Maternal Erythrocytes Research Articles

The rate of decline in fetal hemoglobin following intrauterine blood transfusion in the management of red cell alloimmunization

ObjectiveHemolytic disease of the fetus and newborn is characterized by fetal anemia, secondary to maternal alloantibody-mediated fetal erythrocyte destruction. Despite our reliance on intrauterine blood transfusion (IUT) to maintain severely affected pregnancies, it remains difficult to predict the fetal response to an infusion of donor blood. Our objective was to determine the daily rate of decline in fetal hemoglobin following one, two, and three transfusions. We also evaluated the relationship between the fetal hemoglobin level and the corresponding doppler measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV). Study DesignA prospective observational study of all singleton pregnancies treated with intrauterine transfusion for fetal anemia secondary to maternal alloimmunization at the National Maternity Hospital, a tertiary referral centre, was conducted over a 10-year period (2011–2020). Demographic and clinical data was obtained from the electronic patient records. Ethical approval was granted by the Ethics and Research Committee of the National Maternity Hospital. ResultsA total of 90 intrauterine blood transfusions were performed in 41 fetuses affected by maternal alloimmunization, of which 70% (n = 29), 34% (n = 14) and 15% (n = 6) required a 2nd, 3rd, and 4th transfusion, respectively. The mean rate of decline in fetal hemoglobin following the first transfusion was 0.4 g/dl/day (range, 0.12–0.64 g/dl/day). The mean rate of decline was lower after repeat transfusions at 0.27 g/dl/day (range, 0.16–0.45 g/dl/day). The sensitivity of MCA-PSV threshold of 1.5 Multiples of the Median (MoM) to detect moderate-severe anaemia declined with rank of IUT, from 82% after one previous transfusion, to 75% after two or more previous transfusions. No fetal mortality was seen in our series. ConclusionKnowledge of the expected rate of decline in fetal hemoglobin following an IUT aids in the determination of appropriate timing of subsequent transfusions in a fetus affected by red cell alloimmunization. We observed a reducing rate of daily decline in hemoglobin in fetuses requiring successive transfusions. Our findings suggest a reduced accuracy of the MCA-PSV threshold of 1.5 MoM in determining the optimal timing of 2nd, 3rd, and 4th transfusions.

Environmental Nanoparticles Reach Human Fetal Brains.

Anthropogenic ultrafine particulate matter (UFPM) and industrial and natural nanoparticles (NPs) are ubiquitous. Normal term, preeclamptic, and postconceptional weeks(PCW) 8–15 human placentas and brains from polluted Mexican cities were analyzed by TEM and energy-dispersive X-ray spectroscopy. We documented NPs in maternal erythrocytes, early syncytiotrophoblast, Hofbauer cells, and fetal endothelium (ECs). Fetal ECs exhibited caveolar NP activity and widespread erythroblast contact. Brain ECs displayed micropodial extensions reaching luminal NP-loaded erythroblasts. Neurons and primitive glia displayed nuclear, organelle, and cytoplasmic NPs in both singles and conglomerates. Nanoscale Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si were detected in placentas and fetal brains. Preeclamptic fetal blood NP vesicles are prospective neonate UFPM exposure biomarkers. NPs are reaching brain tissues at the early developmental PCW 8–15 stage, and NPs in maternal and fetal placental tissue compartments strongly suggests the placental barrier is not limiting the access of environmental NPs. Erythroblasts are the main early NP carriers to fetal tissues. The passage of UFPM/NPs from mothers to fetuses is documented and fingerprinting placental single particle composition could be useful for postnatal risk assessments. Fetal brain combustion and industrial NPs raise medical concerns about prenatal and postnatal health, including neurological and neurodegenerative lifelong consequences.

Associations of Maternal Polyunsaturated Fatty Acids With Telomere Length in the Cord Blood and Placenta in Chinese Population.

