Ratio Of Cord Blood Research Articles

Abstract P207: Regulation of Fetal-Placental ACE and ACE2 in COVID-19 Exposed Pregnancies Compared to Hypertensive and Healthy Pregnancies

Introduction: Higher risks of preterm birth and fetal growth restriction are observed in COVID-19 pregnancies. The infection mechanism, linked to a potential depletion of the cardioprotective protein ACE2, which serves as a receptor for SARS-CoV-2, could pose additional risks for mothers and fetuses. An ACE2/ACE imbalance, favoring ACE, has been seen in hypertensive (HT) pregnancies and is linked to poor outcomes, including pre-eclampsia. This study aims to assess whether similar changes in ACE and ACE2 regulation in placentas and umbilical cord blood occur in COVID-19 compared to HT and healthy (Ctrl) pregnancies, and whether this imbalance is associated with impaired vascular structure. Methods: A retrospective cohort study recruited 77 pregnancies (25 COVID-19, 16 HT, 36 Ctrl) at Montreal Hospital Sacré-Coeur. Placental infarction was assessed in histological sections, umbilical cord fibrosis by Masson's trichrome staining, and placental ACE2 content by immunohistochemistry. ACE and ACE2 activity were measured by fluorometric assay in umbilical cord plasma. Data are presented as mean 95% CI. Linear regression was used for correlations, Kruskal-Wallis and Mann-Whitney tests for group comparisons. Results: Maternal age, gestational age, and the proportion of male/female fetuses were similar between groups. Ctrl group had lower rates of C-section delivery, obesity, and gestational diabetes compared to COVID-19 and HT pregnancies. Although ACE2 content in placentas was reduced in HT pregnancies, the COVID-19 group had significantly higher content compared to HT and Ctrl pregnancies (23.4 CI=20.4-26.4 vs. 15.5 CI=9.7-21.3 and 17.6 CI=15.1-20.1, respectively, p<0.01). The ACE2/ACE activity ratio in cord blood was significantly reduced in COVID-19 and HT groups compared to Ctrl (3.1 CI=2.4-3.6, 2.5 CI=1.7-3.1, and 4.1 CI=3.5-4.8, p<0.01), indicating an imbalance favoring ACE activity in HT and COVID-19 groups. The ACE2/ACE ratio negatively correlated with umbilical cord fibrosis (slope=-3.1 CI= -6.1 to -0.1, p=0.04) and was significantly lower in placentas with tissue infarction (2.5 CI=1.2-3.8 vs. 4.6 CI=3.8-5.3, p<0.01). Conclusion: HT pregnancies have reduced ACE2 content and an ACE2/ACE activity imbalance in cord blood. COVID-19 pregnancies show a similar imbalance in cord blood but significantly higher ACE2 content in the placenta. This imbalance is associated with structural changes in fetal-placental vessels, suggesting a link to poor pregnancy outcomes.

Association of Zn and Cu Levels in Cord Blood and Maternal Milk with Pregnancy Outcomes among the Slovenian Population.

Trace elements, including zinc (Zn) and copper (Cu), are known to play important roles in human health. The present study aimed to assess the levels of Zn and Cu in cord blood and maternal milk and to analyze their association with maternal and infant characteristics and pregnancy outcomes in a Slovenian study population of mothers and their neonates recruited within the PHIME prospective cohort study. The study included 324 mothers, but the data on Zn and Cu levels in both cord blood and maternal milk was available for 243 mothers. Questionnaires were used to assess the socio-demographic and health status of the mothers, their lifestyle habits (including detailed nutritional habits), and their residential and occupational histories. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to measure Zn and Cu levels in cord blood and maternal milk. Low Zn levels in cord blood were associated with lower gestational age and birth weight and were correlated with an increased probability of the birth of small for gestational age (SGA) infants. Maternal smoking influenced the Cu levels in both cord blood and maternal milk. Cord blood Cu levels were higher and Cu levels in maternal milk were lower in smoking compared to non-smoking mothers. Most importantly, a decreased Zn/Cu ratio in cord blood was associated with lower gestational age and lower birth weight. This indicates the overall positive effects of Zn and negative effects of Cu on pregnancy outcomes.

Systematic review of the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnant and lactating individuals and their infants.

