Exposure to maternal hyperglycemia in utero has been associated with adverse metabolic outcomes in offspring. However, few studies have investigated the relationship between maternal hyperglycemia and offspring cortisol levels. We assessed associations of gestational diabetes mellitus (GDM) with cortisol biomarkers in two longitudinal prebirth cohorts: Project Viva included 928 mother–child pairs and Gen3G included 313 mother–child pairs. In Project Viva, GDM was diagnosed in N = 48 (5.2%) women using a two-step procedure (50 g glucose challenge test, if abnormal followed by 100 g oral glucose tolerance test [OGTT]), and in N = 29 (9.3%) women participating in Gen3G using one-step 75 g OGTT. In Project Viva, we measured cord blood glucocorticoids and child hair cortisol levels during mid-childhood (mean (SD) age: 7.8 (0.8) years) and early adolescence (mean (SD) age: 13.2 (0.9) years). In Gen3G, we measured hair cortisol at 5.4 (0.3) years. We used multivariable linear regression to examine associations of GDM with offspring cortisol, adjusting for child age and sex, maternal prepregnancy body mass index, education, and socioeconomic status. We additionally adjusted for child race/ethnicity in the cord blood analyses. In both Project Viva and Gen3G, we observed null associations of GDM and maternal glucose markers in pregnancy with cortisol biomarkers in cord blood at birth (β = 16.6 nmol/L, 95% CI −60.7, 94.0 in Project Viva) and in hair samples during childhood (β = −0.56 pg/mg, 95% CI −1.16, 0.04 in Project Viva; β = 0.09 pg/mg, 95% CI −0.38, 0.57 in Gen3G). Our findings do not support the hypothesis that maternal hyperglycemia is related to hypothalamic–pituitary–adrenal axis activity.

Iron deficiency (ID) in early life is associated with morbidities. Most fetal iron required for infant growth is acquired in the third trimester from maternal iron store. However, how prenatal iron level affects ferritin level in early infancy remains controversial. This study aimed to examine the associations between maternal ferritin levels and cord blood serum ferritin (CBSF) and to compare the ferritin levels between different feeding practices in early infancy. Healthy Chinese mothers with uncomplicated pregnancy and their infants were followed up at 3 months post-delivery for questionnaire completion and infant blood collection. Infants who were predominantly breastfed and those who were predominantly formula fed were included in this analysis. Serum ferritin levels were measured in maternal blood samples collected upon delivery, cord blood and infant blood samples at 3 months of age. Ninety-seven mother–baby dyads were included. Maternal ID is common (56 %) while the CBSF levels were significantly higher than maternal ferritin levels. Only three infants (3 %) had ID at 3 months of age. There were no significant correlations between maternal ferritin levels with CBSF (r 0·168, P = 0·108) nor with infant ferritin levels at 3 months of age (r 0·023, P = 0·828). Infant ferritin levels at 3 months were significantly and independently associated with CBSF (P = 0·007) and birth weight (P < 0·001) after adjusting for maternal age, parity, maternal education, infant sex and feeding practice. In conclusion, maternal ID was common upon delivery. However, maternal ferritin levels were not significantly associated with CBSF concentrations nor infant ferritin concentrations at 3 months of age.

Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.

Lower prenatal exposure to n-3 PUFA relative to n-6 PUFA has been hypothesised to influence allergy development, but evidence remains largely inconsistent. In the Dutch Maastricht Essential Fatty Acid Birth (MEFAB) (n 293) and Greek RHEA Mother–Child (n 213) cohorts, we investigated whether cord blood phospholipid PUFA concentrations are associated with symptoms of wheeze, asthma, rhinitis and eczema at the age of 6–7 years. Information on allergy-related phenotypes was collected using validated questionnaires. We estimated relative risks (RR) and 95 % CI for associations of PUFA with child outcomes using multivariable generalised linear regression models. In pooled analyses, higher concentration of the n-3 long-chain EPA and DHA and a higher total n-3:n-6 PUFA ratio were associated with lower risk of current wheeze (RR 0·61; 95 % CI 0·45, 0·82 per sd increase in EPA+DHA and 0·54; 95 % CI 0·39, 0·75 per unit increase in the n-3:n-6 ratio) and reduced asthma risk (RR 0·50; 95 % CI 0·31, 0·79 for EPA+DHA and 0·43; 95 % CI 0·26, 0·70 for the n-3:n-6 ratio). No associations were observed for other allergy-related phenotypes. The results were similar across cohorts. In conclusion, higher EPA and DHA concentrations and a higher n-3:n-6 fatty acid ratio at birth were associated with lower risk of child wheeze and asthma. Our findings suggest that dietary interventions resulting in a marked increase in the n-3:n-6 PUFA ratio, and mainly in n-3 long-chain PUFA intake in late gestation, may reduce the risk of asthma symptoms in mid-childhood.

