Early Pregnancy Serum Research Articles

Early pregnancy serum PFAS are associated with alterations in the maternal lipidome

Per- and polyfluoroalkyl substances (PFAS) have been detected in the blood of humans and animals worldwide. Exposure to some PFAS are associated with multiple adverse pregnancy outcomes. Existing literature has identified a strong association with PFAS exposure and metabolic dysfunction in humans, including modification of lipid metabolism. Using a subset of the Michigan Mother-Infant Pairs cohort (n=95), this study investigated associations between first trimester plasma levels of PFAS and maternal lipids and metabolites in the first trimester (T1), at the time of delivery (T3), and in the infant cord blood (CB) using untargeted shotgun lipidomics and metabolomics. Identifying PFAS-induced alterations in the maternal lipid- or metabolome at specific timepoints may help elucidate windows of susceptibility to adverse pregnancy outcomes. Out of 9 PFAS measured, 7 were detected in at least 20% of samples and were used for further analyses. PFOS and PFHxS were measured at the highest concentrations with medians of 5.76 ng/ml and 3.33 ng/ml, respectively. PFOA, PFNA, and PFDA had lower measured values with medians of < 1.2 ng/mL. PFHxS concentrations were positively associated with monounsaturated sphingomyelins (SMs) in T1 maternal plasma in adjusted models, determined by an adjusted p-value (q) < 0.1. PFHxS was positively associated with saturated and polyunsaturated SMs and inversely associated with saturated diacylglycerols in T1. Following metabolite-specific analysis, two mono-unsaturated diacylglycerols with carbon chain lengths of 32 and 35 were inversely associated with PFHxS in T1. In T3, only the association between PFHxS and SMs remained, but was attenuated. In addition, PFDA was associated with an increase in polyunsaturated plasmenyl-phosphatidylethanolamines in T3. No associations were identified between PFAS and infant cord blood lipids. Continued research into PFAS associated disruptions in lipid metabolism at sensitive stages of gestation may provide insight into the mechanisms that lead to adverse birth and pregnancy outcomes.

Alteration of Maternal Serum Ferritin in Pregnancy and Maternal-fetal Infections: A retrospective cohort study.

To investigate the association of altered serum ferritin during pregnancy with chorioamnionitis and neonatal sepsis. This retrospective cohort study included 78,521 pregnant women who attended antenatal check-ups at maternal and child health centers in Fujian Province, China. Study lasted from January 2014 to January 2019. A total of 59,812 pregnant women were followed up. Patients with suspected infection before the delivery were selected and divided into the chorioamnionitis and non-chorioamnionitis groups according to placental pathology. Differences in late and early pregnancy serum ferritin between the two groups were compared. Multiple logistics regression was used to adjust for confounding factors and to analyze the association between serum ferritin changes and pregnancy outcomes. Importance of altered serum ferritin during pregnancy was assessed by receiver operating characteristic (ROC) curve and net reclassification index (NRI). Clinical records of 8506 pregnant women were included in the study. there were 1010 (11.9%) cases of confirmed chorioamnionitis and 263 (3.1%) cases of neonatal sepsis. There was a significant difference in maternal serum ferritin changes between the groups with and without chorioamnionitis. No significant difference was detected in cases with or without neonatal sepsis. Multiple logistic regressions, corrected for confounding factors yielded similar conclusions. Maternal serum ferritin difference NRI 12.18% (p = 0.00014) was similar to the ROC results in predicting the occurrence of chorioamnionitis. Differential serum ferritin during pregnancy may predict chorioamnionitis but does not correlate well with neonatal sepsis.

Trophectoderm grade as a predictor of beta human-chorionic gonadotropin rise in early pregnancy.