BackgroundThere is significant risk of complications and vulnerability to severe COVID‐19 disease in pregnancy, yet hesitancy exists around COVID‐19 vaccination during pregnancy and lactation.ObjectiveTo summarize the safety, immunogenicity, and effectiveness of COVID‐19 vaccines in pregnancy and lactation.Search strategyA systematic search of MEDLINE, Embase, PubMed, medRxiv, and bioRxiv.Selection criteriaIdentified original studies published on pregnant and/or lactating individuals who received one or more doses of a COVID‐19 vaccine.Data collection and analysisA descriptive summary organized by safety, immunogenicity, and effectiveness outcomes of COVID‐19 vaccination in pregnancy and lactation.Main resultsIn total, 23 studies were identified. Humoral response and functional immunity were interrogated and found. Increasing placental transfer ratios in cord blood were associated with increasing time from the first vaccine dose to delivery. Safety data indicated that pregnant and lactating populations experienced vaccine‐related reactions at similar rates to the general population. No increased risk of adverse obstetrical or neonatal outcomes were reported. One study demonstrated that pregnant individuals were less likely to experience COVID‐19 when vaccinated.ConclusionCOVID‐19 vaccination in pregnant and lactating individuals is immunogenic, does not cause significant vaccine‐related adverse events or obstetrical and neonatal outcomes, and is effective in preventing COVID‐19 disease.

Ambient air pollution exposure during pregnancy and cardio-metabolic markers in cord blood: The Healthy Start study

BACKGROUND AND AIM: Prenatal air pollution exposure has been associated with adverse cardiometabolic outcomes in childhood. It is unknown whether evidence of metabolic disruption associated with air pollution may be identified at birth. We estimated associations between maternal residential exposure to air pollution during pregnancy and metabolic and lipid biomarkers in cord blood collected at delivery. METHODS: This study included 812 mother-infant pairs enrolled in the prospective, Colorado-based Healthy Start study (2009-2014). Using inverse-distance-weighted interpolation of data obtained from stationary monitors, we estimated daily particulate matter ≤2.5 micrometers (PM2.5) and ozone (O3) concentrations at participant residences. Daily estimates were averaged by trimester, full pregnancy, and the 7- and 30- days prior to delivery. Outcomes were cord blood concentrations of glucose, insulin, leptin, total and high-density lipoprotein cholesterol, free fatty acids, and triglycerides. Glucose-insulin ratio was calculated as an indirect measure of insulin sensitivity. We used multiple linear regression to estimate associations between PM2.5 and O3 and cord blood metabolic and lipid biomarkers. Covariates included maternal, infant, and meteorological characteristics. RESULTS:Higher O3 exposure, during both recent and longer-term exposure periods during pregnancy, was consistently associated with higher insulin and lower glucose-insulin ratio in cord blood. For example, an interquartile range increase in full pregnancy O3 (6.3 ppb) was associated with a 0.12 log-µIU/ml (95% confidence interval: 0.03, 0.21) increase in cord blood insulin, after adjusting for covariates. There was limited evidence supporting positive associations between PM2.5 and leptin and O3 and total cholesterol. There were inverse associations between PM2.5 and triglycerides, during certain periods of pregnancy. CONCLUSIONS:Prenatal air pollution exposure was associated with cardiometabolic biomarkers in cord blood, most notably for O3 and insulin. Future studies should examine whether these changes persist into childhood and their implications on offspring health. KEYWORDS: prenatal exposure, air pollution, lipids, metabolism, neonate

Maternal Exposure to Perfluorooctane Sulfonate (PFOS) Is Associated with Maternal Hyperglycaemia and Adverse Neonatal and Childhood Outcomes

Perfluorooctane sulfonate (PFOS) belongs to a class of endocrine-disrupting chemicals, perfluoroalkyl chemicals (PFCs), implicated in adiposity. Although supposedly phased out since 2002, its use remains widespread in Asia. We aim to examine the relationship between exposure to PFOS and maternal hyperglycaemia and metabolic outcomes in the offspring. We measured blood PFOS and other PFCs in archived samples taken at 24-32weeks gestation from mothers in the Hong Kong centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study between 2002-2004. All mothers underwent 75g OGTT and GDM was diagnosed according to the IADPSG/WHO 2013 criteria. Pregnancy outcomes, neonatal anthropometrics and childhood outcomes at 7 years were documented. PFCs were measured using high performance LC-MS-MS. We completed analysis of PFCs in 1,601 maternal samples, a subset of 99 cord blood samples, and 970 offspring at 7 years follow-up. There is strong correlation among PFOS and other PFCs in cord blood (ρ=0.51-0.74, p<0.001), as well as correlation with maternal levels (ρ=0.60, p<0.001). Ratio of cord blood to maternal PFOS was 0.60. Using regression analysis with adjustment for maternal age, BMI, and offspring gender, maternal PFOS showed association with maternal 1 hour glucose, 2 hour glucose, HbA1c, AUC during OGTT and GDM, though only the association with HbA1c remained significant using log-transformed PFOS (beta 0.0746 ± 0.0132, p=1.7x10-8). Log-transformed maternal PFOS was associated with higher birthweight, lower birth length, higher ponderal index and lower neonatal sum of skin fold thickness (beta -0.337 ± 0.085, p=7.1x 10-5), after adjustment for all covariates. Maternal PFOS during pregnancy was associated with lower height in offspring at age 7, but not offspring glycaemic parameters. Exposure to PFOS may be an important contributing factor to the epidemic of hyperglycaemia in pregnancy and childhood metabolic disorders in Asia. Disclosure R.C.W. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd.. C.H.T. Tam: None. G. Cheung: None. W. Lowe: None. B.E. Metzger: None. W.H. Tam: None. C.K. Wong: None.

