Associations between Longitudinal Maternal and Cord Blood Vitamin D Status and Child Growth Trajectories Up to 4 Years of Age.

The current study aimed to explore the combined and individual effects of vitamin D (VitD) status in three trimesters during pregnancy and cord blood (CB) on child growth trajectories from birth to 4 years of age. Pregnant women (n = 1100) were recruited between 2013 and 2016 in the Shanghai Birth Cohort (SBC) Study. A total of 959 mother-child dyads were included. VitD status was measured by LC-MS/MS at three trimesters (T1, T2, T3) and CB. Children's weight, length/height, and head circumference were assessed at birth, 42 days, 6, 12, 24 months, and 4 years of age, and standardized into z-scores [weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HCZ) and weight-for-length z-score (WLZ)]. Using the group-based trajectory model (GBTM), the trajectories of the four growth parameters were categorized into discrete groups. The generalized estimating equation (GEE) was employed to analyze the mixed effect of 25(OH)D throughout pregnancy on growth trajectories. The association between 25(OH)D status and each growth trajectory group was examined by multivariable logistic regression. Each 10 ng/mL increase in 25(OH) throughout three trimesters was not associated with four anthropometric parameters. Each 10 ng/mL increase in VitD in T3 was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.75; 95% CI: 0.62, 0.91; p < 0.01). Each 10 ng/mL increase in VitD in CB was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.57; 95% CI: 0.43, 0.76; p < 0.01). No significant association was found between maternal or CB VitD and LAZ or HCZ. Three trimesters' VitD throughout pregnancy had no persistent effect on the offspring's growth trajectory. However, higher VitD status in the third trimester and CB related to a lower risk of high-increasing WAZ from birth to 4 years of age. Elevated VitD levels in late pregnancy and cord blood may protect against continuous early-life weight growth at high levels.

Association of maternal and cord vitamin B12 levels with anthropometry in term neonates born to malnourished mothers in coastal South India.

Background: Malnourished pregnant women are at increased risk of micronutrient deficiency. We assessed the vitamin B12 status in both malnourished and normally nourished pregnant women and their neonates. Additionally, we studied the association between maternal B12 levels, cord B12 levels and neonatal anthropometry. Methods: This cross-sectional study enrolled 63 malnourished and 63 normally nourished mothers and neonates. Maternal and cord blood samples were collected at the time of delivery for estimation of vitamin B12 levels. Maternal and cord vitamin B12 levels were compared using the Mann-Whitney U test. Neonatal anthropometry was correlated with maternal and cord B12 levels using Spearman's correlation. Data were analyzed using SPSS version 25. Results: Mean maternal age was 26.58 yrs. The median cord B12 levels were lower than the maternal B12 levels. Maternal B12 levels showed a strong positive correlation with cord B12 levels (rho = 0.879; p < 0.001). Maternal (p < 0.001) and cord (p < 0.001) vitamin B12 levels were significantly lower in the malnourished group than in the normally nourished group. In malnourished group, 66.8% mothers and 95.2% neonates were Vitamin B12 deficient, whereas 1.5% mothers and 4.7% neonates were vitamin B12 deficient in normally nourished group. In the malnourished group, maternal B12 levels were positively correlated with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p =0.008), whereas cord B12 levels were positively correlated with birth weight in the normally nourished group. (rho 0.277 p= 0.028). Conclusion: High rates of vitamin B12 deficiency were observed in malnourished mothers and neonates. There was a positive correlation between birth weight, length, and maternal vitamin B12 levels in malnourished mothers. These findings emphasize the need to address maternal malnutrition and vitamin B12 deficiency to improve neonatal health.

An investigation of the umbilical artery N-terminal proBrain natriuretic peptide levels of fetuses due to fetal distress in term pregnancies.