To evaluate the association, if any, between the grade of the trophectoderm (TE) and the rate at which β-human-chorionic gonadotropin (β-HCG) rises in early pregnancy. This is a retrospective cohort study including 1116 singleton clinical pregnancies resulting from in vitro fertilization with single day 5 blastocyst transfer at an academic fertility center. TE quality was assessed by trained embryologists employing standard criteria. Three groups were formed based on the TE grade: grade A (n = 358), grade B (n = 628), and grade C (n = 130). Main outcome measure was the rise (%) in serum levels of β-HCG (days 12 to 14 post embryo transfer), using the following formula [(β-HCG D14 - β-HCG D12) * 100/β-HCG D12]. Fresh embryo transfers accounted for 64.1% of the population. Overall, in adjusted models there were no significant differences in the β-HCG% rise when comparing the TE grade C group to TE grade A [adjβ (95%CI): 10.09 (- 0.05, 20.22)] or when comparing TE grade Β group to TE grade A [4.46 (- 2.97, 11.88)]. When the analysis was restricted to fresh embryo transfers, significant differences were observed in the % rise of β-HCG when comparing the TE grade C group to TE grade A [adjβ (95%CI): 21.71 (5.67, 37.74)], but not when comparing the TE grade B group to TE grade A [2.68 (- 5.59, 10.95)]. In frozen transfers, there were no significant differences. TE grade appears to impact early pregnancy serum β-HCG levels in the setting of a fresh day 5 embryo transfer, even after adjusting for potential confounders.

Association between prenatal exposure to alkylphenols and intelligence quotient among preschool children: sex-specific effects

BackgroundWhile prenatal exposure to alkylphenols (APs) has been demonstrated to be associated with neurodevelopmental impairments in animals, the evidence from epidemiological studies remains limited and inconclusive. This study aimed to explore the link between AP exposure during pregnancy and the intelligence quotient (IQ) of preschool children.MethodsA total of 221 mother-child pairs from the Guangxi Zhuang Birth Cohort were recruited. Nonylphenol (NP), 4-tert-octylphenol (4-T-OP), 4-n-nonylphenol (4-N-NP), and 4-n-octylphenol were measured in maternal serum in early pregnancy. Childhood IQ was evaluated by the Fourth Edition of Wechsler Preschool and Primary Scale of the Intelligence at 3 to 6 years of age. The impact of APs on childhood IQ were evaluated by generalized linear models (GLMs), restricted cubic spline (RCS), and Bayesian kernel machine regression (BKMR).ResultsIn GLMs, prenatal exposure to NP and the second tertile of 4-T-OP exhibited an inverse association with full-scale IQ (FSIQ) (β = -2.38; 95% CI: -4.59, -0.16) and working memory index (WMI) (β = -5.24; 95% CI: -9.58, -0.89), respectively. Prenatal exposure to the third tertile of 4-N-NP showed a positive association with the fluid reasoning index (β = 4.95; 95% CI: 1.14, 8.77) in total children, as well as in girls when stratified by sex. A U-shaped relationship between maternal 4-T-OP and WMI was noted in total children and girls by RCS (all P nonlinear < 0.05). The combined effect primarily driven by NP, of maternal AP mixtures at concentrations above the 50th percentile exhibited an inverse trend on FSIQ in total children and girls in BKMR.ConclusionsPrenatal exposure to various APs affects IQ in preschool children, and there may be nonmonotonic and sex-specific effects. Further investigation across the population is required to elucidate the potential neurotoxic effects of APs.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study

BackgroundPrevious evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women.MethodsThe study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records.ResultsThe mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001–0.028).ConclusionHigher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Investigation of cytokines in equine serum, conceptuses and endometrium in early pregnancy

