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Pregnancy or cord 25-hydroxyvitamin D is not associated with measures of body fat or adiposity in children from three months to three years of age. An Odense Child Cohort study.
Larsen, SD, Christensen, ME, Dalgård, C, Lykkedegn, S, Andersen, LB, Andersen, MS, Glintborg, D, Christesen, HT
Clinical nutrition (Edinburgh, Scotland). 2020;(6):1832-1839
Abstract
BACKGROUND & AIMS The susceptibility to overweight in adults born during winter season may suggest foetal programming of prenatal vitamin D levels on adiposity. We investigated whether cord or pregnancy serum 25-hydroxyvitamin D (s-25OHD) was associated with infant and child body fat measures in a Danish population-based prospective cohort. METHODS In the Odense Child Cohort, 1905 singletons had cord s-25OHD and data on waist circumference (WC), weight, body mass index (BMI), and sum of skin folds (SSF) at median 3.7 months, 18.9 months and three years' age. Early and late pregnancy samples of s-25OHD (mean gestational age 12 and 29 weeks) were chosen as secondary exposures. Multiple linear and logistic regression as well as linear mixed models was applied testing the relation between cord and pregnancy s-25OHD and body fat outcomes and their Z-scores by use of updated national reference populations. Models were adjusted for maternal educational level, maternal ethnicity, pre-gestational BMI and season of birth, a priori stratified by sex. RESULTS The median [IQR] cord s-25OHD was 45.5 [31.1; 60.9] nmol/L. Cord s-25OHD <50 nmol/L was found in 57.5%; values < 25 nmol/L in 16.3%. The mean Z-scores of body fat measures at all ages were in the range of -0.32 to +0.42. No consistent associations were found between s-25OHD in cord, early pregnancy or late pregnancy and WC, weight, BMI, SSF, or their Z-scores at ages 3.7 months, 18.9 months, or 3 years. Neither did a computed composite outcome (WC, SSF, BMI, or weight >90th vs. ≤90 percentile) associate with cord or pregnancy s-25OHD. CONCLUSION Cord or pregnancy s-25OHD was not associated with measures of body fat or adiposity in children up to three years of age. Our data suggested no programming effect of maternal s-25OHD on offspring obesity in a relatively lean and healthy population of mothers.
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Cord blood zinc status effects on pregnancy outcomes and its relation with maternal serum zinc levels: a systematic review and meta-analysis.
Akdas, S, Yazihan, N
World journal of pediatrics : WJP. 2020;(4):366-376
Abstract
BACKGROUND The association between maternal and cord blood zinc level and pregnancy outcomes remains uncertain. The present study aims to assess whether maternal blood zinc level represents cord blood zinc level correctly. METHODS In this meta-analysis, systematic search was performed in PubMed, Web of Science, and Scopus databases for relevant available English articles which included mean and standard deviation values of cord blood zinc level up to April 2019. For the assessment of the relation between cord blood zinc level and pregnancy outcomes, the pooled standard mean difference with 95% confidence interval (CI) was used and 23 studies were analyzed. RESULTS Cumulative analysis showed that cord blood zinc level was found significantly decreased in pregnancies with complications compared with healthy pregnancy controls [REM: P = 0.0007, mean difference - 7.9 (- 12.48, - 3.31)]. For further analysis, maternal serum zinc level status was determined from same studies to compare with cord blood levels and subgroups were detected as "Preterm", "Preeclampsia", "Small for gestational age/Intrauterine growth restriction and Low birth weight". It was observed that cord blood zinc levels in subgroup analysis were also decreased and/or tend to be decreased compared to healthy pregnancies, except for preeclampsia subgroup. Also, a correlation was seen between cord blood and maternal blood zinc level status (R = 0.4365, 95% CI - 0.530, 0.756; P = 0.0351). CONCLUSION It was thought that cord blood zinc level might tend to decrease more than maternal serum zinc level in the pathological conditions during pregnancies.