OBJECTIVE: This study aimed to investigate umbilical artery N-terminal proBrain natriuretic peptide (NT-proBNP) in fetuses delivered by cesarean section due to fetal distress in term pregnancies. METHODS: This prospective case-control study was conducted at the Antalya Training and Research Hospital Obstetric Department, Turkiye. A total of 140 pregnant women, 70 underwent elective cesarean sections between weeks 37 and 40 of gestation (Group 1, the control group) and 70 underwent cesarean sections due to fetal distress (Group 2, the study group), were included. The participants' sociodemographic and obstetric data and fetal umbilical blood NT-proBNP levels were recorded in a database. RESULTS: Age, body mass index, gestational age, prenatal diagnostic tests, fetal anatomical scanning, and baby gender ratios were comparable between the groups (p>0.05), while statistically significant differences were observed in terms of gravidity (3.0 vs. 1.0, p≤0.001) and parity numbers (2 vs. 0, p≤0.001), baby height (50.36±0.88 vs. 49.80±0.86, p≤0.001) and weight (3422.43±409.16 vs. 3239.86±293.74, p=0.003), 1-min Apgar (9.0±0.1 vs. 8.5±1.3, p≤0.001) and 5-min Apgar (10.0±0.1 vs. 9.8±0.4, p=0.026) scores, umbilical artery pH (7.32±0.05 vs. 7.25±0.07, p≤0.001), umbilical artery base deficit (-2.48±1.23 vs. -4.36±1.09. p≤0.001), and NT-proBNP levels [8.77 (7.72-9.39) vs. 12.35 (9.69-12.92), p<0.001]. CONCLUSION: This study showed that NT-proBNP can be used as an important marker in the diagnosis of fetal distress. Prospective studies with more participants are now needed to confirm the accuracy of our results.

Pre-pregnancy overweight or obesity moderates the association between prenatal maternal depressive symptoms and infant cord blood omega-3 levels.

BACKGROUND: Empirical evidence has demonstrated associations between pre-pregnancy obesity and perinatal maternal depressive symptoms. Omega-3 is an essential fatty acid derived from dietary sources that is critical for fetal brain development. Pre-pregnancy obesity is associated with higher omega-3 intake, but a weaker association between dietary intake and respective maternal and cord blood omega-3 levels. Further, lower intake of omega-3 during pregnancy has been linked to higher depressive symptoms. Yet, prior studies have not examined the interactive effects of pre-pregnancy overweight or obesity (OWOB) and prenatal maternal mental health symptoms on infant cord blood omega-3 levels. METHODS: Participants included 394 maternal-infant dyads from the NIH Environmental influences on Child Health Outcomes (ECHO) - Safe Passage Study in South Dakota. A pre-pregnancy body mass index (BMI) > 25 was used to dichotomize participants as OWOB (54%) vs. non-OWOB (46%). Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) and prenatal maternal anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). We implemented linear regression models to examine the interaction term between pre-pregnancy BMI category and prenatal maternal mental health symptoms on cord blood omega-3 levels. Secondary analyses were stratified by pre-pregnancy BMI category. RESULTS: We observed a significant interaction between pre-pregnancy BMI category and prenatal maternal depressive symptoms with cord blood omega-3 (F(4,379) = 6.21, p < .0001, adj. R2 = 0.05). Stratified models revealed an association between prenatal maternal depressive symptoms with lower cord blood omega-3 levels only among individuals with pre-pregnancy OWOB (ß = -0.06, 95% CI = -0.11, -0.02; F (2,208) = 4.00, p < .05, adj R2 = 0.03). No associations were observed among non-OWOB participants. CONCLUSIONS: Findings suggest maternal-placental transfer of omega-3 may represent one pathway by which maternal metabolic and mental health impacts infant development.

Gestational DNA methylation age as a marker for fetal development and birth outcomes: findings from the Boston Birth Cohort.

BACKGROUND: Gestational DNA methylation age (GAmAge) has been developed and validated in European ancestry samples. Its applicability to other ethnicities and associations with fetal stress and newborn phenotypes such as inflammation markers are still to be determined. This study aims to examine the applicability of GAmAge developed from cord blood samples of European decedents to a racially diverse birth cohort, and associations with newborn phenotypes. METHODS: GAmAge based on 176 CpGs (Haftorn GAmAge) was calculated for 940 children from a US predominantly urban, low-income, multiethnic birth cohort. Cord blood DNA methylation was profiled by Illumina EPIC array. Newborn phenotypes included anthropometric measurements and, for a subset of newborns (N = 194), twenty-seven cord blood inflammatory markers (sandwich immunoassays). RESULTS: GAmAge had a stronger correlation with GEAA in boys (r = 0.89, 95% confidence interval (CI) [0.87,0.91]) compared with girls (r = 0.83, 95% CI [0.80,0.86]), and was stronger among extremely preterm to very preterm babies (r = 0.91, 95% CI [0.81,0.96]), compared with moderate (r = 0.48, 95% CI [0.34,0.60]) and term babies (r = 0.58, 95% CI [0.53,0.63]). Among White newborns (N = 51), the correlation between GAmAge vs. GEAA was slightly stronger (r = 0.89, 95% CI [0.82,0.94]) compared with Black/African American newborns (N = 668; r = 0.87, 95% CI [0.85,0.89]) or Hispanic (N = 221; r = 0.79, 95% CI [0.74,0.84]). Adjusting for GEAA and sex, GAmAge was associated with anthropometric measurements, cord blood brain-derived neurotrophic factor (BDNF), and monocyte chemoattractant protein-1 (MCP-1) (p < 0.05 for all). CONCLUSIONS: GAmAge estimation is robust across different populations and racial/ethnic subgroups. GAmAge may be utilized as a proxy for GEAA and for assessing fetus development, indicated by inflammatory state and birth outcomes.