Cytokines and their receptor systems are present at the fetomaternal interface of some species and regulate trophoblast biology. The cytokine and chemokine systems are key in the communication between fetal derived trophoblast cells and the maternal tissue. However, evidence for the presence of cytokines and their receptors during early equine pregnancy is lacking. Our objective was to investigate interleukins, chemokine ligands, dendritic cells and TNFα in equine serum, conceptuses and endometrium during early pregnancy. Daily transrectal ultrasound examinations of the mares were performed when in estrus until the day (D) of ovulation (OV). An endometrial biopsy was taken from non-pregnant (NP) mares at: D11 (NP11; n=6) or D13 (NP13; n=7). Mares in the pregnant (P) group were bred by artificial insemination from a single fertile stallion, and transrectal ultrasound was performed to detect and measure conceptuses. On the day of sample collection, conceptuses were collected through a transcervical bivona catheter and uterine lavage using 0.9% NaCl, and this was followed by an endometrial biopsy. Pregnant mares’ conceptuses and endometrial biopsies were retrieved at D11 (P11; n=7), D13 (P13; n=8), or D16 (P16; n=6). A D16 sample was not obtained for NP group. A Bradford assay was performed on extracted endometrium and conceptus tissue to determine total protein concentration,followed by a bead-based equine validated multiplex assay (Luminex Corp. Austin, TX) to quantify concentration of the following equine specific inflammatory markers: IL-4, IL-17, IL-10, IL-1β, CCL2, CCL3, CCL5, CCL11, sCD-14 and TNFα. A restricted maximum likelihood model was performed to compare the protein concentration between groups and days in JMP Pro 16 (Cary, NC) with the mare as a random factor and significance set at p<0.05. Cytokine and chemokine serum concentrations were similar between groups and days of collection. Regarding the endometrium, IL-17 U/mg was higher (p<0.05) in group NP13 [median (interquartile)] [11.4 (8.2, 21.7)] than NP11 [4.1 (2.6, 5.3)]. In pregnant mares, endometrial IL-17 was higher in P13 group [6.3 (3.4, 13.9)] compared to group P16 [2.5 (2.1, 4.8)] (p<0.05). In conceptuses, D11 had significantly higher concentrations of CCL2 [1350.2 (793, 1839.5); p<0.03], CCL3 [1990.9 (998.6, 3083.8); p<0.01], CCL5 [363.2 (149.6, 480.6); p<0.006] and CCL11[3143.7 (1764.2, 5221.9); p<0.01 compared to D16 [66.7 (38.8, 644.8); 67.8 (43, 572.30); 9.1 (6.6, 96.3); 196.2 (150.9, 1436.6)], respectively. Higher chemokine concentrations in the earlier embryos may reflect the recruitment of endometrial leukocytes. Further investigation into the role of cytokines and chemokines in early equine pregnancy is warranted.

The effect of thyroid autoimmunity on early pregnancy serum ß-hCG levels in spontaneous pregnancy

Aims: To examine the association between thyroid autoimmunity (TAI) and early pregnancy serum beta human chorionic gonadotropin (ß-hCG) levels in spontaneous pregnancy. Methods: In this retrospective case-control study, women between the ages of 20 and 40 were included. The study subjects were 130 women euthyroid and healthy patients with spontaneous pregnancy. Subjects were divided into two groups: those with autoimmune thyroid disease (TAI group; n=60) and those without the disease (control group; n=70). Results: The mean age and body mass index (BMI) of the subjects were 30.22±4.14 years and 24.51±2.04, respectively. The value of anti-thyroid peroxidase antibodies (TPO-Abs) and anti-thyroglobulin antibodies (TG-Abs) in the TAI group is three times twenty times more than the control, respectively. Results found no statistically significant association between between TAI and control groups in regard to hemoglobin, alanine transaminase (ALT), aspartate transaminase (AST), thyroid-stimulating hormone (TSH), platelet (PLT), creatine, free thyroxin (FT4), and blood urea nitrogen (BUN) (p&gt;0.05). There was statistically significant difference between groups in terms of the serum ß-hCG level (p&lt;0.05). Conclusion: In this study, the effects of TAI were significant on early-stage pregnancy serum ß-hCG levels; therefore, thyroid levels should be considered, and proper treatment should be started early.

Aberrations in the early pregnancy serum metabolic profile in women with prediabetes at two years postpartum

IntroductionAberrations in circulating metabolites have been associated with diabetes and cardiovascular risk.ObjectivesTo investigate if early and late pregnancy serum metabolomic profiles differ in women who develop prediabetes by two years postpartum compared to those who remain normoglycemic.MethodsAn NMR metabolomics platform was used to measure 228 serum metabolite variables from women with pre-pregnancy overweight in early and late pregnancy. Co-abundant groups of metabolites were compared between the women who were (n = 40) or were not (n = 138) prediabetic at two years postpartum. Random Forests classifiers, based on the metabolic profiles, were used to predict the prediabetes status, and correlations of the metabolites to glycemic traits (fasting glucose and insulin, HOMA2-IR and HbA1c) and hsCRP at postpartum were evaluated.ResultsWomen with prediabetes had higher concentrations of small HDL particles, total lipids in small HDL, phospholipids in small HDL and free cholesterol in small HDL in early pregnancy (p = 0.029; adj with pre-pregnancy BMI p = 0.094). The small HDL related metabolites also correlated positively with markers of insulin resistance at postpartum. Similar associations were not detected for metabolites in late pregnancy. A Random Forests classifier based on serum metabolites and clinical variables in early pregnancy displayed an acceptable predictive power for the prediabetes status at postpartum (AUROC 0.668).ConclusionElevated serum concentrations of small HDL particles in early pregnancy associate with prediabetes and insulin resistance at two years postpartum. The serum metabolic profile during pregnancy might be used to identify women at increased risk for type 2 diabetes.

Association between maternal exposure to per- and polyfluoroalkyl substances and serum markers of liver function during pregnancy in China: A mixture-based approach

Previous studies have shown that per- and polyfluoroalkyl substances (PFAS) may have hepatotoxic effects in animals. However, epidemiological evidence in humans, especially pregnant women, is limited. This study aimed to assess the association of single and multiple PFAS exposure with serum markers of liver function in pregnant women. A total of 420 pregnant women from the Guangxi Zhuang Birth Cohort were enrolled from June 2015 to April 2019. Nine PFAS were measured in the maternal serum in early pregnancy. Data for liver function biomarkers, namely, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL), were obtained from medical records. In generalized linear model (GLM), there was a positive association of perfluorooctane sulfonate (PFOS) with ALT, perfluorodecanoic acid (PFDA) and perfluorobutanesulfonic acid (PFBS) with GGT, and perfluorohexane sulfonate (PFHxS) with TBIL and IBIL. In contrast, there was a negative association of perfluoroheptanoic acid (PFHpA) with TBIL. There were inverse U-shaped relationships of PFUnA with ALT and AST and PFDA with ALT by restricted cubic spline. The weighted quantile sum (WQS) regression model revealed the positive effects of the PFAS mixture on GGT, TBIL, DBIL, and IBIL. Bayesian kernel machine regression (BKMR) analysis confirmed that the PFAS mixture was positively associated with GGT, and PFBS was the main contributor. In addition, the BKMR model showed a positive association of individual PFBS with GGT, individual PFHxS with TBIL and IBIL, and a negative association of individual PFHpA with TBIL. Our findings provide evidence of an association between individual PFAS, PFAS mixture and maternal serum markers of liver function during pregnancy. Additionally, these findings also enhance concerns over PFAS exposure on maternal liver function and PFAS monitoring in pregnancy, reducing the effect of maternal liver dysfunction on maternal and infant health.

Early Pregnancy Serum Ferritin in the Non-Anemic Patient as a Predictor of Anemia at Delivery

Early Pregnancy Serum Ferritin in the Non-Anemic Patient as a Predictor of Anemia at Delivery

African American Women with Cardiometabolic Complications of Pregnancy Have Decreased Serum Abundance of Specialized Pro-Resolving Lipid Mediators and Endocannabinoids.

African American (AA) women experience higher rates of maternal morbidity and mortality compared to US women of other racial/ ethnic groups. Cardiometabolic complications of pregnancy (including gestational diabetes, gestational hypertension, and preeclampsia) are leading contributors to maternal morbidity and mortality. Marked changes in circulating lipids are known to accompany cardiometabolic complications of pregnancy. Serum concentrations of docosahexaenoic acid (DHA) have been shown to be inversely correlated with risk for preeclampsia. DHA is a biosynthetic precursor of a class of specialized pro-resolving mediators (SPMs), resolvins, that have anti-inflammatory properties and are also associated with hypertensive disorders of pregnancy. We employed targeted lipidomics to characterize the distribution of DHA-containing phospholipids and SPMs in maternal serum collected in early and late pregnancy (8-14 weeks and 24-30 weeks gestation, respectively) to identify key lipids that are dysregulated during pregnancy in AA women who develop cardiometabolic complications. We identified a lipid signature in early pregnancy serum samples of AA women that is predictive of cardiometabolic complications of pregnancy with 74% accuracy. These are Resolvin D1, Resolvin E1, 2-AG, PGE2-glyerol ester, and 36:6 PC. These findings suggest that there are blood-based markers detectable in early pregnancy that can potentially identify persons at risk and tailor clinical interventions.

Associations of Early Pregnancy Metabolite Profiles with Gestational Blood Pressure Development.

Blood pressure development plays a major role in both the etiology and prediction of gestational hypertensive disorders. Metabolomics might serve as a tool to identify underlying metabolic mechanisms in the etiology of hypertension in pregnancy and lead to the identification of novel metabolites useful for the prediction of gestational hypertensive disorders. In a population-based, prospective cohort study among 803 pregnant women, liquid chromatography—mass spectrometry was used to determine serum concentrations of amino-acids, non-esterified fatty acids, phospholipids and carnitines in early pregnancy. Blood pressure was measured in each trimester of pregnancy. Information on gestational hypertensive disorders was obtained from medical records. Higher individual metabolite concentrations of the diacyl-phosphatidylcholines and acyl-lysophosphatidylcholines group were associated with higher systolic blood pressure throughout pregnancy (Federal Discovery Rate (FDR)-adjusted p-values < 0.05). Higher concentrations of one non-esterified fatty acid were associated with higher diastolic blood pressure throughout pregnancy (FDR-adjusted p-value < 0.05). Using penalized regression, we identified 12 individual early-pregnancy amino-acids, non-esterified fatty acids, diacyl-phosphatidylcholines and acyl-carnitines and the glutamine/glutamic acid ratio, that were jointly associated with larger changes in systolic and diastolic blood pressure from first to third trimester. These metabolites did not improve the prediction of gestational hypertensive disorders in addition to clinical markers. In conclusion, altered early pregnancy serum metabolite profiles mainly characterized by changes in non-esterified fatty acids and phospholipids metabolites are associated with higher gestational blood pressure throughout pregnancy within the physiological ranges. These findings are important from an etiological perspective and, after further replication, might improve the early identification of women at increased risk of gestational hypertensive disorders.

Early pregnancy serum levels of folate and vitamin B12 in overweight and obese women in Khartoum, Sudan.

This study was conducted to assess serum levels of folate and vitamin B12 in overweight and obese pregnant women. A cross-sectional study was conducted at Saad Abualila Hospital, Sudan. Clinical data were collected through questionnaires and body mass index (BMI) was computed from weight and height. The serum folate and vitamin B12 levels were analyzed by immunofluorescence. Of 300 enrolled women, 44.7% were of normal weight, 32.3% were overweight and 3.0% were obese. The folate level was significantly lower in overweight women (median 4.79 ng/ml [IQR 2.70‒7.70]) than in normal-weight women (median 6.650 ng/ml [IQR 3.30‒10.55]; p=0.022). There was no significant difference in the prevalence of marginal and severe folate deficiencies in women in different BMI groups. Compared with normal-weight women (median 197.5 pg/ml [IQR 150.0‒263.0]), obese women (median 173.0 pg/ml [IQR 150.0‒213.0]; p=0.038) had significantly lower vitamin B12 levels and had a higher prevalence of vitamin B12 insufficiency. Fair negative correlations (p<0.01) were observed between folate and BMI (r = -0.157) and between vitamin B12 and BMI (r = -0.173). Overweight and obese pregnant Sudanese women had lower levels of serum folate and vitamin B12.