The maternal-fetal gradient of free and esterified phytosterols at the time of delivery in humans

High dietary intakes of phytosterols (Phyto), such as those consumed by vegans and vegetarians, are not recommended for cholesterol-lowering in pregnant women (PW) because the safety of their use during pregnancy has not been fully established [1]. Information on Phyto in pregnancy is very limited. To characterize the maternal-fetal gradient of free and esterified Phyto at the time of delivery in humans. PW who had a term delivery at the Obstetrics and Gynecology Unit of the University Hospital of Padua (Padua, Italy), between November 2016 and March 2017, participated in the study. Fatty acids (FA), cholesterol (Chol), Chol metabolites (7-dehydrocholesterol, 7-DHChol; lathosterol, Latho; 7α-hydroxycholesterol, 7α-OHChol), and Phyto (campesterol, Camp; stigmasterol, Stigma; sitosterol, Sito) were measured in both maternal (MB) and cord blood (CB) at the time of delivery. Non-pregnant adult volunteers (Ref-NA) served as a reference. Thirty-four term PW and 12 Ref-NA signed informed consent and were studied. Plasma total Phyto concentrations in CB were up to 20-fold lower than in MB (p<0.05). Positive and significant correlations were found between total Phyto of MB-CB pairs (p<0.01), and between total FA and Camp of MB (p<0.05). Interestingly, free Chol to Chol ester ratio of CB did not differ from that of MB, and free Phyto to Phyto ester ratios were higher in CB than in MB (p<0.001). No differences were found between Phyto concentrations of MB and Ref-NA. However, free Chol to Chol ester ratio, and free Phyto to Phyto ester ratios were higher in MB than in Ref-NA (p<0.05). Chol synthesis, as indicated by 7-DHChol to 7α-OHChol, Latho to 7α-OHChol, and Latho to Sito ratios, was greatest in CB and lowest in Ref-NA. Our data suggest that free Phyto cross the human placenta more easily than Phyto ester. An elevated Stigma to Chol ratio in CB than in MB was also described for the first time. The impact of these findings on the neonatal outcomes remains to be elucidated.

Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32–36 weeks, n = 51). Term placentas were used as controls (T, 37–41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p <0.05). In addition, gestational age was positively correlated with mRNA expression (Rho = 0.7), and negatively with protein concentration (Rho = -0.7 for chorionic and -0.43 for basal plate). PCFT/HCP1 mRNA was lower in PT placentas, without changes in protein levels. RFC did not differ in PT placentas compared to controls. PT newborns presented higher cord blood folate level (p = 0.049) along with lower vitamin B12 concentration compared to controls (p = 0.037).In conclusion, placental FOLR1 mRNA was positively associated with gestational age. Conversely, FOLR1 protein concentrations along with folate/vitamin B12 ratio in cord blood were negatively associated with gestational age. Placental FOLR1 is likely the main placental folate transporter to the fetus in newborns.

The perinatal androgen to estrogen ratio and autistic-like traits in the general population: a longitudinal pregnancy cohort study.