Cord blood vitamin A and vitamin D levels in relation to physical growth in exclusively breastfed infants aged 0-6 months.

Background: Vitamins A and D are essential for the health of pregnant women and infants. Nevertheless, the relationship between umbilical cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants remains uncertain. Objective: This cohort study aims to examine the relationship between cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants aged 0-6 months. Methods: 140 singleton mother-infant pairs were recruited in total. Questionnaires were used to collect maternal and infant information, and liquid chromatography was utilized to quantify the levels of vitamins A and D in the umbilical cord blood. Anthropometric measurements were conducted at birth, at 3 and 6 months of age, and the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HAZ), and BMI-for-age z-score (BMIZ) were calculated. Univariate and multivariate linear regression models were used for the analysis. Results: The average concentration of vitamins A and D in cord blood was 0.58 ± 0.20 µmol/L and 34.07 ± 13.35 nmol/L, both below the normal range for children. After adjusting for confounding factors, vitamin A levels in cord blood positively correlated with HAZ growth in infants aged 3-6 months (ß= 0.75, P < 0.01) while vitamin D levels negatively correlated with LAZ growth (ß= -0.01, P = 0.01) and positively correlated with BMIZ growth (ß= 0.02, P < 0.01). Conclusion: Higher Vitamin A levels at birth promote HAZ growth in infants aged 3-6 months while higher vitamin D levels at birth promote BMIZ growth in infants aged 3-6 months. Clinical trial registration: https://register.clinicaltrials.gov, identifier NCT04017286.

Umbilical Cord pH Levels and Neonatal Morbidity and Mortality.

Importance: Umbilical cord pH (UC-pH) level is an important objective indicator of intrapartum fetal hypoxia and is used to predict neonatal morbidity and mortality. A UC-pH value of less than 7.00 is often defined as a threshold for severe acidosis, but existing evidence is divergent and largely based on UC-pH measurements from selected populations; consequently, the results are challenging to interpret. Objective: To investigate the association between UC-pH levels and the risk of adverse neonatal outcomes in a national setting with universal UC-pH measurement. Design, Setting, and Participants: This national, population-based cohort study included all liveborn, singleton, full-term infants without malformations born in Denmark from January 1, 2012, to December 31, 2018. Data were analyzed from January 1, 2023, to March 1, 2024. Exposure: Umbilical cord pH level categorized as less than 7.00, 7.00 to 7.09, 7.10 to 7.19 and 7.20 to 7.50 (reference group). Main Outcomes and Measures: The primary outcome was a composite of severe adverse neonatal outcomes: neonatal death, therapeutic hypothermia, mechanical ventilation, treatment with inhaled nitric oxide, or seizures. Secondary outcomes were individual components of the primary outcome, Apgar score, respiratory outcomes, and hypoglycemia. Data are presented as adjusted risk ratios (ARRs) with 95% CIs. Results: Among the 340 431 infants included, mean (SD) gestational age was 39.9 (1.6) weeks; mean (SD) birth weight was 3561 (480) g; and 51.3% were male. Umbilical cord pH of less than 7.20 was observed more often among infants with a gestational age of 40 or 41 weeks (31.6%-33.6% compared with 18.2%-20.2% at a gestational age of 39 weeks) and among male infants (53.9%-55.4% vs 44.6%-46.1% among female infants). Compared with the pH reference group (576 of 253 540 [0.2%]), the risk for the primary outcome was increased for the groups with UC-pH levels of less than 7.00 (171 of 1743 [9.8%]), 7.00 to 7.09 (101 of 11 904 [0.8%]), and 7.10 to 7.19 (259 of 73 244 [0.4%]). Comparable patterns were observed for the individual outcomes, except for neonatal death, which was only increased in the group with UC-pH levels of less than 7.10. The risk of treatment with continuous positive airway pressure was increased when UC-pH levels were less than 7.20, and the risk of hypoglycemia was 21.5% if UC-pH levels were less than 7.10. Conclusions and Relevance: In this cohort study of 340 431 newborn infants, results support and extend previous studies indicating a higher risk of adverse outcomes even at UC-pH levels above 7.00. The threshold for more intensive observation and treatment may be reconsidered.