Few studies have investigated the correlation between maternal polyunsaturated fatty acids (PUFAs) and telomeres in offspring, and the underlying influential mechanisms. In this study, we assessed the associations of maternal PUFAs with telomere length (TL) and DNA methylation of the telomerase reverse transcriptase (TERT) promoter in the cord blood and the placenta. A total of 274 pregnant women and their newborn babies were enrolled in this study. Maternal blood before delivery, the cord blood, and the placenta at birth were collected. Fatty acids in maternal erythrocytes and cord blood cells were measured by gas chromatography (GC). TL in the cord blood and the placenta was determined using real-time quantitative PCR (qPCR) by calculating the product ratio of telomeric DNA to the single-copy gene β-globin. The TERT promoter methylation was analyzed by DNA bisulfite sequencing. The associations of maternal fatty acids with TL were analyzed by univariate and multivariate regression. We found that low concentrations of docosapentaenoci acid (DPA, C22: 5n-3) and total n-3 PUFAs, adrenic acid (ADA, C22: 4n-6), and osbond acid (OA, C22: 5n-6) and high concentrations of linoleic acid (LA, C18: 2n-6) in maternal erythrocytes were associated with the shortened TL in cord blood cells (estimated difference in univariate analysis −0.36 to −0.46 for extreme quintile compared with middle quintile), and that low concentrations of cord blood docosahexaenoic acid (DHA, C22: 6n-3) were related to the shortened TL in cord blood cells. Differently, high concentrations of α-linolenic acid (LNA, C18: 3n-3), eicosatrienoic acid (EA, C20: 3n-3), DHA, and γ-linoleic acid (GLA, C18:3n-6) in maternal erythrocytes were associated with the shortened TL in the placenta (estimated difference in univariate analysis −0.36 to −0.45 for higher quintiles compared with the middle quintile). Further examination demonstrated that the concentrations of DHA and total n-3 PUFAs in maternal erythrocytes had positive associations with DNA methylation of the TERT promoter in the cord blood instead of the placenta. These data suggest that maternal PUFAs are closely correlated to infant TL and the TERT promoter methylation, which are differently affected by maternal n-3 PUFAs between the cord blood and the placenta. Therefore, keeping higher levels of maternal n-3 PUFAs during pregnancy may help to maintain TL in the offspring, which is beneficial to long-term health.

Human milk fatty acid composition and its association with maternal blood and adipose tissue fatty acid content in a cohort of women from Europe

PurposeHuman milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated.Methods223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother’s blood and cord blood were established.ResultsDuring lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy.ConclusionsThese data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM.

Infant Iodine and Selenium Status in Relation to Maternal Status and Diet During Pregnancy and Lactation.

Iodine and selenium are essential trace elements. Recent studies indicate that pregnant and lactating women often have insufficient intake of iodine and selenium, but the impact on fetal and infant status is unclear. Here, we assessed iodine and selenium status of infants in relation to maternal intake and status of these trace elements in the birth cohort NICE, conducted in northern Sweden (n = 604). Iodine was measured in urine (UIC) in gestational week 29, and in breast milk and infant urine 4 months postpartum, while selenium was measured in maternal plasma and erythrocytes in gestational week 29, and in breast milk and infant erythrocytes 4 months postpartum, in both cases using ICP-MS. Maternal intake was assessed with semi-quantitative food frequency questionnaires in gestational week 34 and at 4 months postpartum. The median intake of iodine and selenium during pregnancy (98 and 40 μg/d, respectively) and lactation (108 and 39 μg/d, respectively) was below recommended intakes, reflected in insufficient status (median UIC of 113 μg/L, median plasma selenium of 65 μg/L). Also, breast milk concentrations (median iodine 77 μg/L, median selenium 9 μg/L) were unlikely to meet infant requirements. Median UIC of the infants was 114 μg/L and median erythrocyte selenium 96 μg/kg, both similar to the maternal concentrations. Infant UIC correlated strongly with breast milk levels (rho = 0.64, p < 0.001). Their erythrocyte selenium correlated with maternal erythrocyte selenium in pregnancy (rho = 0.38, p < 0.001), but not with breast milk selenium, suggesting formation of prenatal reserves. Our results indicate that the transport of iodine and selenium to the fetus and infant is prioritized. Still, it is uncertain whether most infants had sufficient intakes. Further, the results might indicate an involvement of iodine in asthma development during the first year of life, which is essential to follow up. The low maternal and infant dietary intake of both iodine and selenium, especially when the mothers did not use supplements or iodized table salt, suggest a need for a general screening of women and young children.

Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals

BackgroundPrenatal exposure to essential and non-essential metals impacts birth and child health, including fetal growth and neurodevelopment. DNA methylation (DNAm) may be involved in pathways linking prenatal metal exposure and health. In the Project Viva cohort, we analyzed the extent to which metals (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se, and Zn) measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood. We measured metal concentrations in first-trimester maternal erythrocytes, and DNAm in cord blood (N = 361) and mid-childhood blood (N = 333, 6–10 years) with the Illumina HumanMethylation450 BeadChip. For each metal individually, we tested for DMPs using linear models (considered significant at FDR < 0.05), and for DMRs using comb-p (Sidak p < 0.05). Covariates included biologically relevant variables and estimated cell-type composition. We also performed sex-stratified analyses.ResultsPb was associated with decreased methylation of cg20608990 (CASP8) (FDR = 0.04), and Mn was associated with increased methylation of cg02042823 (A2BP1) in cord blood (FDR = 9.73 × 10–6). Both associations remained significant but attenuated in blood DNAm collected at mid-childhood (p < 0.01). Two and nine Mn-associated DMPs were identified in male and female infants, respectively (FDR < 0.05), with two and six persisting in mid-childhood (p < 0.05). All metals except Ba and Pb were associated with ≥ 1 DMR among all infants (Sidak p < 0.05). Overlapping DMRs annotated to genes in the human leukocyte antigen (HLA) region were identified for Cr, Cs, Cu, Hg, Mg, and Mn.ConclusionsPrenatal metal exposure is associated with DNAm, including DMRs annotated to genes involved in neurodevelopment. Future research is needed to determine if DNAm partially explains the relationship between prenatal metal exposures and health outcomes.

Environmental metal exposure and growth to 10 years of age in a longitudinal mother–child cohort in rural Bangladesh

• Life-long Cd exposure was associated to lower WAZ at 10y, especially in boys. • Maternal Cd exposure was linked to diminished growth during childhood. • Concurrent Pb exposure was associated with lower WAZ and HAZ at 10y in boys. • Effect estimates were small, but of relevance in vulnerable populations. Early-life exposure to arsenic (As), cadmium (Cd), and lead (Pb) has been linked to smaller birth and early childhood anthropometry, but little is known beyond the first years in life. To evaluate the impact of gestational and childhood exposures to As, Cd, and Pb on growth up to 10 years of age. We studied 1530 mother–child dyads from a nested sub-cohort of the MINIMat trial in rural Matlab, Bangladesh. Metal concentrations in maternal erythrocytes during pregnancy and in children’s urine at 10y were measured by inductively coupled plasma mass spectroscopy. Child height and weight were measured at 19 occasions from birth until 10y and converted to height-for-age Z-scores (HAZ) and weight-for-age Z-scores (WAZ). Associations between log 2 -transformed metal concentrations and growth parameters were assessed with multivariable-adjusted regression models. Children’s concurrent urinary Cd (median 0.24 µg/L), reflecting long-term exposure, was inversely associated with WAZ (B: −0.072; 95% confidence interval (CI): −0.12, −0.020; p = 0.007), and possibly HAZ (B: −0.046; 95% CI: −0.096, 0.0014; p = 0.057), at 10y. The association with WAZ was stronger in boys than in girls. Maternal erythrocyte Cd (median 0.90 µg/kg) during pregnancy was inversely associated with WAZ during childhood only in boys (B: −0.071, 95% CI: −0.14, −0.0047, p = 0.036). Concurrent urinary Pb (median 1.6 µg/L) was inversely associated with WAZ (B: −0.084; 95% CI: −0.16, −0.0085; p = 0.029) and HAZ (B: −0.087; 95% CI: −0.15, −0.021; p = 0.010) in boys, but not in girls. Neither gestational nor childhood As exposure (median maternal erythrocyte As 4.3 µg/kg and children’s urinary As 57 µg/L) was associated with growth up to 10y. While all effect estimates were small, environmental exposure to Cd and Pb is common and impaired growth is of public health concern, especially for children already at risk of reduced growth due to malnutrition. Gender differences in susceptibility need further investigation.