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Maternal arterial blood gas values during delivery: Effect of mode of delivery, maternal characteristics, obstetric interventions and correlation to fetal umbilical cord blood.
Zaigham, M, Helfer, S, Kristensen, KH, Isberg, PE, Wiberg, N
Acta obstetricia et gynecologica Scandinavica. 2020;(12):1674-1681
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INTRODUCTION Obstetricians routinely use biochemical parameters from non-pregnant women to assess the condition of the laboring mother. However, it is well known that pregnancy leads to significant physiological changes in most organ systems. The aim of this study was to determine normal values for maternal arterial blood gases during vaginal deliveries as compared with control values from planned cesarean sections. We also wanted to elucidate the effect of various maternal characteristics, mode of delivery and obstetric interventions on blood gas values. MATERIAL AND METHODS We carried out a randomly selected, prospective-observational cohort study of 250 women undergoing vaginal delivery and 58 women undergoing planned cesarean section at the Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden. RESULTS We found significant differences for gestational age, parity, umbilical venous blood pH, pCO2 and lactate values between the two study groups (P < .005). Significantly lower pH, pCO2 , pO2 and sO2 were found in mothers delivering vaginally. Higher base deficit, hemoglobin, bilirubin, potassium, glucose and lactate were found in vaginal deliveries than in planned cesarean sections (P < .02). Maternal body mass index (BMI), smoking and hypertension were not significantly correlated to acid base parameters in women with vaginal deliveries. On the other hand, multiple regression showed significant associations for the use of epidural anesthesia on maternal pH (P < .05) and pO2 (P < .01); and synthetic oxytocin on pCO2 (P = .08), glucose (P < .00) and lactate (P < .02) levels in maternal arterial blood. Maternal arterial pH, pCO2 and lactate values correlated significantly to values in venous umbilical cord blood (P < .000). CONCLUSIONS Maternal arterial blood gas parameters varied significantly according to mode of delivery, the use of epidural anesthesia and synthetic oxytocin.
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Association between maternal or cord blood concentrations of 25-hydroxycholecalciferol or vitamin D supplementation during pregnancy and the cytokines profile in the umbilical cord blood: Systematic literature review.
de O Farias, MC, Cavalcante, TLT, Assunção, ML, Bueno, NB
The Journal of steroid biochemistry and molecular biology. 2020;:105739
Abstract
INTRODUCTION Evidence suggests that vitamin D suppresses the production of pro-inflammatory cytokines and induces the production of anti-inflammatory cytokines during pregnancy. OBJECTIVES To assess, through a systematic literature review, the relationship between maternal or cord blood concentrations of 25-hydroxycholecalciferol (25-OH-D) or vitamin D supplementation during pregnancy and the cytokines profile in the umbilical cord. METHODS The following databases were searched: PUBMED, CENTRAL, Web of Science, LILACS, and gray literature, up to July 2020. The search strategy included terms related to the exposure (25-OH-D) and the primary outcome (cytokines). Observational studies and randomized clinical trials were included, measuring cytokines in the umbilical cord blood, or in ex vivo bioassays, and blood concentrations of 25-OH-D, either throughout pregnancy or in the umbilical cord blood. Studies with twin pregnancies, with placental or autoimmune diseases, were excluded. The protocol is registered in PROSPERO (number CRD42019136643). RESULTS From 14,605 unique articles identified in the databases, 28 were read in full, and of these, eight met the eligibility criteria, being three randomized clinical trials, and five observational studies. The eight studies showed adequate methodological quality. IL-10 was the most studied cytokine, being reported in seven studies. There were higher concentrations of IL-10 in the umbilical cord of women with 25-OH-D sufficiency in the observational studies. Clinical trials showed mixed results with the use of ex vivo bioassays with several stimulants. Associations with other cytokines were less consistent or absent. CONCLUSION 25-OH-D status is positively associated with the IL-10 levels of the umbilical cord, in observational studies.