BackgroundPrenatal androgen exposure has been hypothesized to be linked to autism spectrum disorder (ASD). While previous studies have found a link between testosterone levels in amniotic fluid and autistic-like traits, a similar relationship has not been found for testosterone in umbilical cord blood. However, it may be the net biological activity of multiple androgens and estrogens that influences postnatal effects of prenatal sex steroids. Accordingly, composite levels of androgens (A) and estrogens (E) were investigated, along with their ratio, in relation to autistic-like traits in young adulthood.MethodsSex steroid data in umbilical cord blood were available from 860 individuals at delivery. Samples were analyzed for androgens (testosterone, androstenedione, and dehydroepiandrosterone) and estrogens (estrone, estradiol, estriol, and estetrol). Levels of bioavailable testosterone, estradiol, and estrone were measured and used to calculate A and E composites and the A to E ratio. Participants were approached in early adulthood to complete the autism-spectrum quotient (AQ) as a self-report measure of autistic-like traits, with 183 males (M = 20.10 years, SD = 0.65 years) and 189 females (M =19.92 years, SD = 0.68 years) providing data.ResultsMales exhibited significantly higher androgen composites and A to E composite ratios than females. Males also scored significantly higher on the details/patterns subscale of the AQ. Subsequent categorical and continuous analyses, which accounted for covariates, revealed no substantial relationships between the A/E composites or the A to E ratio and the AQ total or subscale scores.ConclusionsThe current study found no link between the A/E composites or the A to E ratio in cord blood and autistic-like traits in the population as measured by the AQ. These outcomes do not exclude the possibility that these sex steroid variables may predict other neurodevelopmental traits in early development.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-015-9114-9) contains supplementary material, which is available to authorized users.

Cord blood n-3 LC-PUFA is associated with adiponectin concentrations at 10 years of age

An elevated ratio of n-6 to n-3 long-chain (LC-) polyunsaturated fatty acids (PUFA) may be a potential risk factor for obesity development. N-3 LC-PUFA are thought to alter adiponectin concentrations, and thus may have a beneficial effect on weight development. We analysed the association between n-3 LC-PUFA concentrations in cord blood and adiponectin concentrations at 10 years.Fatty acid composition was measured in cord blood and at 10 years of age by gas chromatography, and adiponectin concentrations were measured only at 10 years of age in 237 children from the Munich LISAplus birth cohort study. Linear regression models assessed associations between n-3 LC-PUFA, n-6 LC-PUFA and the n-6/n-3 ratio in cord blood with adiponectin concentrations at 10 years of age. LC-PUFA were presented as percentages and categorized into tertiles. Regression models were adjusted for LC-PUFA percentages at 10 years of age and other potential confounding factors.Cord blood n-3 LC-PUFA tertiles were significantly associated with adiponectin concentrations in an inverse J-shaped relationship [2nd tertile versus 1st tertile: Beta=1.84 (SE=0.65), and 3rd tertile versus 1st tertile: 1.02 (0.68), p-value<0.01 (ANOVA)]. Further, cord blood n-6/n-3 ratios were significantly associated with adiponectin concentrations [2nd tertile versus 1st tertile: 0.14 (0.67), and 3rd tertile versus 1st tertile: −1.37 (0.68), p-value=0.03 (ANOVA)]. The cord blood n-6 LC-PUFA tertiles were not associated with adiponectin concentrations.Our results suggest that a higher n-3 LC-PUFA concentrations and a lower n-6/n-3 ratio in cord blood are associated with higher adiponectin concentrations at 10 years of age.

Interaction between cadmium (Cd), selenium (Se) and oxidative stress biomarkers in healthy mothers and its impact on birth anthropometric measures.