Early pregnancy exposure to metal mixture and birth outcomes - A prospective study in Project Viva.

Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. To estimate individual and joint effects of metal mixture components on birth outcomes. We used data from 1,391 mother-infant pairs in Project Viva (1999-2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n=729) and head circumference (n=791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3g (95% CI: -79.9, 29.3), 47.9g (95% CI: -98.0, 2.1), and 72.2g (95% CI: -129.8, -14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18cm (95% CI: -0.35, -0.02), 0.10cm (95% CI: -0.25, 0.04), 0.03cm (95% CI: -0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.

Peripartum Investigation of Red Blood Cell Properties in Women Diagnosed with Early-Onset Preeclampsia.

We investigated peripartum maternal red blood cell (RBC) properties in early-onset preeclampsia (PE). Repeated blood samples were taken prospectively for hemorheological measurements at PE diagnosis (n = 13) or during 26–34 weeks of gestation in healthy pregnancies (n = 24), then at delivery, and 72 h postpartum. RBC aggregation was characterized by M index (infrared light transmission between the aggregated RBCs in stasis) and aggregation index (AI—laser backscattering from the RBC aggregates). We observed significantly elevated RBC aggregation (M index = 9.8 vs. 8.5; AI = 72.9% vs. 67.5%; p < 0.001) and reduced RBC deformability in PE (p < 0.05). A positive linear relationship was observed between AI and gestational age at birth in PE by regression analysis (R2 = 0.554; p = 0.006). ROC analysis of AI showed an AUC of 0.84 (0.68–0.99) (p = 0.001) for PE and indicated a cutoff of 69.4% (sensitivity = 83.3%; specificity = 62.5%), while M values showed an AUC of 0.75 (0.58–0.92) (p = 0.019) and indicated a cutoff of 8.39 (sensitivity = 90.9% and specificity = 50%). The predicted probabilities from the combination of AI and M variables showed increased AUC = 0.90 (0.79–1.00) (p < 0.001). Our results established impaired microcirculation in early-onset PE manifesting as deteriorated maternal RBC properties. The longer the pathologic pregnancy persists, the more pronounced the maternal erythrocyte aggregation. AI and M index could help in the prognostication of early-onset PE, but further investigations are warranted to confirm the prognostic role before the onset of symptoms.

Early pregnancy exposure to metals and maternal depressive symptom trajectories in Project Viva

BACKGROUND AND AIM: Exposure to neurotoxicant metals, hypothesized to alter dopaminergic function, have not been sufficiently explored as a risk factor for maternal depression. We evaluated the extent to which early pregnancy blood levels of essential and non-essential metals were prospectively associated with depressive symptom trajectories from mid-pregnancy to 7-years postpartum. METHODS: Participants were 872 women in Project Viva, a longitudinal Boston-area cohort recruited during pregnancy (1999-2002). We measured levels of 11 metal(loid)s (arsenic, barium, cadmium, cesium, copper, mercury, magnesium, manganese, lead, selenium, zinc) in maternal first trimester erythrocytes. We assessed depressive symptoms via the Edinburgh Postnatal Depression Scale at mid-pregnancy and four postpartum timepoints (6 months, 1, 3, 7 years). Utilizing latent class mixed modeling, we identified three depressive symptom trajectories: stable low (86%); elevated perinatal symptoms, then decreasing (9%); and moderate perinatal symptoms, then increasing (5%), among women with ≥3 repeat measures. Adjusting for maternal sociodemographics and dietary intake, we used multinomial logistic regression to test associations of individual metal levels with odds of having an increasing or decreasing trajectory. RESULTS:In our cohort of moderately high socioeconomic status participants (e.g., 75% college graduate), correlations between metal levels were mostly positive (Spearman: 0.01-0.60), except for negative correlations between barium and all other elements. Compared to having a stable low trajectory, a doubling of blood arsenic was associated with 1.27 (95% confidence interval: 1.01, 1.59) odds of an increasing depressive trajectory. Greater prenatal mercury blood level was associated with lower odds of having a decreasing trajectory [0.88 (95% confidence interval: 0.77, 1.00)]. All other first trimester metal levels were not associated with depressive symptom trajectory. CONCLUSIONS:In our study investigating associations of several early pregnancy metals with maternal depressive symptom trajectories, we did not observe strong evidence of associations. Residual confounding or multiple testing may explain observed associations with arsenic and mercury. KEYWORDS: Mental health outcomes, heavy metals, chemical exposures, female

Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: epigenome-wide association study of twelve metals

BACKGROUND AND AIM: Associations between prenatal metal exposure and birth and child health outcomes, including fetal growth and neurodevelopment, may be mediated by changes in DNA methylation (DNAm). We analyzed associations between maternal blood metal(loid)s (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se and Zn) and differential methylated positions (DMPs) at individual CpGs and differentially methylated regions (DMRs) in cord blood, and tested if associations persisted in blood cells collected in middle childhood. METHODS: In the Project Viva cohort, metal(loid) concentrations were measured in first-trimester maternal erythrocytes. DNAm was measured in cord (N=361) and mid-childhood blood cells (N=333, range 6-10 years) using the Illumina HumanMethylation450 BeadChip. DMPs and DMRs were identified using limma and combp, respectively, adjusting for sex, race, gestational age, parity, maternal age, BMI, education, smoking, income, and estimated cell types. Multiple comparisons were adjusted for using a false discovery rate (FDR) correction for DMPs and the Sidak method for DMRs. Sex-stratified analyses were also conducted. RESULTS:Mn was associated with differential methylation of cg02042823 (A2BP1) in cord blood (FDR=9.27x10-6). This association was nominally significant in middle childhood (p=0.009). Mn was associated with 2 and 9 DMPs in male and female infants, respectively (FDR0.05). No other metal(loid)s were associated with cord blood DMPs. All metal(loid)s except Ba and Pb were associated with ≥1 DMR among all infants (Sidak p0.05). Among males, all exposures except Cr, and among females, all exposures except Hg and Pb were associated with ≥1 DMR. DMRs annotated to genes in the chr6 human leukocyte antigen (HLA) region were identified for Cr, Cs, Hg, Mg, and Mn. CONCLUSIONS:Prenatal metal(loid) exposure is associated with DNAm, including DMRs in the HLA region. Future research is needed to assess whether epigenetic associations partially explain the relation of prenatal metal exposures to health outcomes. KEYWORDS: children's environmental health, heavy metals, environmental epidemiology, epigenomics

Maternal and Cord Blood Saturated Fatty Acid Level and Infant Adiposity

This study aimed to assess SFAs profiles in the maternal and cord blood, and the relationship of both SFAs levels with infant adiposity. As many as 99 mothers with singleton pregnancy and pre-pregnancy BMI .18.5 agreed to join the research and completed the data collection process. Maternal and cord blood erythrocyte SFAs profile was analyzed using Gas Chromatography-Flame Ionized Detector. Infant birth weight was measured at birth, while infant skinfolds were at 5.7 days postpartum. We used Aris et al. (2013) equation to assess the infant fat mass. The average maternal age was 29.62}5.84 years old, while the pre-pregnancy BMI was 22.87}3.90 kg/m2. Infant birth weight was 3168.83}341.64 g, and fat mass was 9.39}3.52 %. Maternal total SFAs and palmitic acid (C16:0) concentration were higher than cord blood, while lignoceric acid (C24:0) was lower (p<0.05). Increased maternal caproic (C6:0), capric (C10:0), and lauric acids (C12:0) were associated with higher infant adiposity (p<0.05). Total SFAs, palmitic (C16:0), stearic (C18:0), and behenic acids (C22:0) in cord blood were negatively associated with infant adiposity (p<0.05). Elevated lauric (C12:0) and myristic (C14:0) acids in cord blood were associated with greater adiposity. In conclusion, we found a different SFAs profile between maternal blood during the third trimester of pregnancy and cord blood. Increased maternal caproic, capric, and lauric acids as well as cord bloodfs lauric and palmitic acids contribute to greater infant adiposity.