Fluoride-related changes in the fetal cord blood proteome; a pilot study.

BACKGROUND: Fluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA. OBJECTIVE: To identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women. METHODS: The proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes. RESULTS: Pathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation. CONCLUSION: Maternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration.

Exploring the levels of persistent organic pollutants in umbilical cord blood and their connection to gestational age and birth weights in Sanliurfa, Turkey.

BACKGROUND: Controversy surrounds the impact of persistent organic pollutants (POPs) on fetal development. This study aimed to investigate levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in umbilical cord blood from Sanliurfa mothers in Turkey, exploring associations with gestational age and birth weight. METHODS: Participants included voluntary mothers pregnant with a single fetus, providing details on maternal factors. Cord blood samples were collected immediately after delivery. Samples were extracted with a modified QuEChERS method, and OCPs (17 pesticides) and PCBs (11 congeners) compound levels were analyzed with a gas chromatograph/mass spectrometry. Detection frequencies and levels of POPs by single pollutant type and pollutant groups were calculated and compared according to gestational duration and birth weight. We used partial least squares discriminant analysis to identify the key chemicals and distinguish their respective statuses. RESULTS: Among 120 infants, 35 were preterm but appropriate for gestational age, 35 were term but small for gestational age (SGA), and 50 were term and appropriate for gestational age (AGA). Beta HCH, Oxy-Chlordan, and PCB 28, were not detected in cord blood samples. Half of the samples contained at least 4 types of OCPs, with a median OCP level of 38.44 ng/g. Among the DDT, 2,4'-DDE was found at the highest concentration in cord plasma samples. The PCB congeners with a frequency exceeding 50% were ranked in the following order: 151, 149, 138, 146. The median level of ∑PCBs was 5.93 ng/g. Male infants born at term with SGA status exhibited lower levels of ∑DDTs, ∑OCPs compared to male infants born preterm or at term with AGA status. Di-ortho-substituted PCBs and hexachlorinated PCBs were higher in male infants born at term with SGA status than male infants born preterm with AGA status. CONCLUSION: Overall, exposure to DDT and PCBs demonstrates varying effects depending on gestational duration and birth weight, with exposure levels also differing by gender. This underscores the necessity for studies across diverse populations that investigate the combined effects of multiple pollutant exposures on gestational age, birth weight, and gender simultaneously.

Impact of Maternal Pre-Pregnancy Underweight on Cord Blood Metabolome: An Analysis of the Population-Based Survey of Neonates in Pomerania (SNiP).

Intrauterine growth restriction leads to an altered lipid and amino acid profile in the cord blood at the end of pregnancy. Pre-pregnancy underweight is an early risk factor for impaired fetal growth. The aim of this study was to investigate whether a pre-pregnancy body mass index (ppBMI) of <18.5 kg/m2, as early as at the beginning of pregnancy, is associated with changes in the umbilical cord metabolome. In a sample of the Survey of Neonates in Pomerania (SNIP) birth cohort, the cord blood metabolome of n = 240 newborns of mothers with a ppBMI of <18.5 kg/m2 with n = 208 controls (ppBMI of 18.5-24.9 kg/m2) was measured by NMR spectrometry. A maternal ppBMI of <18.5 kg/m2 was associated with increased concentrations of HDL4 cholesterol, HDL4 phospholipids, VLDL5 cholesterol, HDL 2, and HDL4 Apo-A1, as well as decreased VLDL triglycerides and HDL2 free cholesterol. A ppBMI of <18.5 kg/m2 combined with poor intrauterine growth (a gestational weight gain (GWG) < 25th percentile) was associated with decreased concentrations of total cholesterol; cholesterol transporting lipoproteins (LDL4, LDL6, LDL free cholesterol, and HDL2 free cholesterol); LDL4 Apo-B; total Apo-A2; and HDL3 Apo-A2. In conclusion, maternal underweight at the beginning of pregnancy already results in metabolic changes in the lipid profile in the cord blood, but the pattern changes when poor GWG is followed by pre-pregnancy underweight.

Association of cord blood Ang-1 and sCD105 levels with bronchopulmonary dysplasia in preterm infants.

BACKGROUND: To investigate the relationship between cord blood levels of Angiopoietin-1 (Ang-1) and S-endoglin (sCD105) and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Sixty-one preterm infants admitted to the neonatal intensive care unit of the study hospital between July 2021 and September 2022 were included. Cord blood was collected after the birth of premature infants. Ang-1 and sCD105 levels were quantified using the vascular endothelial growth factor enzyme-linked immunosorbent assay. Preterm infants were divided into BPD and non-BPD groups, and differences in Ang-1 and sCD105 levels between the two groups were compared. A binary logistic model was used to assess the association between low and high levels Ang-1 and BPD in preterm infants. RESULTS: In the study, there were 20 preterm infants with BPD (32.8%) and 41 preterm infants with non-BPD (67.2%). Ang-1 concentration levels were lower in the BPD group than in the non-BPD group (7105.43 (5617.01-8523.00) pg/ml vs. 10488.03 (7946.19-15962.77) pg/ml, P = 0.027). However, the sCD105 concentration levels were not significantly different between the BPD and non-BPD groups (P = 0.246). A median Ang-1 concentration of 8800.40 pg/ml was calculated. Logistic regression analysis showed that after adjusting for gestational age, birth weight, and maternal prenatal steroid hormone application, the odds ratio (OR) was 8.577 for the risk of BPD in preterm infants with Ang-1 concentrations of ≤ 8800.40 pg/ml compared to those with Ang-1 concentrations of > 8800.40 pg/ml (OR: 8.577, 95% confidence interval: 1.265-58.155, P = 0.028). CONCLUSION: Our study indicated that Ang-1 levels in the cord blood of preterm infants may be associated the risk of BPD. In the future, we will continue to conduct study with large samples.

Associations between prenatal exposure to per- and polyfluoroalkyl substances and plasma immune molecules in three-year-old children in China.

BACKGROUND: Many studies have reported that prenatal exposure to Per- and Polyfluoroalkyl Substances (PFASs) can disrupt immune function. However, little is known about the effects of PFASs on immune molecules. The study analyzed the association between prenatal exposure to mixed and single PFASs and plasma immune molecules in three-year-old children. METHODS: Ten PFASs were measured in umbilical cord serum, while peripheral blood samples were collected at age three to measure immune molecules. Associations between exposure to individual and combined PFASs and immune molecules were analyzed using Generalized Linear Models and Weighted Quantile Sum (WQS) regression. RESULTS: (1) Interleukin-4 (IL-4) increased by 23.85% (95% CI:2.99,48.94) with each doubling of Perfluorooctanoic Acid (PFOA), and Interleukin-6 (IL-6) increased by 39.07% (95%CI:4.06,85.86) with Perfluorotridecanoic Acid (PFTrDA). Elevated PFOA and Perfluorononanoic Acid (PFNA) were correlated with increases of 34.06% (95% CI: 6.41, 70.28) and 24.41% (95% CI: 0.99, 53.27) in Eotaxin-3, respectively. Additionally, the doubling of Perfluorohexane Sulfonic Acid (PFHxS) was associated with a 9.51% decrease in Periostin (95% CI: -17.84, -0.33). (2) The WQS analysis revealed that mixed PFASs were associated with increased IL-6 (ß = 0.37, 95%CI:0.04,0.69), mainly driven by PFTrDA, PFNA, and 8:2 Chlorinated Perfluoroethyl Sulfonamide (8:2 Cl-PFESA). Moreover, mixed PFASs were linked to an increase in Eotaxin-3 (ß = 0.32, 95% CI: 0.09,0.55), primarily influenced by PFOA, PFTrDA, and Perfluorododecanoic Acid (PFDoDA). CONCLUSIONS: Prenatal PFASs exposure significantly alters the levels of immune molecules in three-year-old children, highlighting the importance of understanding environmental impacts on early immune development.