Vitamin D status in pregnancy and childhood associates with intelligence quotient at age 7 years: An Odense child cohort study.

Animal studies indicate a key role for vitamin D in brain development and function, but observational studies in humans only suggests a borderline positive association between prenatal vitamin D exposure and cognitive development in the offspring. Knowledge gaps include insights in exposure time window and differences by sex for the association. We aimed to investigate the association between blood concentrations of serum 25-hydroxyvitamin D measured at four different time points and intelligence quotient score at the age of 7 years, including analyses spilt by child sex. In Odense child cohort, we included 1404 mother-child pairs with serum 25-hydroxyvitamin D data from early pregnancy to age 7 years. Full-scale intelligence quotient was assessed with Wechsler Intelligence Scale for Children - fifth edition. Associations were adjusted for maternal education, pre-pregnancy body mass index, gestational age, sex and head circumference. Subanalyses stratified by sex were performed. The median (interquartile range) serum 25-hydroxyvitamin D in cord was 45.88 (31.15-61.08) nmol/L; early pregnancy, 66.45 (51.29-78.74); late pregnancy, 79.13 (59.69-97.31); 7 years, 66.29 (53.45-80.23) nmol/L. The mean (standard deviation) full-scale intelligence quotient was 99.44 (11.98). In adjusted analyses, cord serum 25-hydroxyvitamin D < 50 nmol/L was associated with 2.2 points lower full-scale intelligence quotient compared to the reference (50-75 nmol/L) in boys, β = -2.2; 95% confidence interval = [-4.3, -0.1], p = 0.039. The same association with full-scale intelligence quotient was found for early pregnancy serum 25-hydroxyvitamin D, β = -2.5 [-4.6, -0.3], p = 0.025, primarily driven by an association in boys, β = -4.0 [-7.2, -0.8], p = 0.015; and for serum 25-hydroxyvitamin D at 7 years in girls, β = -3.0 [-6.0, -0.1], p = 0.042. In this cohort, serum 25-hydroxyvitamin D < 50 nmol/L in both early gestation and cord blood in boys and current serum 25-hydroxyvitamin D < 50 nmol/L in girls were independent risk factors for two to four points lower full-scale intelligence quotient at the age of 7 years. Vulnerability to hypovitaminosis D, especially in pregnancy, may relate to child sex.

Atopic heredity modifies the association between maternal vitamin D status in pregnancy and the risk of atopic disease in childhood: an observational study

BackgroundThe relationship between maternal vitamin D status in pregnancy and the development of atopic diseases in the offspring has been frequently studied, but with contradictory results. Previous studies have found an inverse relation between maternal vitamin D in pregnancy and the risk of atopic diseases in the child. In contrast, others have found a higher maternal 25OHD to be related to a higher risk of atopic diseases. Thus, the aim was to investigate the associations between maternal vitamin D status and intake in pregnancy with asthma, eczema and food allergies in the children up to 5 years. In addition, effect modification by reported atopic heredity was studied.MethodsParticipants in the GraviD study had 25-hydroxyvitamin D (25OHD) analyzed in serum in early (T1) and late (T3) pregnancy. Maternal dietary vitamin D intake was estimated from a short food frequency questionnaire and supplement use by questionnaires. At 5 years of age the child´s history of asthma, eczema and food allergy, including atopic heredity, was reported by questionnaire. Multivariable logistic regression was used.ResultsThe cumulative incidence of asthma was 13%, eczema 22%, and food allergy 18%. Only among children without reported atopic heredity, maternal 25OHD of 50–75 nmol/L in T1 was associated with lower odds of asthma (OR 0.271, 95% CI 0.127–0.580), compared to maternal 25OHD > 75 nmol/L. Additionally in these children, maternal 25OHD in T3 (continuous) was associated with asthma (OR 1.014, 95% CI 1.002–1.009), and dietary vitamin D intake with eczema (OR 1.141, 95% CI 1.011–1.288).ConclusionsAmong children without reported atopic heredity, higher maternal vitamin D status and intake during pregnancy was associated with increased risk of reported atopic disease.

Maternal iron status in early pregnancy and DNA methylation in offspring: an epigenome-wide meta-analysis

BackgroundUnbalanced iron homeostasis in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism linking environmental exposures such as micronutrient status during pregnancy with offspring health. We performed a meta-analysis on the association of maternal early-pregnancy serum ferritin concentrations, as a marker of body iron stores, and cord blood DNA methylation. We included 1286 mother–newborn pairs from two population-based prospective cohorts. Serum ferritin concentrations were measured in early pregnancy. DNA methylation was measured with the Infinium HumanMethylation450 BeadChip (Illumina). We examined epigenome-wide associations of maternal early-pregnancy serum ferritin and cord blood DNA methylation using robust linear regression analyses, with adjustment for confounders and performed fixed-effects meta-analyses. We additionally examined whether associations of any CpGs identified in cord blood persisted in the peripheral blood of older children and explored associations with other markers of maternal iron status. We also examined whether similar findings were present in the association of cord blood serum ferritin concentrations with cord blood DNA methylation.ResultsMaternal early-pregnancy serum ferritin concentrations were inversely associated with DNA methylation at two CpGs (cg02806645 and cg06322988) in PRR23A and one CpG (cg04468817) in PRSS22. Associations at two of these CpG sites persisted at each of the follow-up time points in childhood. Cord blood serum ferritin concentrations were not associated with cord blood DNA methylation levels at the three identified CpGs.ConclusionMaternal early-pregnancy serum ferritin concentrations were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.

Early Pregnancy Serum Concentration of Secreted Frizzled-Related Protein 4, Secreted Frizzled-Related Protein 5, and Chemerin in Obese Women Who Develop Gestational Diabetes Mellitus

Background: The aim of this study was to evaluate whether secreted frizzled-related protein 4 (sFRP4), secreted frizzled-related protein 5 (sFRP5), and chemerin serum concentrations in early pregnancy are associated with the development of gestational diabetes mellitus (GDM) in an obese cohort. In previous studies, increased sFRP4 and chemerin, and decreased sFRP5 concentrations were associated with the development of GDM in normal and overweight women. Methods: In this exploratory case control study, sFRP4, sFRP5, and chemerin serum concentrations were determined by ELISA in 50 obese women who developed GDM and 100 uncomplicated control pregnancies. Serum samples were obtained between 15+0–18+6 weeks’ gestational age and based on a priori known associations with the development of GDM, body mass index (BMI) and maternal age were selected for adjustment in multivariate analyses. Results: In this obese cohort (median BMI 35.7 kg/m2, IQR 33.2–40.3 kg/m2), the biochemical markers showed no association with GDM: sFRP5 odds ratio (OR) 0.44 (95% confidence interval (CI) 0.01–23.18, p = 0.687), sFRP4 OR 0.55 (95% CI 0.09–3.52, p = 0.528), and chemerin OR 3.47 (95% CI 0.05–227.72, p = 0.560). Adjustment for BMI and maternal age did not influence the association. None of the markers were significantly correlated with insulin resistance (HOMA2-IR). Conclusion: No association was found between sFRP4, sFRP5, or chemerin concentration and the development of GDM in a cohort of obese pregnant women. The absence of the association may indicate that these proteins play a lesser biological role in the pathophysiology of GDM in obese women.

Year-end academic review of 2021: Advances in the field of birth defect prevention and control in China as of 2021

Year-end academic review of 2021: Advances in the field of birth defect prevention and control in China as of 2021

Maternal Iron Status in Early Pregnancy and Blood Pressure Throughout Pregnancy, Placental Hemodynamics, and the Risk of Gestational Hypertensive Disorders

BackgroundIn nonpregnant populations, higher serum ferritin, which reflects high iron stores, is associated with an increased risk of hypertension. We hypothesized that a dysregulated maternal iron status in early pregnancy may lead to impaired gestational hemodynamic adaptations, leading to an increased risk of gestational hypertensive disorders. ObjectivesWe examined the associations of maternal iron status with maternal blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders. MethodsIn a population-based prospective cohort study among 5983 pregnant women, we measured maternal serum ferritin, transferrin saturation, serum iron, and transferrin concentrations at a median of 13.2 weeks gestation (95% range, 9.6–17.6). Maternal blood pressure was measured in early pregnancy, mid pregnancy, and late pregnancy, and placental hemodynamic parameters in mid pregnancy and late pregnancy were measured by ultrasound. Information on gestational hypertensive disorders was collected from medical records. We examined the associations of maternal early pregnancy iron status with maternal systolic and diastolic blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders using linear and logistic regression models. ResultsHigher maternal early pregnancy serum ferritin concentrations were associated with higher systolic and diastolic blood pressure throughout pregnancy in the basic models (P values < 0.05). After adjustment for maternal inflammation, sociodemographic and lifestyle factors, higher maternal early pregnancy serum ferritin concentrations were only associated with a higher early pregnancy diastolic blood pressure [0.27 (95% CI, 0.03–0.51) mmHg per SD score increase in serum ferritin] and with a higher mid pregnancy umbilical artery pulsatility index (P < 0.05). No associations with the risk of gestational hypertensive disorders were present. ConclusionsNo consistent associations were present of maternal iron status in early pregnancy with gestational hemodynamic adaptations or the risks of gestational hypertensive disorders. Further studies are needed to examine the potential role of iron metabolism in the development of gestational hypertensive disorders within higher-risk populations.

Meta-analysis and randomized controlled studies: what clinicists should know to prevent regular and spontaneous miscarriages of unexplained genesis?

The etiopathology of recurrent miscarriage is a combination of various factors, including chromosomal defects, genetic or structural abnormalities, endocrine abnormalities, infections, immune dysfunction, thrombophilia disorders, antiphospholipid syndrome, and unexplained causes.It has long been known that progesterone is needed to maintain pregnancy and its physiological development. Insufficient progesterone secretion and its low level in the blood serum in early pregnancy is associated with the threat of miscarriage and loss of pregnancy at a later stage – up to 16 weeks of gestation. The effectiveness of the vaginal micronized progesterone (VMP) at a dose of 400 mg twice a day in the first trimester of pregnancy was evaluated in two recent large high-quality multicenter placebo-controlled studies, one of which included pregnant women with recurrent miscarriages of unexplained origin (PROMISE Trial), and the other study included women with early pregnancy loss (PRISM Trial). A key finding, pioneered in the PROMISE study and later confirmed in the PRISM study, was that VMP treatment associated with an increase in live births in line with the number of previous miscarriages. It has been shown that there is no evidence regarding safety concerns with natural micronized progesterone. Treatment with an VMP should be recommended for women with bleeding in early pregnancy and a history of one or more miscarriages. The recommended treatment regimen is 400 mg 2 times a day (800 mg/day) intravaginal, starting from the moment bleeding is detected up to 16 weeks of pregnancy.In the future, there remains uncertainty effectiveness and safety of alternative progestogens (dydrogesterone) for the treatment of women at high risk of threatened abortion and recurrent miscarriage. It is important that dydrogesterone is a synthetic progestin, its structure is significantly different from natural progesterone, and therefore it is necessary to unequivocally prove the short- and long-term safety of this drug before considering its use in clinical practice.