Vitamin D deficiency during pregnancy is associated with negative health consequences for mothers and their infants. Data on the vitamin D status of pregnant women in Switzerland are scarce. A three-centre study was conducted in the obstetric departments of Zurich, Bellinzona and Samedan (Switzerland) to investigate the prevalence and determinants of vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D)<50 nmol/l) in 3rd-trimester pregnant women living in Switzerland (n 305), and the correlation between 25(OH)D in pregnant women and their offspring at birth (n 278). Demographic and questionnaire data were used to explore the determinants of vitamin D deficiency. Median concentration of serum 25(OH)D in the third trimester of pregnancy was 46·0 nmol/l (1st–3rd quartiles: 30·5–68·5), representing a 53·4 % prevalence of vitamin D deficiency. 25(OH)D levels in the umbilcal cord blood (median: 50·0 nmol/l; 1st–3rd quartiles: 31·0–76·6) strongly correlated with mothers’ serum 25(OH)D (Spearman’s correlation ρ=0·79, P<0·001). Multivariable logistic regression analysis showed that significant determinants of vitamin D deficiency in pregnant women were centre of study, country of origin, season of delivery and vitamin D supplement intake. Near-term BMI, skin colour, use of sunscreen and mothers’ education, although each not individually significant, collectively improved the ability of the model to explain vitamin D status. Low vitamin D levels were common in this sample of pregnant women and their newborns’ cord blood. Vitamin D supplement intake was the most actionable determinant of vitamin D status, suggesting that vitamin D supplementation during pregnancy should receive more attention in clinical practice.

The probability of a Black African finding a matched unrelated donor for a hematopoietic stem cell transplant is minimal due to the high degree of genetic diversity amongst individuals of African origin. This problem could be resolved in part by the establishment of a public cord blood (CB) stem cell bank. The high prevalence of human immunodeficiency virus (HIV) amongst women attending antenatal clinics in sub-Saharan Africa together with the risk of mother-to-child transmission increases the risk of transplant transmissible infection. In addition to screening the mother in a period inclusive of 7 days prior to the following delivery, we propose that all CB units considered for storage undergo rigorous and reliable screening for HIV. The Ultrio-plus® assay is a highly specific and sensitive test for detecting HIV, hepatitis-B and hepatitis-C viruses in peripheral blood. We validated the Ultrio-plus® assay for analytical sensitivity in detecting HIV in CB at the level of detection of the assay. Until more comprehensive and sensitive methods are developed, the sensitivity and reliability of the Ultrio-plus® assay suggest that it could be used for the routine screening of CB units in conjunction with currently recommended maternal screening to reduce the risk of transplant transmissible infection.

Maternal obesity during pregnancy may influence fetal development and possibly predispose offspring to cardiovascular disease. The aim of the present study was to evaluate the relationship between maternal pre-pregnancy body mass index (BMI) and weight gain during pregnancy, and newborn birth weight, with lipid profile, high-sensitivity C-reactive protein (hs-CRP) and leukocyte in newborns. We performed a cross-sectional study of 245 mothers and their children. Blood was collected from the umbilical vein and assayed for lipid profile, hs-CRP and leukocyte count. Newborns average weight was 3241 g, total cholesterol 53.9 mg/dl, high-density lipoprotein cholesterol (HDL-c) 21.9 mg/dl, low-density lipoprotein cholesterol (LDL-c) 26.2 mg/dl, triglyceride 29.5 mg/dl and leukocytes 13,777/mm3. There was a direct correlation of pre-pregnancy BMI of overweight mothers with total cholesterol (r=0.220, P=0.037) and LDL-c (r=0.268, P=0.011) of newborns. Total cholesterol, LDL-c and HDL-c were higher in pre-term newborns (66.3±19.7, 35.9±14.6 and 25.2±7.7 mg/dl, respectively) that in full-term (52.4±13.1, 25.0±8.7 and 21.5±6.0 mg/dl), with P=0.001, 0.001 and 0.003, respectively. Leukocyte counts were higher in full-term newborns (14,268±3982/mm3) compared with pre-term (9792±2836/mm3, P<0.0001). There was a direct correlation between birth weight and leukocyte counts of newborns (r=0.282, P<0.0001). These results suggest the possible interaction of maternal weight and fetal growth with lipid metabolism and leukocyte count in the newborn, which may be linked to programming of the immune system.