Post-natal gestational age assessment using targeted metabolites of neonatal heel prick and umbilical cord blood: A GARBH-Ini cohort study from North India.

Background: Accurate assessment of gestational age (GA) and identification of preterm birth (PTB) at delivery is essential to guide appropriate post-natal clinical care. Undoubtedly, dating ultrasound sonography (USG) is the gold standard to ascertain GA, but is not accessible to the majority of pregnant women in low- and middle-income countries (LMICs), particularly in rural areas and small secondary care hospitals. Conventional methods of post-natal GA assessment are not reliable at delivery and are further compounded by a lack of trained personnel to conduct them. We aimed to develop a population-specific GA model using integrated clinical and biochemical variables measured at delivery. Methods: We acquired metabolic profiles on paired neonatal heel prick (nHP) and umbilical cord blood (uCB) dried blood spot (DBS) samples (n = 1278). The master data set consists of 31 predictors from nHP and 24 from uCB after feature selection. These selected predictors including biochemical analytes, birth weight, and placental weight were considered for the development of population-specific GA estimation and birth outcome classification models using eXtreme Gradient Boosting (XGBoost) algorithm. Results: The nHP and uCB full model revealed root mean square error (RMSE) of 1.14 (95% confidence interval (CI) = 0.82-1.18) and of 1.26 (95% CI = 0.88-1.32) to estimate the GA as compared to actual GA, respectively. In addition, these models correctly estimated 87.9 to 92.5% of the infants within ±2 weeks of the actual GA. The classification models also performed as the best fit to discriminate the PTB from term birth (TB) infants with an area under curve (AUC) of 0.89 (95% CI = 0.84-0.94) for nHP and an AUC of 0.89 (95% CI = 0.85-0.95) for uCB. Conclusion: The biochemical analytes along with clinical variables in the nHP and uCB data sets provide higher accuracy in predicting GA. These models also performed as the best fit to identify PTB infants at delivery.

Maternal APOE ε2 as a possible risk factor for elevated prenatal Pb levels.

Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (ɛ2, ɛ3, ɛ4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics. We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype. The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58-87.6) and 9.31 (1.82-47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure.

Lead in umbilical cord blood and associated factors in Casablanca Morocco: A preliminary results.

BACKGROUND: Lead is the most common toxic metal to which Moroccans are exposed. Given the susceptibility of the fetus to lead, it is crucial to assess prenatal lead exposure. However, in Morocco, no study has assessed prenatal exposure to lead. The main goals of the present study are to determine lead concentration in umbilical cord blood and identify risk factors for prenatal lead exposure in Casablanca, Morocco. METHODS: To achieve these purposes, 87 cord blood lead samples were collected from mothers-baby pairs from January to December 2019. Indeed, a structured questionnaire was used to collect socio-demographic characteristics, obstetric data, leisure, cultural habits, and environmental information. Cord blood lead level was analyzed by inductively coupled plasma-mass spectrometry. RESULTS: The median lead concentration was 4.902 µg/dl with a minimum and maximum of 0.833 µg/dl and 23.593 µg/dl, respectively. A high proportion of the newborns (65.52 %) had cord blood lead levels above the Centers for Disease Control (CDC) allowable threshold limit (3.5 µg/dl). Statistical analysis was performed to assess the association between blood levels and the above factors. Lead levels in cord blood were significantly associated with the maternal educational level, anemia history, delivery mode, passive smoking during pregnancy as well as with the frequency of consumption of tea. CONCLUSION: This study provides the first data on lead levels in newborns. Cord blood lead levels were high in the majority of the participants, these results reinforce the need to establish health surveillance programs in Morocco.

Impact of antenatal exposure to a mixture of persistent organic pollutants on intellectual development.