Prenatal exposure to a mixture of elements and neurobehavioral outcomes in mid-childhood: Results from Project Viva

BackgroundLead (Pb), manganese (Mn), selenium (Se) and methylmercury (MeHg) can be neurotoxic individually, despite Mn and Se also being essential elements. Little is known about the joint effects of essential and non-essential elements on neurobehavior, particularly for prenatal exposures. ObjectivesTo evaluate associations of prenatal exposure to multiple elements with executive function and neurobehavior in children. MethodsParticipants included 1009 mother-child pairs from the Project Viva pre-birth cohort. We estimated maternal erythrocyte Pb, Mn, Se, and Hg concentrations prenatally. In 6-11-year old children (median 7.6 years), parents and teachers rated children's executive function-related behaviors using the Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite score and behavioral difficulties using the Strengths and Difficulties Questionnaire (SDQ) total difficulties score. We evaluated associations of element mixtures with neurobehavior using Bayesian kernel machine regression (BKMR), multivariable linear regression, and quantile g-computation. ResultsMedian erythrocyte Pb, Mn, Se, and Hg concentrations were 1.1 μg/dL, 33.1 μg/L, 204.5 ng/mL, and 3.1 ng/g, respectively. Findings from BKMR and quantile g-computation models both showed worse (higher) parent-rated BRIEF and SDQ z-scores with higher concentrations of the mixture, although estimates were imprecise. When remaining elements were set at their median within BKMR models, increases in Pb and Se from the 25th to 75th percentile of exposure distributions were associated with 0.08 (95% CI: 0.02, 0.19) and 0.07 (95% CI: 0.03, 0.16) standard deviation increases in parent-rated BRIEF scores, and 0.08 (95% CI: 0.02, 0.17) and 0.05 (95% CI: 0.03, 0.13) standard deviation increases in SDQ scores, respectively. There was no evidence of element interactions. DiscussionAlthough associations were small in magnitude, we found a trend of worsening neurobehavioral ratings with increasing prenatal exposure to an element mixture. However, we may be observing a limited range of dose-dependent impacts given the levels of exposure within our population.

Is it necessary to add the eluate testing to the direct antiglobulin test to improve the detection of maternal erythrocyte alloantibodies?

BACKGROUNDThe screening of umbilical cord blood samples by the Direct Antiglobulin Test (DAT) is the reference tool for the identification of maternal erythrocyte alloantibodies present in erythrocytes; however, its diagnostic usefulness is controversial. OBJECTIVETo evaluate the diagnostic validity, safety, and efficiency of the eluate testing (detection of antibody in erythrocyte eluates by the Indirect Antiglobulin Test/IAT) in cord blood samples for detection of maternal erythrocyte alloantibodies in comparison with the DAT. MATERIALS AND METHODSEvaluation study of diagnostic tests. DAT and eluate testing were performed in 306 cord blood samples from neonates born to mothers admitted at Clínica Somer in Rionegro, Colombia; then, antibodies present in the eluates were identified with erythrocyte panels. Percentage of positive results by DAT and IAT were compared with the Pearson's chi-square test and the agreement between both assays with the Cohen's kappa coefficient. The diagnostic sensitivity, specificity, safety, and efficiency of the eluate testing were calculated, taking into account the use of DAT as an imperfect reference test. RESULTSThe DAT detected alloantibodies in 6.21% of samples and the eluate testing in 14.1 %; the strength of agreement between both tests was moderate (k = 0.56) due to 25 discrepancies. The eluate testing showed sensitivity and specificity of 98.83 % and 92.31 % respectively, and a negative predictive value of 99.9 %. The diagnostic efficiency was sufficient for detection of maternal erythrocyte alloantibodies. The antibodies identified in the erythrocyte eluates were anti-A or anti-B (79.5 %), anti-D (136%), anti-C (2,3%), and anti-Fya (2,3%). CONCLUSIONThe eluate testing in cord blood samples is a valid, safe, and efficient test for the diagnosis of maternal erythrocyte alloantibodies.