To our knowledge, this study may be the first to examine the antagonistic role of selenium (Se) on oxidative stress induced by cadmium (Cd) and its impact on birth measures. Cd and Se levels were measured in umbilical-cord blood and the placentas of a subsample of 250 healthy mothers who participated between 2005 and 2006 in the project "Prenatal Exposure to Pollutants". The median Cd levels in cord and maternal blood and placental tissue were 0.78μg/l, 0.976μg/l and 0.037μg/g dry wt., respectively. The median levels of Se in cord serum and placental tissue were 65.68μg/l and 1.052μg/g dry wt., respectively. Se was more than 100-fold in molar excess over Cd in both cord serum and placental tissue. The median molar Cd/Se ratios in cord serum and placental tissue were 0.008 and 0.024, respectively, which were much lower than unity. This study suggests that both Cd and Se play a role in the mechanism of oxidative stress, but, the process underlying this mechanism remains unclear. Nevertheless, three biomarkers of oxidative stress had inconsistent relationships with Cd and/or Se in various matrices, perhaps due to potential untested confounders. Our results generally support an association between low in utero exposure to Cd and the anthropometric development of the fetus. Adjusted regression models indicated a negative association of cord blood Cd levels ≥0.78μg/l with Apgar 5-min scores and birth height. Maternal Cd levels ≥0.976μg/l were associated with a 5.94-fold increased risk of small-for-gestational-age births, which increased to 7.48-fold after excluding preterm births. Placenta weight decreased with increasing placental Cd levels ≥0.037μg/g dry wt. (p=0.045), an association that became stronger after excluding preterm births or adjusting for birth weight. Cord Se levels ≥65.68μg/l were positively associated with placenta weight (p=0.041) and thickness (p=0.031), an association that remained unchanged after excluding preterm births. Cord Se levels, however, were negatively associated with cephalization index, but only after excluding preterm births (p=0.017). Each birth measure was again modeled as a function of the Cd/Se ratios in cord blood and placenta tissue. Interestingly cord ratios ≥0.008 were negatively associated with Apgar-5min score (p=0.047), birth weight (p=0.034) and placenta thickness (p=0.022). After excluding preterm births, only the association with placenta thickness remained significant (p=0.021), while birth weight (p=0.053) was marginally significant. In contrast, cephalization index increased with Cd/Se ratios ≥0.008 (p=0.033), an association that became marginally significant after excluding preterm births (p=0.058). For placental Cd/Se ratios ≥0.024, only placenta weight was reduced with (p=0.037) and without (p=0.009) the inclusion of preterm births. These findings do not support an antagonistic mechanism between Cd and Se. The role of oxidative mechanisms either induced by Cd exposure or alleviated by Se on these birth anthropometric measures was examined by principal component analysis. Se did not have a clear protective role against Cd-induced adverse effects despite its substantial excess over Cd, and its role in alleviating oxidative stress by reducing malondialdehyde levels. The results may suggest that the extent of the Se beneficial effects is not governed only by its concentration but also by the chemical forms of Se that interact with various proteins. Consequently, the speciation of Se in such studies is essential for understanding and predicting Se availability for absorption.

Imbalance between Th1 and Th2 cells in cord blood is influenced by maternal allergic rhinitis and associated with atopic dermatitis during the first two years of life

To investigate the influence of maternal atopy on cord blood effector T cells and to identify these biologic markers as predictors of atopic dermatitis (AD). Seventy mother-infant pairs were recruited in this prospective birth cohort study. Suspected factors for allergy, including maternal allergic history, total serum IgE, and maternal age at birth, were collected. Mother peripheral blood samples and cord blood were obtained and assayed for the percentage of interferon-γ (IFN-γ) and interleukin 4 (IL-4) producing T cells(Th1 and Th2 respectively) using flow cytometry. Their offspring at the age of 2 years old were evaluated by their dermatologist whether they had AD. Statistical analysis was performed using multiple logistic regression models and receiver-operating characteristic curve was employed to predict atopic dermatitis. Twenty-one allergic and 49 nonallergic mothers were recruited in this study. During the first two years of life, 15.7% children (n = 11) developed a physician-diagnosed AD (all children were the only child in the family). In group with maternal allergic rhinitis, a significantly increased percentage of Th2 was observed in peripheral blood of mother (7.10[1.18;16.1]% vs. 0.37[0.25;0.72]%, U = 10.0, P < 0.05) and cord blood of newborns (1.02[0.57;1.34]% vs. 0.21[0.15;0.42]%, U = 127.5, P < 0.05), respectively. Maternal atopic history did not affect the percentage of Th1 cells in cord blood (0.69[0.40;1.12]% vs.0.50[0.31;0.66]%, U = 361.0, P > 0.05). Children with reduced Th1/Th2 ratio in cord blood had a higher risk to develop AD (OR = 1.72, P = 0.001) . The model including Th1/Th2, maternal allergy, maternal age at birth and maternal total IgE showed high ability to discriminate children with and without AD. AUC was 0.907 (95% CI: 0.804-1.011, P < 0.001). Elevated IL-4⁺CD4⁺ T cells in cord blood were of relevance with maternal allergic history. Imbalance between Th1 cell and Th2 cell at birth are associated with maternal allergy and promoted subsequent AD development.

Cord blood LC‐PUFA composition and allergic diseases during the first 10 yr. Results from the LISAplus study

BackgroundIt has been suggested that n-6 and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) in blood are associated with risk of allergic diseases, although results are inconclusive. Low levels of n-6 LC-PUFA and high levels of n-3 LC-PUFA are anticipated to have beneficial effects. Pregnancy is considered a critical time period for imprinting the developing immune system. We examined whether n-6 LC-PUFA, n-3 LC-PUFA concentrations or the n-6/n-3 ratio in cord blood (CB) serum are associated with allergic diseases up to the age of 10 yr.MethodsThis analysis included 436 children from the Munich LISAplus birth cohort study. Information on doctor-diagnosed asthma, hay fever/allergic rhinitis, and eczema was collected using questionnaires completed at the ages 6 and 10 yr, and for eczema additionally at 2 yr. Specific immunoglobulin E (IgE) against inhalant allergens was measured at 6 and 10 yr. Fatty acid composition was measured by gas chromatography in serum from CB and from blood collected at 2, 6, and 10 yr. Associations between n-3, n-6 LC-PUFA concentrations, and the n-6/n-3 ratio in CB serum and allergic diseases or atopy were assessed using generalized estimating equations (GEE) considering the longitudinal structure. Models were adjusted for LC-PUFA concentrations at follow-up and potential confounding factors.ResultsThere was no significant association between n-3 LC-PUFA, n-6 LC-PUFA, or the n-6/n-3 ratio in CB serum with eczema, asthma, hay fever/allergic rhinitis, or aeroallergen sensitization.ConclusionsThere is no indication of a beneficial effect of increased n-3 LC-PUFA in CB serum on the development of any of the disease entities.

Age-dependent effects of cord blood long-chain PUFA composition on BMI during the first 10 years of life

In the present study, we investigated whether n-6 and n-3 long-chain PUFA (LC-PUFA) concentrations in cord blood (CB) serum are associated with BMI up to 10 years of age, after accounting for LC-PUFA composition at 2, 6 and 10 years. The study was based on 388 participants of the German LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood Plus the Influence of Traffic Emissions and Genetics) birth cohort study carried out in Munich. BMI was measured at 2, 6 and 10 years of age. Serum phospholipid fatty acid concentrations were measured by GC in CB and in blood collected at 2, 6 and 10 years of age. The association between n-3 LC-PUFA and n-6 LC-PUFA concentrations and n-6:n-3 LC-PUFA ratio in CB serum glycerophospholipids and BMI z-scores was assessed using linear mixed models adjusted for LC-PUFA composition at follow-up and potential confounders. Interaction terms between time of follow-up and LC-PUFA concentrations in CB were included. There was no consistent association between n-6 and n-3 LC-PUFA concentrations in CB and BMI over time. However, there was a significant interaction between n-6:n-3 LC-PUFA ratio in CB and time of follow-up with respect to BMI (P=0·0415): a negative effect at 2 years; no effect at 6 years; a positive effect at 10 years. BMI up to 10 years of age may be influenced by the n-6:n-3 ratio in CB serum glycerophospholipids in a time-varying fashion. The present results thereby highlight the importance of considering age when examining associations between fatty acid concentrations and BMI.

T cell subsets in cord blood are influenced by maternal allergy and associated with atopic dermatitis

This study aimed to investigate the influence of maternal allergy on cord blood regulatory and effector T cells and to evaluate their role as a predictor of atopic dermatitis (AD) during the first 2yr of life. Seventy mother-infant pairs were recruited in this prospective birth cohort study (21 allergic and 49 non-allergic mothers). Cord blood samples were collected and assayed for the percentage of regulatory T cells (Treg), interferon-γ (IFN-γ), and interleukin-4 (IL-4) producing T cells (Th1 and Th2, respectively) using flow cytometry. Experiments were undertaken to assess the function of cord blood CD4(+) CD25(+) CD127(-) Treg cells by cell proliferation and cytokine responses. Their offspring at the age of 2yr old were evaluated by dermatologists to determine whether they had AD. During the first 2yr of life, 15.7% of the children developed a physician-diagnosed AD. A significantly increased percentage of Th2 cell was observed in cord blood of newborns with maternal allergy. Treg/Th2 ratio significantly decreased among the offspring of allergic mothers. Treg cell-associated suppression of Th2 response was attenuated in Der p1-stimulated CD4(+) CD25(-) T cells from the offspring of allergic mothers. Children with reduced Th1/Th2 (p=0.001, OR=0.37) and Treg/Th2 (p=0.001, OR=0.47) ratio in cord blood had a higher risk of developing AD. Maternal allergic status is associated with increased percentage of IL-4(+) CD4(+) T cells and a reduced Treg/Th2 ratio in cord blood at their children's birth, which may predispose to an increased risk for developing AD.

Acylated/unacylated ghrelin ratio in cord blood: correlation with anthropometric and metabolic parameters and pediatric lifespan comparison

Ghrelin is a peptide with multiple functions that circulates in acylated (AG) and unacylated (UAG) forms. However, the role of ghrelin in neonates (NN) remains to be clarified. The aim of this study was to determine ghrelin concentrations of the two forms in NN to clarify their biological roles. As such, ghrelin levels at birth were compared with those in later life. Tertiary Care Center. In this cross-sectional study, we evaluated AG, UAG, AG/UAG ratio, and insulin levels in venous cord blood from NN and in fasted normal weight (NW) and obese (OB) children, both prepubertal and pubertal. We studied 82 NN, 82 NW, and 58 OB children. AG levels were lower in NN than in NW and OB children (P<0.0001), more specifically the prepubertal NW and OB children (P<0.0001). UAG levels were higher in NN than in NW and OB children (P<0.0001). Therefore, the AG/UAG ratio was lower in NN than in NW and OB children (P<0.0001). NN showed insulin levels similar to NW and lower than OB children (P<0.0001). At birth UAG was positively correlated with AG (Pearson: 0.425; P<0.0001) and negatively with insulin (-0.253; P<0.02). In NW and OB, UAG and AG were positively correlated to each other and negatively correlated with insulin and body mass index (-0.566; P<0.0001). NN compared with children, showed higher UAG and lower AG levels. The AG/UAG ratio showed a very different profile in NN, being lower than in NW and OB children, thus suggesting a different metabolic function for the two forms in NN. Further studies are needed to clarify the exact role of the different ghrelin forms in NN.

Determinants of birth weight in boys and girls

AbstractBoys are heavier at birth than girls, but girls have higher fat mass at birth than boys. Insulin action may play an important role of this different distribution. Animal models have shown that female offspring are more sensitive to maternal feeding and glucose values during pregnancy and weaning than male offspring. Newborn girls have higher insulin and proinsulin concentrations and total proinsulin‐to‐insulin ratios in cord blood than boys, despite lighter birth weight. In a cohort of 522 newborn above 37 gestational weeks we split between the sexes and studied associations between birth weights, parental anthropometrics and fasting maternal plasma glucose and insulin levels. Boys weighed 184g more than girls, they were 1.1 cm longer and head circumference differed by 0.86 (all p values &lt;0.01). Multiple linear regressions showed that parity, maternal body mass index, gestational age and maternal birth weight were associated with birth weight for both sexes, whereas maternal weight gain in pregnancy and maternal fasting plasma glucose at week 30‐32 were significantly associated with birth weight for girls only. The effect of fasting plasma glucose on birth weight in girls was twice as high as in boys (B=162, 95% CI 33.4‐291, p=0.01). Paternal birth weight was significantly associated with birth weight of boys, but no such association was seen for girls. This supports the notion that there is a genetic regulation along the male line. Girls may be more sensitive to intrauterine environment and maternal glucose values, as these have a stronger influence on birth weight of girls.

CD1c + immature myeloid dendritic cells are predominant in cord blood of healthy neonates

It has been suggested lately that some types of antigen presenting cells-myeloid dendritic (DC-1) cells can differentiate the immune response towards Th1 type immunity, whereas lymphoid cells (DC-2) can stimulate Th2 type immunity. It has been observed that neonates are deficient in Th1 response. The purpose of our study was to estimate the proportions of immature myeloid (CD1c +) and lymphoid (BDCA-2 +, BDCA-4 +) dendritic cells and the CD1c +:BDCA-2 + cell ratio in cord blood of healthy neonates in comparison with dendritic cells of healthy adults. Thirty healthy neonates born from normal pregnancies and 30 healthy adults were included in the study. The dendritic cells were isolated from cord and peripheral blood, stained with anti-CD1c, anti-BDCA-2, anti-BDCA-4, anti-CD123 and anti-CD19 monoclonal antibodies and estimated using flow cytometry. The percentage of CD1c + dendritic cells in cord blood of healthy newborns did not differ significantly when compared to those in peripheral blood of healthy adults. The percentages of cord blood BDCA-2 + and BDCA-4 + dendritic cells of neonates were significantly lower when compared to lymphoid dendritic cells in peripheral blood of adults. The CD1c +:BDCA-2 + ratio was significantly higher in cord blood of neonates in comparison with CD1c +:BDCA-2 + ratio in adult’s blood. Myeloid and lymphoid dendritic cells may be involved in the immune regulation during fetal development. Immature myeloid dendritic cells are predominant in cord blood of healthy neonates. Immature lymphoid dendritic cells are not the major population of dendritic cells in cord blood.

Cholesterol metabolism in normal and heterozygous familial hypercholesterolemic newborns

In heterozygous familial hypercholesterolemia (FH), serum low-density lipoprotein (LDL) cholesterol levels are frequently increased in utero. A unique Finnish FH population, FH-North Karelia (FH-NK), has been identified, providing an excellent opportunity to study the diagnostic significance of cholesterol metabolism in FH. For that purpose, we investigated lipoprotein lipids, cholesterol precursors (squalene, methyl, and demethyl sterols), cholestanol, and plant sterols in FH-NK newborns (n = 5), non-FH siblings (n = 7), and controls (n = 20) at birth and after 1-year follow-up in 8 FH-NK and 5 non-FH children. The sum of concentrations (micrograms per deciliter) of methyl sterol (8-monomethylsterol, methostenol, 8-dimethylsterol, 8,24-dimethylsterol, and lanosterol) and squalene was higher in FH newborns than in non-FH siblings but overlapped with one control case. Cord-blood total or LDL cholesterol values could not be used for diagnostic purposes, whereas 1-year LDL cholesterol values were highly superior to those measured at birth. The methyl sterol ratio in cord blood was 29 to 193 102 mmol/mol cholesterol and was undetectable in serum at the age of 1 year; those of the demethyl precursor sterols were 1.5 to 8 times higher in cord blood than in serum at the age of 1 year, suggesting that cholesterol synthesis was markedly increased at birth. Plant sterols, not synthesized in human beings, were already present in serum of all the groups at birth, indicating their transfer, apparently with cholesterol, from mother to fetus. Babies born to FH mothers showed a greater tendency toward accelerated cholesterol synthesis than did those born to FH fathers. Despite signs of markedly high but similar synthesis of cholesterol at birth in FH and non-FH newborns, the diagnosis of FH was questionable by measurement of cholesterol precursors or LDL cholesterol in cord blood. The latter measurement, at the 1-year mark, is superior for diagnostic purposes. (J Lab Clin Med 2002;140:35-42)

Study of cord blood natural killer cell suppressor activity

We tested the immunosuppressive effect of cord blood (CB) natural killer (NK) cells using highly purified CB NK cells in mixed lymphocyte cultures (MLC) containing autologous CB T cells as responders. Control cultures were done without NK cells. Our findings revealed that CB NK cells induced a dose-dependent inhibition of T lymphocyte proliferation as evidenced by decreased 3H-thymidine incorporation in MLC. The T cell alloproliferation was significantly decreased in the presence of an NK cell to responder cell ratio of 0.1, 0.2 or 0.4 compared with control cultures done without NK cells (p=0.02, 0.003 and 0.0002, respectively). T lymphocyte inhibition was also achieved using irradiated CB NK cells and still demonstrable on addition of disparate CB NK and T cells to the MLC. In agreement with previous reports, adult blood NK cells inhibited the alloreactive T cells in the MLC using adult T lymphocytes as responders. Compared to control cultures done without NK cells, statistically significant inhibition of 3H-thymidine incorporation in MLC was observed at a ratio of NK cells to responder cells ratio of 0.2 or 0.4 (p=0.02). To investigate the mechanism whereby CB NK cells can interfere with the development of alloreactive T cells in MLC, we measured the tumour necrosis factor-alpha (TNF-alpha) concentrations in MLC supernatants using NK cell-depleted or unseparated CB mononuclear cells (MNC) as responders. The results revealed significantly high levels of TNF-alpha in the absence of NK cells (p=0.007). We conclude that CB NK cells suppress alloreactive T lymphocytes as do their counterparts in adult blood. However, the high NK to T cell ratio in CB could contribute to a more marked suppressive potential compared to that in adult blood. The mechanism of NK-mediated inhibition is likely related to disruption of the TNF-alpha pathway of T-lymphocyte activation.

Selection of babies for intervention after birth asphyxia

Based on animal experiments, the therapeutic window for neonates with signs of perinatal hypoxia-ischaemia is probably less than 6h, and early selection of patients is of utmost importance. In term neonates, fetal heart rate and blood flow patterns, the Apgar score, and other clinical scoring systems are insufficient to select patients for intervention, whereas umbilical artery pH<7.0 combined with umbilical arteriovenous differences in Pco2, lactate/pyruvate ratios in cord blood, and CSF interleukin-1β have a better predictive value. At present, neurophysiological methods such as (amplitude-integrated) EEG and evoked potentials have the best predictive value. In preterm neonates, lactate/pyruvate and uric acid measurements in cord blood, as well as neurophysiology appear to be helpful to predict brain injury, and might be used to select patients for intervention.