Several studies have shown that South Asian neonates have a characteristic thin–fat insulin-resistant phenotype. The aim of our study was to determine whether this phenotype is also present in South Asians who have migrated to a Western country (the Netherlands). South Asian and white Dutch pregnant women were included in our study. After delivery, cord blood was collected and neonatal anthropometry was measured within 72 h. Compared with white Dutch mothers, South Asian mothers were younger (28.5 v. 32.2 years, P<0.001) and had a higher prepregnancy body mass index (25.1 v. 23.0, P=0.001). Gestational age at delivery was on average 4 days shorter in South Asians (274.9 v. 278.8, P=0.001). To compare the two groups of neonates, we calculated sex- and gestation-specific s.d. scores using the values for mean and s.d. obtained from the white Dutch subjects as a reference. All measurements were smaller in South Asian neonates, except for those of the skinfolds. The largest difference was found in abdominal circumference (s.d. score 1.39, 95% CI −1.76 to −1.01). Triceps and subscapular skinfolds were similar in both groups (triceps s.d. score −0.34, 95% CI −0.88 to +0.20 and subscapular s.d. score −0.03, 95% CI −0.31 to +0.25). South Asian neonates had higher cord plasma levels of triglycerides (0.40 v. 0.36, P=0.614), glucose (5.4 v. 4.8, P=0.079) and insulin (6.3 v. 4.0, P=0.051). However, these differences were not statistically significant. After adjustment for birth weight, the difference in insulin became statistically significant (P=0.001). We therefore conclude that the thin–fat insulin-resistant phenotype is also present in South Asian neonates in the Netherlands.

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.

There is increasing evidence of an association between a low maternal vitamin D status and a high risk of adverse pregnancy outcomes. In a cross-sectional study, we investigated the vitamin D status of pregnant women to determine potentially influencing factors. Between December 2010 and February 2012, 261 maternal blood samples and 328 cord blood samples were collected for the analysis of 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone, alkaline phosphatase and Ca concentrations. Demographical characteristics and clinical data were recorded by a questionnaire and from medical files. The overall median maternal and cord blood 25(OH)D levels were 25·0 (interquartile range 12·6–45·5) nmol/l and 34·1 (interquartile range 17·7–58·6) nmol/l, respectively. During the winter months, 98 % of the maternal blood samples and 94 % of the cord blood samples had 25(OH)D levels < 50 nmol/l. In the summer months, 49 % of the women and 35 % of the cord blood samples were vitamin D deficient. Using logistic regression models, significant risk factors for maternal vitamin D deficiency were found to be physical inactivity (adjusted OR (aOR) 2·67, 95 % CI 1·06, 6·69, P= 0·032) and a non-European country of origin (aOR 3·21, 95 % CI 1·0, 10·28, P= 0·047) after controlling for season and independent risk factors. These results are the first 25(OH)D data for pregnant women in Germany. They indicate the need for urgent implementation of strategies to prevent vitamin D deficiency by healthcare authorities that are in charge of preventing vitamin D deficiency, especially during these sensitive stages of life.

Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for brain growth and visual and cognitive development and is provided by materno–fetal placental transfer. We recently showed that maternal fatty acid desaturase (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS genotypes influence the amounts of umbilical cord fatty acids has not been investigated until now. The aim of the present study was to investigate the influence of maternal and child FADS genotypes on the amounts of LC-PUFA in umbilical cord venous plasma as an indicator of fetal fatty acid supply during pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed for association with seventeen FADS gene cluster SNP in over 2000 mothers and children from the Avon Longitudinal Study of Parents and Children. In a multivariable analysis, the maternal genotype effect was adjusted for the child genotype and vice versa to estimate which of the two has the stronger influence on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically, most analysed maternal SNP were associated with cord plasma levels of the precursor n-6 PUFA, whereas the child genotypes were mainly associated with more highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty acids suggests that fetal LC-PUFA status is determined to some extent by fetal fatty acid conversion. Associations of particular haplotypes suggest specific effects of SNP rs498793 and rs968567 on fatty acid metabolism.

Events and exposures in pregnancy can have critical effects on fetal development with lasting implications for subsequent health and disease susceptibility. There is growing interest in how modern environmental changes influence fetal immune development and contribute to the recent epidemic of allergy and other immune disorders. Rising rates of allergic disease in early infancy, together with pre-symptomatic differences in immune function at birth, suggest that antenatal events play a predisposing role in the development of disease. A number of environmental exposures in pregnancy can modify neonatal immune function including diet, microbial exposure and maternal smoking, and there is emerging evidence from animal models that these factors may have epigenetic effects on immune gene expression and disease susceptibility. Furthermore, functional genetic polymorphisms also alter individual vulnerability to the effects of these environmental exposures, highlighting the complexity of gene–environmental interactions in this period. All these observations underscore the need for ongoing research to understand the pathogenesis and rising incidence of disease in the hope of better strategies to reverse this.

Objective. Maternal infection has been considered to be a risk factor for filarial infection in offspring. In order to examine the influence of maternal infection in neonates, we have determined the prevalence of circulating filarial antigen (CFA) and anti-filarial antibodies in 119 maternal and corresponding cord blood samples collected from an area endemic for bancroftian filariasis. Method. Prevalence of antigenaemia was detected using Og4C3 circulating filarial antigen enzyme-linked immunosorbent assay. The presence of microfilariae was determined by filtration of a 1 ml sample through a Nuclepore membrane. Antibody isotypes (IgG, IgM, and IgE) to filarial antigen (Setaria digitata antigenic extract) were determined by enzyme linked immunosorbent assay (ELISA). Results. Microfilariae were detected in 14 cases (11·8%), whereas the Og4C3 assay could detect filarial antigen in 44·5% of pregnant mothers. Interestingly, 24·5% of samples born from CFA-positive mothers were found positive for CFA. None of the cord samples from CFA-negative mothers were found positive for CFA. No significant difference was observed in prevalence of filarial-specific IgG, IgM and IgE antibodies in CFA-positive and negative mothers. IgG antibody was detected in 60·5% of maternal and 21·8% of cord samples. IgG antibody in the cord does not differ with the antigen status of the mother. In contrast IgM and IgE antibody prevalence was significantly higher in cord from infected mothers than non-infected mothers (11·3% vs 0 for IgM, 24·5% vs 3·03% for IgE). Conclusion. Our study demonstrates the transplacental transfer of circulating filarial antigen from mother to cord. Filaria-specific IgM and IgE antibodies were higher in cord blood from infected mothers than from non-infected mothers. The findings of the study provide additional circumstantial evidence for pre-natal sensitization to filarial antigens developed in utero.

Oral folic acid above certain threshold doses results in unmetabolised folic acid in serum. This raises a number of public health safety issues, principally the potential to mask pernicious anaemia; more recently the theoretical potential for high-dose folic acid to promote cancer has been highlighted. In this paper we set out to examine the appearance of unmetabolised folic acid both in cord blood from newborn full-term and premature infants and serum from 4-d-old infants post-formula feeding. Blood was collected from the umbilical cord of eleven infants in the delivery room immediately after birth. A follow-up serum sample (n 9) was collected 4d later from infants post-formula feeding. We detected unmetabolised folic acid in cord blood from all infants at birth. In addition, unmetabolised folic acid was present in serum of seven infants post-formula feeding, six of which had increased from birth. Our results imply that infants in Ireland, which does not yet have mandatory fortification, could potentially have circulatory unmetabolised folic acid at the time of birth. We do not know if the presence of folic acid in cord blood will have any adverse consequences. However, if theoretical safety concerns are borne out by future research, the likelihood is that the longer the exposure the more likely the potential for harm. This would also be the case in infants exposed to unmetabolised folic acid as a result of formula feeding.

Objectives: To compare outcome attributes of three available technologies for stem cell transplantation—bone marrow transplantation (BM), peripheral blood cell transplantation (PB), and cord blood transplantation (CB). To compare the cost per recipient for the three technologies, incorporating all donor and antigen matching functions, as well as the transplantation procedures.

Methods: Review of relevant literature using the CancerLit and HealthSTAR databases (plus earlier searches of MEDLINE and Embase) to summarize outcome differences. Estimations of cost per transplant using models drawing on Canadian experience.

Results: The literature review indicated that PB may have a modest advantage over BM in terms of outcomes. The literature indicated that CB has longer engraftment times (although this may be due to inadequate controls). Our modeling exercise indicated that costs for PB and BM are similar. CB has a higher cost per recipient, due in large part to the higher testing costs for every donated unit.

Conclusions: Current literature is inadequate to provide an outcomes comparison of CB, PB, and BM. Viewed from a system-wide perspective, CB is a higher cost technique. However, PB and CB are emerging as technologies, and so our results should be viewed alongside the notion that there may be a steep learning curve in these technologies.