432 To determine the rate of decline of fetal hemoglobin following an intrauterine blood transfusion

Hemolytic disease of the fetus and newborn (HDFN) is characterized by fetal anemia, secondary to maternal alloantibody-mediated fetal erythrocyte destruction. While RhD immunoprophylaxis has reduced the requirement for intrauterine blood transfusion (IUT), this procedure remains the cornerstone of treatment for severe fetal anemia. The objective of this study was to calculate the rate of daily decline in fetal haemoglobin (FHb) following IUT for fetal anemia. This was a retrospective review of all patients who underwent IUT for fetal anemia at the National Maternity Hospital, Dublin, a tertiary referral centre, over a 10-year period (2011-2020). Data was analysed and the rate of daily decline was calculated for those after one, two and three IUT procedures. Results are presented in Table 1. A total of 98 intrauterine blood transfusions were performed in 46 fetuses, of which 31/98 (67%) and 16/98 (34.7%) required a second and a third IUT, respectively. The median gestational age (GA) at first IUT was 29+1 weeks (range 17+2-34+5 weeks), and the median GA at second IUT was 29+2 weeks (range: 22+0-34+4 weeks). The median rate of decline in FHb between first and second IUT was 0.442g/dl/day (range: 0.12-1.03g/dl/day). The median GA for a third IUT was 32 weeks (range: 26+2-34+5 weeks). The rate of decline in FHb level between the second and third IUT was 0.291g/dl/day (range: 0.16-0.43g/dl/day). Only 5/98 (10.8%) of cases required a fourth IUT at a median GA of 31+4 weeks (range 30+0-34+0 weeks), with a rate of decline of 0.26g/dl/day (range 0.217-0.317g/dl/day). No fetal or maternal mortality was observed in our series. This study provides guidance as to the rate of FHb decline post a varying number of IUT procedures, and observed a reducing rate of decline following successive transfusions. It also highlights the significant range of decline that exists between patients. Careful fetal monitoring between transfusions must remain a vital part of the management of HDFN.

Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in Offspring.

Maternal diet during pregnancy and lactation may affect the propensity of the child to develop an allergy. The aim was to assess and compare the dietary intake of pregnant and lactating women, validate it with biomarkers, and to relate these data to physician-diagnosed allergy in the offspring at 12 months of age. Maternal diet during pregnancy and lactation was assessed by repeated semi-quantitative food frequency questionnaires in a prospective Swedish birth cohort (n = 508). Fatty acid proportions were measured in maternal breast milk and erythrocytes. Allergy was diagnosed at 12 months of age by a pediatrician specialized in allergy. An increased maternal intake of cow’s milk during lactation, confirmed with biomarkers (fatty acids C15:0 and C17:0) in the maternal blood and breast milk, was associated with a lower prevalence of physician-diagnosed food allergy by 12 months of age. Intake of fruit and berries during lactation was associated with a higher prevalence of atopic eczema at 12 months of age. Our results suggest that maternal diet modulates the infant’s immune system, thereby influencing subsequent allergy development.

Low-level maternal exposure to cadmium, lead, and methylmercury and birth outcomes in a Swedish prospective birth-cohort