OBJECTIVE: Strong experimental evidence exists that several endocrine disrupting chemicals (EDCs) have neurobehavioral toxicity. However, evidence of associations between prenatal exposure and child's cognitive development is inconsistent. Moreover, toxicants are generally analyzed one by one without considering aggregate effects. We examined here the impact of a prenatal exposure to a mixture of persistent organic pollutants (POPs) on intellectual abilities in preschool children, and compared their effects to those described in the literature. METHODS: Sixty-two children were included in a longitudinal cohort. Four organochlorine pesticides, four polychlorinated biphenyls (PCBs) and seven perfluorinated compounds (PFCs) were measured in cord blood. Intellectual abilities were assessed at 6 years of age using the Wechsler Preschool and Primary Scale of Intelligence 4th ed. (WPPSI-IV). We examined the associations between a mixture of POPs and cognitive performances using principal components approach (PCA) and weighted quantile sum (WQS) regression taking sex difference into account. RESULTS: No negative correlation was found when analyses were performed on boys and girls together. In sex-stratified analyses, lower scores in full scale intelligence quotient (FSIQ) and fluid reasoning index (FRI) were observed in boys most exposed to a mixture of POPs. Increase of the WQS index was also associated with lower verbal comprehension index (VCI) scores in girls only. No other negative correlation was found using both WQS and PCA models. CONCLUSION: Our study suggests deleterious associations between antenatal exposure to a mixture of POPs and sex-specific cognitive level, clarifying some trends described in the literature.

Assessment of maternal phthalate exposure in urine across three trimesters and at delivery (umbilical cord blood and placenta) and its influence on birth anthropometric measures.

Phthalates, commonly used in plastic manufacturing, have been linked to adverse reproductive effects. Our research from the Saudi Early Autism and Environment Study (2019-2022), involving 672 participants, focused on the impacts of maternal phthalate exposure on birth anthropometric measures. We measured urinary phthalate metabolites in 390 maternal samples collected during each of the three trimesters of pregnancy and in cord serum and placental samples obtained at delivery. We employed various statistical methods to analyze our data. Intraclass correlation coefficients were used to assess the consistency of phthalate measurements, generalized estimating equations were used to explore temporal variations across the trimesters, and linear regression models, adjusted for significant confounders and Bonferroni correction, were used for each birth outcome. Exposure to six phthalates was consistently high across trimesters, with 82 %-100 % of samples containing significant levels of all metabolites, except for mono-benzyl phthalate. We found a 3.15 %-3.73 % reduction in birth weight (BWT), 1.39 %-1.69 % reduction in head circumference (HC), and 3.63 %-5.45 % reduction in placental weight (PWT) associated with a one-unit increase in certain urinary di(2-ethylhexyl) phthalate (DEHP) metabolites during the first trimester. In the second trimester, exposure to MEP, ∑7PAE, and ∑LMW correlated with a 3.15 %-4.5 % increase in the APGAR 5-min score and increases in PWT by 8.98 % for ∑7PAE and 9.09 % for ∑LMW. Our study also highlighted the maternal-to-fetal transfer of DEHP metabolites, indicating diverse impacts on birth outcomes and potential effects on developmental processes. Our study further confirmed the transfer of DEHP metabolites from mothers to fetuses, evidenced by variable rates in the placenta and cord serum, with an inverse relationship suggesting a passive transfer mechanism. Additionally, we observed distinct phthalate profiles across these matrices, adversely impacting birth outcomes. In serum, we noticed increases associated with DEHP metabolites, with birth gestational age rising by 1.01 % to 1.11 %, HC by 2.84 % to 3.67 %, and APGAR 5-min scores by 3.77 % to 3.87 %. Conversely, placental analysis revealed a different impact: BWT decreased by 3.54 % to 4.69 %, HC reductions ranged from 2.57 % to 4.69 %, and chest circumference decreased by 7.13 %. However, the cephalization index increased by 3.67 %-5.87 %. These results highlight the complex effects of phthalates on fetal development, indicating their potential influence on crucial developmental processes like sexual maturation and brain development.

Prenatal exposure to environmental phenols and phthalates and altered patterns of DNA methylation in childhood.

INTRODUCTION: Epigenetic marks are key biomarkers linking the prenatal environment to health and development. However, DNA methylation associations and persistence of marks for prenatal exposure to multiple Endocrine Disrupting Chemicals (EDCs) in human populations have not been examined in great detail. METHODS: We measured Bisphenol-A (BPA), triclosan, benzophenone-3 (BP3), methyl-paraben, propyl-paraben, and butyl-paraben, as well as 11 phthalate metabolites, in two pregnancy urine samples, at approximately 13 and 26 weeks of gestation in participants of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (N = 309). DNA methylation of cord blood at birth and child peripheral blood at ages 9 and 14 years was measured with 450K and EPIC arrays. Robust linear regression was used to identify differentially methylated probes (DMPs), and comb-p was used to identify differentially methylated regions (DMRs) in association with pregnancy-averaged EDC concentrations. Quantile g-computation was used to assess associations of the whole phenol/phthalate mixture with DMPs and DMRs. RESULTS: Prenatal BPA exposure was associated with 1 CpG among males and Parabens were associated with 10 CpGs among females at Bonferroni-level significance in cord blood. Other suggestive DMPs (unadjusted p-value < 1 × 10-6) and several DMRs associated with the individual phenols and whole mixture were also identified. A total of 10 CpG sites at least suggestively associated with BPA, Triclosan, BP3, Parabens, and the whole mixture in cord blood were found to persist into adolescence in peripheral blood. CONCLUSIONS: We found sex-specific associations between prenatal phenol exposure and DNA methylation, particularly with BPA in males and Parabens in females. Additionally, we found several DMPs that maintained significant associations with prenatal EDC exposures at age 9 and age 14 years.

Arachidonic acid-derived dihydroxy fatty acids in neonatal cord blood relate symptoms of autism spectrum disorders and social adaptive functioning: Hamamatsu Birth Cohort for Mothers and Children (HBC Study).

AIM: Autism spectrum disorder (ASD) is associated with abnormal lipid metabolism, such as a high total ratio of omega-6 to omega-3 in polyunsaturated fatty acids (PUFAs). PUFAs are metabolized to epoxy fatty acids by cytochrome P450 (CYP); then, dihydroxy fatty acid is produced by soluble epoxide hydrolase. This study examined the association between PUFA metabolites in the cord blood and ASD symptoms and adaptive functioning in children. METHODS: This prospective cohort study utilized cord blood to quantify PUFA metabolites of the CYP pathway. The Autism Diagnostic Observation Schedule (ADOS-2) and Vineland Adaptive Behaviors Scales, Second Edition (VABS-II) were used to assess subsequent ASD symptoms and adaptive functioning in children at 6 years. The analysis included 200 children and their mothers. RESULTS: Arachidonic acid-derived diols, 11,12-diHETrE was found to impact ASD symptom severity on the ADOS-2-calibrated severity scores and impairment in the socialization domain as assessed by the VABS-II (P = 0.0003; P = 0.004, respectively). High levels of 11,12-diHETrE impact social affect in ASD symptoms (P = 0.002), while low levels of 8,9-diHETrE impact repetitive/restrictive behavior (P = 0.003). Notably, there was specificity in the association between diHETrE and ASD symptoms, especially in girls. CONCLUSION: These findings suggest that the dynamics of diHETrE during the fetal period is important in the developmental trajectory of children after birth. Given that the role of diol metabolites in neurodevelopment in vivo is completely uncharacterized, the results of this study provide important insight into the role of diHETrE and ASD pathophysiology.

Association Between Dietary Phytochemical Index and Neonatal Thyroid Function.

Background: Thyroid hormones regulate fetal growth and differentiation of several tissues. Maternal dietary patterns may be correlated with changes in the level of neonatal thyroid-stimulating hormone (TSH). We hypothesized that since maternal nutrition affects birth weight and offspring growth, it may also impact endocrine patterns in offspring. This study is aimed at assessing the relationship between maternal dietary phytochemical index (DPI) in the first trimester of pregnancy and neonatal cord blood thyroid hormone levels. Methods: This cross-sectional study is a substudy of a birth cohort. Overall, 216 mothers, aged 16-45 years, were recruited in their first trimester of pregnancy. To calculate DPI, the daily energy percentage of phytochemical-rich foods was divided by the total daily energy intake. At delivery time, TSH and free thyroxine (FT4) levels were measured in cord blood samples using chemiluminescence immunoassay. Results: The mean (standard deviation (SD)) age of mothers was 29.56 (5.50) years, and 47% of newborns were girls. The mean (SD) of DPI in the first, second, third, and fourth quartiles was 25.03 ± 4.67, 33.87 ± 2.18, 40.64 ± 2.10, and 51.17 ± 4.98, respectively. There was not any significant correlation between DPI score with cord serum TSH and FT4 levels in crude and adjusted analysis. Conclusion: No significant relationship between maternal DPI with cord serum TSH and FT4 levels was shown. Limited experience exists about the effect of maternal diet quality indices on neonatal thyroid function, and further studies are needed in this regard.