Background: Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and methylmercury (MeHg) adversely affects birth anthropometry, but results are inconclusive. Objective: To assess the exposure to Cd, Pb, and MeHg in pregnant women, identify the main dietary sources, and elucidate potential impact on birth anthropometry. Methods: In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n=584), Cd also in urine (n=581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid third trimester. Birth anthropometry data were extracted from hospital records. Results: Bivariate associations appeared non-linear (inverted U-shape). In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd above 0.50 µg/kg (median: 0.29 µg/kg) was significantly associated with reduced birth weight by almost 200 g, and length by 0.7 cm. The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg above 1.0 µg/L (median 1.5 µg/kg, mainly MeHg), was significantly associated with 60 g lighter and 30 cm shorter newborns. Maternal Pb (median 11 µg/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of grains, rice and root vegetables, Pb with tea, coffee and game meat, and Hg with intake of fish. Conclusion: The results showed that low-level maternal Cd and MeHg exposure during pregnancy was associated with poorer birth anthropometry. The indicated positive associations at very low exposure levels, likely reflected food benefits. Further prospective studies in low-level exposed populations are warranted.

Levels of n-3 and n-6 Fatty Acids in Maternal Erythrocytes during Pregnancy and in Human Milk and Its Association with Perinatal Mental Health

Omega-3 long-chain polyunsaturated fatty acid (n-3 FA) status may be associated with mood disorders. Here, we evaluated the potential association between antenatal depression/anxiety and n-3/n-6 FA in (a) maternal erythrocytes and (b) human milk. In addition, we explored associations between n-3/n-6 FA in erythrocytes and in human milk and postpartum depression, while controlling for antenatal depression. Twenty-seven pregnant women diagnosed with a current major depressive disorder (MDD; n = 9), anxiety disorder (AD; n = 10) or a mixed anxiety-depression disorder (MADD; n = 8), and 40 healthy controls were included. n-3/n-6 FA were determined in maternal erythrocytes in gestational week 32 and in human milk in postpartum week 1. In the first week postpartum, the Edinburgh-Postnatal-Depression-Questionnaire was used to assess postpartum depression. Results show that women with M(A)DD had significantly lower erythrocyte levels of total n-3 FA, EPA, DHA and DGLA, and significantly higher n-6 DPA, and n-6:n-3, AA:EPA and n-6 DPA:DHA ratios compared to healthy controls. No significant associations between antenatal depression or anxiety and n-3/n-6 FA in human milk were found. After controlling for antenatal mental health, n-3/n-6 FA in maternal erythrocytes or in human milk were not significantly associated with postpartum depression. In conclusion, antenatal depression, alone or with an anxiety disorder, was associated with lower n-3 FA levels and higher n-6:n-3 FA ratios in maternal erythrocytes during gestation. This study provides some insights into the associations between n-3/n-6 FA levels during pregnancy and lactation and perinatal mental health.

Iron Deficiency Anemia in Pregnancy: Novel Approaches for an Old Problem.

Iron needs increase exponentially during pregnancy to meet the increased demands of the fetoplacental unit, to expand maternal erythrocyte mass, and to compensate for iron loss at delivery. In more than 80% of countries in the world, the prevalence of anemia in pregnancy is > 20% and could be considered a major public health problem. The global prevalence of anemia in pregnancy is estimated to be approximately 41.8%. Undiagnosed and untreated iron deficiency anemia (IDA) can have a great impact on maternal and fetal health. Indeed, chronic iron deficiency can affect the general wellbeing of the mother and leads to fatigue and reduced working capacity. Given the significant adverse impact on maternal-fetal outcomes, early recognition and treatment of this clinical condition is fundamental. Therefore, the laboratory assays are recommended from the first trimester to evaluate the iron status. Oral iron supplementation is the first line of treatment in cases of mild anemia. However, considering the numerous gastrointestinal side effects that often lead to poor compliance, other therapeutic strategies should be evaluated. This review aims to provide an overview of the current evidence about the management of IDA in pregnancy and available treatment options.

Low-level maternal exposure to cadmium, lead, and mercury and birth outcomes in a Swedish prospective birth-cohort

Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 μg/kg) above the spline knot of 0.50 μg/kg was associated with reduced birth weight (B: −191 g; 95% CI: −315, −68) and length (−0.67 cm; −1.2, −0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 μg/kg, mainly MeHg) above 1.0 μg/kg, was associated with decreased birth weight (−59 g; −115, −3.0), and length (−0.29 cm; −0.54, −0.047). Maternal Pb (median 11 μg/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted.