Maternal Blood Research Articles

Correlation between Maternal Systemic Inflammatory Indicators before Delivery and Congenital Pneumonia in Newborns: A Case-Control Study.

Congenital pneumonia is a common respiratory disease in newborns, often influenced by obstetric factors. Clinical diagnosis can be delayed, prompting interest in using systemic inflammatory indicators to predict various diseases. Our aim was to evaluate the predictive value of maternal systemic inflammatory indicators before delivery for congenital pneumonia in newborns. This retrospective study included full-term, singleton infants born at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University between January 2017 and December 2022. Infants admitted to the neonatal department within 48 h of birth were divided into two groups: 46 with clinical congenital pneumonia (the observation group) and 65 without congenital pneumonia (the control group). Maternal peripheral blood, complete blood cell count, and general condition within 72 h before delivery, as well as neonatal admission data were recorded. Systemic inflammatory indicators were assessed. Receiver operating characteristic curves were used to evaluate the predictive value of the maternal systemic inflammatory indicators before delivery for congenital pneumonia. A prediction model for neonatal pneumonia was constructed by combining systemic inflammatory indicators before delivery with logistic regression. The association between this prediction model and the prognosis of neonatal congenital pneumonia was examined. Maternal systemic inflammatory indicators before delivery as predictive markers for congenital pneumonia and the regression model jointly constructed by NLR, MLR, SII, SIRI, and PIV before delivery predicted the occurrence of congenital pneumonia better. Maternal systemic inflammatory indicators correlated with the severity of congenital pneumonia in neonates. Maternal systemic inflammatory indicators before delivery have predictive value for congenital pneumonia in neonates, aiding early identification and treatment.

Interleukin-6 (-174G/C), Interleukin-1β (-511 C/T), and Apolipoprotein B-100 (2488 C/T) Gene Polymorphism in Pre-Eclampsia.

Background and objectives: Pre-eclampsia (PE) is a pregnancy-specific condition characterized by significant health risks for pregnant women worldwide due to its status as a multi-organ disorder. High blood pressure (hypertension) with or without proteinuria is usually considered an initial clinical sign of PE. The pathogenesis of pre-eclampsia is highly complex and likely involves multiple factors, including poorly developed uterine spiral arterioles, immunological issues, placental ischemia or infarction, and genetic abnormalities. Inflammatory cytokine production, regulated by cytokine gene polymorphisms, is one of the factors likely contributing to the development of PE. The present study aimed to assess IL-6, IL-1β, and Apo B-100 gene polymorphism and to evaluate the association of these polymorphisms with PE. Materials and Methods: This cross-sectional observational study involved 99 participants aged 16 to 45 years from Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan. The participants were divided into three groups: Group 1 (PE with severe hypertension), Group 2 (PE with hypertension), and Group 3 (control), each comprising 33 individuals. Maternal blood samples were collected, DNA was extracted, and molecular genetic analysis of the IL-6, IL-1β, and Apo B-100 genes was performed using the PCR-RFLP method. Allelic frequencies were compared, and statistical analysis was conducted using SPSS 25, applying the Hardy-Weinberg equation and chi-square test to evaluate the results. Results: There are differences in the distribution of allelic frequencies for IL-6 -174G/C (CC, GC, GG), IL-1β-511C/T (CC, CT, TT), and Apo B-100 2488 C/T (CC, CT, TT) between pre-eclamptic patients and the control group. The analysis using the Hardy-Weinberg equilibrium and chi-square test showed an association between the IL-6-174 G/C polymorphism and the severity of pre-eclampsia. Conclusions: The polymorphisms of the IL-6, IL-1β, and Apo B-100 genes revealed different alleles. The IL-6 gene alone was found to be in disequilibrium according to the Hardy-Weinberg equation, indicating a potential link to the severity of pre-eclampsia in the population studied.

Fetal behavior and gestational serotonin reuptake inhibitor exposure: relationships between behavior, drug dosage, plasma drug level, and a measure of drug bioeffect

Determination of the relationships between drug dosage, maternal and infant (cord blood) plasma drug concentrations, and serotonin reuptake inhibitor (SRI) bioeffect on offspring neurobehavior is crucial to assessing the effects of gestational SRI exposure. Measurement of maternal and cord blood platelet serotonin (5-HT) provides an index of inhibitory bioeffect at the 5-HT transporter and complements other measures of drug exposure. Three groups of mother-infant pairs were evaluated: (1) mothers with depression untreated with SRIs (DEP, n = 17), (2) mothers treated for depression with SRIs (DEP + SRI, n = 17), and (3) mothers who were not depressed and untreated (ND, n = 29). Fetal movement was assessed using a standardized ultrasound imaging and rating protocol. Maternal and cord blood platelet 5-HT levels were obtained from all participants. For the SRI + DEP group, maternal and infant plasma drug concentrations and an estimate of third-trimester maternal SRI drug exposure were obtained. As expected, substantially lower median platelet 5-HT levels were observed in the DEP + SRI group than in the non-exposed, combined ND and DEP groups. In non-exposed mothers and infants, platelet 5-HT levels were not affected by the presence of maternal depression. Lower maternal and infant platelet 5-HT levels were associated with more immature fetal movement quality. Although these data are limited by small sample size, the bioeffect index of in vivo platelet 5-HT transporter inhibition appears to provide a valuable approach for elucidating and possibly predicting the effects of gestational SRI exposure on fetal and perinatal neurobehavior.

Prenatal mercury exposure and the secondary sex ratio: The Japan Environment and Children's Study

Prior research into the association between prenatal mercury (Hg) exposure and the secondary sex ratio has yielded inconclusive and conflicting results. Notably, no study has used cord blood Hg measurement in this context. Also, the differences in Hg species and the potential modifying role of selenium (Se) on this association remain unexplored. Using data from the Japan Environment and Children's Study, we analyzed mother–child pairs with available data for concentrations of total mercury (THg) and Se in maternal blood during late pregnancy, and THg, inorganic mercury (IHg), methylmercury (MeHg), and Se in cord blood. Logistic regression models were employed to examine the association between Hg and Se biomarkers and the secondary sex ratio. Out of the total sample of 3698 children, 1877 (50.8 %) were male, corresponding to an overall secondary sex ratio of 1.03. After adjusting for maternal age and parity, no significant associations were observed between THg concentrations of maternal blood and the secondary sex ratio. Nevertheless, we identified that two-fold increases in THg, IHg, and MeHg concentrations in cord blood were positively associated with increased odds of having a male child, yielding adjusted odds ratios of 1.13 (95 %CI: 1.04, 1.22), 1.12 (1.03, 1.21), and 1.12 (1.03, 1.22), respectively. When stratified by the median Se concentrations, no apparent differences were detected in the associations between Hg concentrations and the secondary sex ratio. In summary, elevated Hg concentrations in cord blood, but not maternal blood, were associated with an increased probability of male births.

Exploring the association of hyperhomocysteinemia with early pregnancy losses: A retrospective case-control study in a tertiary clinic in Türkiye.

A disturbance in the metabolism of homocysteine in both the mother and the fetus has been implicated in several placental vasculopathy-related disorders, including pregnancy loss. This study aimed to provide insights into the potential role of homocysteine, Vitamin B12, and folic acid in early pregnancy losses, with a specific focus on the Turkish population. The results of 93 pregnant women who experienced miscarriage between 5 and 14 gestational weeks and 93 healthy pregnant women at the same gestational weeks were compared. The demographic and pregnancy characteristics of all pregnant women were recorded. Vitamin B12, folic acid, and homocysteine levels were measured in serum samples obtained from the groups at similar gestational weeks. In addition, any associations between these biomarkers and different types of pregnancy loss, such as spontaneous abortion and missed abortion, were evaluated. Vitamin B12 and folic acid serum levels were significantly lower in women with miscarriages (P = .019, P < .001, respectively). Homocysteine levels were higher in the patient group (P < .001). Logistic regression analysis showed that a higher homocysteine level was the only predictive factor of miscarriage (P = .001, odds ratio = 0.596); however, folic acid and Vitamin B12 were not predictive factors. There was no significant difference in homocysteine and micronutrient levels between women with missed abortions and women with spontaneous abortions (P > .05). Our results support the continuing evidence of a link between maternal homocysteine levels and fetal loss. However, in exploring the shared pathways in the underlying mechanisms causing the 2 forms of pregnancy loss, maternal blood analysis showed no relationship.

Bridging the Gap between Galectin-3 Expression and Hypertensive Pregnancy Disorders: A Narrative Review.

Galectin-3 belongs to a family of soluble glycan-binding proteins, which are increasingly recognized as modulators of pregnancy-associated processes, including proper placental development. Gestational hypertension and preeclampsia are significant complications of pregnancy, affecting millions of women annually. Despite their prevalence, the underlying pathophysiological mechanisms remain poorly understood. Several theories have been proposed, including inflammation, placental insufficiency, disturbed placental invasion, and angiogenesis. The Scopus and PubMed/MEDLINE databases were utilized until the end of May 2024. In total, 11 articles with 1011 patients, with 558 in the control group and 453 in the preeclampsia group, were included. Seven articles investigated the expression of galectin-3 (Gal-3) in placental tissue samples, eight studies calculated the serum levels of Gal-3 in maternal blood samples, while one study referred to the possible correlation of galectin-3 levels in umbilical cord blood. The results were inconsistent in both the placental tissue and maternal serum; Gal-3 placental expression was found to be statistically increased in five studies compared to that in women without gestational hypertensive disorders, while two studies either mentioned decreased expression or no difference. Similarly, the Gal-3 maternal serum levels, compared to those in women without gestational hypertensive disorders, were found to be statistically increased in five studies, while three studies did not find any statistical difference. Gal-3 can play a crucial role in the pathogenesis of preeclampsia, and its expression is influenced by gestational age and placental insufficiency. A further investigation ought to be conducted to enlighten the correlation of Gal-3 with gestational hypertension and preeclampsia development.

Protective Assets Reinforced With Integrated Care and Technology (PARITY): Protocol for a Randomized Controlled Trial.

Black women are significantly more likely to experience severe maternal morbidity and are 3 times as likely to die from pregnancy-related causes compared to White women. Using a strengths-based wellness approach within an integrated supportive care program provided by a community doula could offer pragmatic solutions for Black maternal disparities. The Protective Assets Reinforced with Integrated Care and Technology (PARITY) program consists of a wellness technology platform, including informational links to wellness content and reinforcing motivational SMS text messages, as well as community-based doula support delivered both in person and through the technology platform to improve Black maternal wellness. This pilot randomized controlled trial (RCT) and mixed methods evaluation aims to (1) determine the feasibility and acceptability of the PARITY intervention; (2) investigate the preliminary efficacy of the PARITY intervention on clinical outcomes (maternal blood pressure, gestational weight gain, and cesarean birth); and (3) investigate changes to wellness behavioral outcomes (nutrition, physical activity, sleep, and health care adherence) and empowered strengths (self-efficacy, social support, motivation, resilience, problem-solving, and self-regulation) in the intervention group compared to a control group. A 2-arm RCT and mixed methods evaluation will be conducted. Overall, 60 Black pregnant individuals will be randomized in a ratio of 1:1 to either the intervention or informational control group. Participants in the intervention group will receive access to the technology platform over a 12-week period that ends before birth. Intervention participants will be assigned a doula interventionist, who will meet with them 4 times during the intervention. All participants (intervention and control) will receive a referral for a birth doula at no cost, printed materials about having a healthy pregnancy, and community resources. Feasibility and acceptability will be assessed at the end of the program. Measures will be obtained at baseline (20-28 weeks), the 36th week of pregnancy, birth, and 6-12 weeks post partum. Summary statistics and distribution plots will be used to describe measured variables at each time point. A generalized linear mixed model with a shared random component will be used to analyze the effects of PARITY on clinical, wellness behavioral, and empowered strength outcomes, including baseline nutrition, physical activity, and sleep measures as covariates. For significant effects, post hoc contrasts will be adjusted using the Holm method to maintain comparison-wise error at or <.05. Missing data will be addressed using a pattern-mixture model. The National Institute of Nursing Research funded this pilot RCT. Recruitment, enrollment, and data collection are ongoing, and the estimated study completion date is October 2024. The expected results of this study will provide the feasibility and preliminary efficacy of the PARITY intervention, to be used in a larger trial with a 12-month PARITY program intervention. ClinicalTrials.gov NCT05802615; https://clinicaltrials.gov/study/NCT05802615. DERR1-10.2196/58580.

Circulating Cell-Free Mitochondrial DNA as a Novel Biomarker for Intra-Amniotic Infection in Obstetrics: A Pilot Trial.

Background/Objectives: Intra-amniotic infection (IAI) is a rare but serious condition with potential complications such as preterm labor and intrauterine fetal death. Diagnosing IAI is challenging due to varied clinical signs. Oxidative stress and mitochondrial dysfunction have been hypothesized to evolve around IAI. This study focused on measuring circulating mtDNA levels, a proposed biomarker for mitochondrial dysfunction, in maternal serum and placenta of women with confirmed IAI and healthy controls. Methods: 12 women with confirmed IAI (IAI group) were enrolled following premature preterm rupture of the membranes (PPROM) and compared to 21 healthy women (control group). Maternal blood was obtained two weeks pre-partum and peripartum; furthermore, postpartum placental blood was taken. In the IAI group, maternal blood was taken once weekly until delivery as well as peripartum, as was placental blood. Circulating cell-free mtDNA was quantified by real-time quantitative PCR. Results: Upon admission, in the IAI group, mean plasma mtDNA levels were 735.8 fg/μL compared to 134.0 fg/μL in the control group (p < 0.05). After delivery, in the IAI group, mean mtDNA levels in the placenta were 3010 fg/μL versus 652.4 fg/μL (p < 0.05). Conclusions: Circulating cell-free mtDNA could serve as a valuable biomarker for IAI prediction and diagnosis. Future research should establish reference values for sensitivity in predicting IAI.

Monocentric Study on the Performance of Noninvasive Prenatal Testing on Cell-Free DNA for the Detection of Monosomy X.

Increasing the PPV of monosomy X detected by the non-invasive prenatal test (NIPT) by discriminating a (mosaic) monosomy X genotype of fetal versus maternal origin. Out of 30,700 women referred for NIPT between January 2014 and December 2021, 79 had a high risk result for 45,X. Discrimination between fetal and maternal 45,X was made based on the values for ffX, ffY and SeqFF. Follow-up was provided through analysis of amniotic fluid, maternal blood, umbilical cord blood, neonatal blood and/or placental biopsies. Follow-up data were available for 70/79 women; after exclusion of one twin pregnancy, 69 pregnancies were evaluated (87.3%). Forty one of those were correctly predicted as being maternal or fetal, for an overall PPV of 59.4% (95% confidence interval [CI] 47%-71%). Of the 33 predicted fetal cases with follow-up, 11 were indeed of fetal origin, equating to a PPV of 33.3% (95% CI 18%-52%); three additional cases turned out to be placental in origin, six were maternal and for 13, no explanation could be found. The PPV of maternal cases was 88.2% (30/34 cases with follow-up correctly predicted; 95% CI 73%-97%). One case turned out to be fetal; for the other three, follow-up studies failed to prove the presence of monosomy X. Two cases for which no prediction on the origin of the monosomy X could be made (inconclusive high-risk NIPT result) turned out to have confined placental mosaicism. Although the PPV for fetal monosomy X remains lower than for the common trisomies, the total PPV for 45,X screening with NIPT can be improved by discerning fetal from (mosaic) maternal 45,X genotype. Thorough follow-up to determine the origin of the aberrant NIPT result is advised, so that women can be adequately counseled on the risk in their current and future pregnancies and, in case of maternal mosaic monosomy X, of their own prospects.

Quantification of ADHD medication in biological fluids of pregnant and breastfeeding women with liquid chromatography: a comprehensive review.

Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that has long been considered a concern only in the pediatric population. However, symptoms often sustain into adulthood and may require medication. For women with ADHD, this also means dealing with the disorder during the reproductive period. Medication safety during pregnancy and breastfeeding is a critical concern, and the potential transfer of ADHD medication to infants remains a topic of scientific interest. The quantification of ADHD medications in both maternal blood and breast milk are vital for understanding their pharmacokinetics and potential exposure risks for (nursing) infants. This review aims (1) to compile and critically assess existing research on the transfer of ADHD medications into breast milk and the potential implications for nursing infants and (2) to provide a comprehensive overview and discussion of the literature regarding the quantification of methylphenidate, amphetamine, atomoxetine, viloxazine, guanfacine, clonidine and bupropion in the blood, urine, oral fluid, and breast milk with liquid chromatography. A literature search was conducted using PubMed, Scopus, and Web of Science, to identify relevant articles published from January 2014 up to December 2023. We illustrate the lack of methods to simultaneously monitor multiple ADHD medications as well as the lack of developed methods for breast milk. Finally, we highlight the need for continued research to refine our understanding of medication transfer into breast milk and potential risks, and to develop clinical guidelines to support mothers with ADHD in making informed choices regarding medication use during pregnancy and lactation.

CffDNA screening for Niemann-pick disease, type C1: a case series.

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann-Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or had a first- or second-degree relative affected by the disorder. No specific criteria were set for the age of the participants. All were between 15 and 18 weeks of gestation. Using amplicon-based next-generation sequencing (NGS), we analyzed the zygosity and variants in cffDNA extracted from maternal peripheral blood. After amplicon NGS, analysis was completed by a custom data analysis pipeline that included in-house-built data processing scripts and commonly used software packages. Importantly, the results were not disclosed to the patients. Our findings showed that in all three cases, AR cffDNA screening results were consistent with standard invasive diagnostic testing. This screening method offers several advantages: it provides critical information to families earlier in the pregnancy compared to invasive diagnostic tests, and it helps to alleviate parental anxiety. Moreover, this non-invasive method can determine pregnancy status in the first trimester for known familial variants. Future research may extend this approach to screen for known disease-causing variants in common AR conditions.

Abstract We050: Elevated Cell-Free RNA in Maternal Circulation during Single Ventricle Heart Defect Pregnancies Dysregulate Human Cardiomyocyte Proliferation

Congenital single-ventricle heart defects (SVHDs) are life-threatening conditions in newborns, where one of the heart's ventricular chambers is severely underdeveloped. While medical advancements have improved survival rates, many SVHD patients still suffer lifelong cardiac complications and comorbidities. Clinical diagnosis of fetal SVHD occurs at around 20 weeks of gestation through echocardiogram. In this study, we aimed to identify novel maternal blood biomarkers that could signal SVHD development in fetuses. The study's premise is based on the limited regenerative capacity of adult human cardiomyocytes, like those in pregnant mothers, compared to the extensive proliferation seen in fetal cardiomyocytes that form the functional heart. We hypothesized small signaling molecules secreted by proliferating fetal cardiomyocytes enter the maternal circulatory system and could indicate abnormal ventricular growth in SVHD-affected fetuses. Both clinical and in vitro approaches were employed to identify potential cell-free miRNAs released by the developing fetal heart into maternal circulation. Blood plasma samples from pregnant women carrying healthy and SVHD-affected fetuses were screened for differentially expressed cell-free miRNAs and were compared with those from the supernatants of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) grown from healthy and SVHD donors. This comparative approach led to the identification of an miRNA panel (miR-487b, miR-433, mi-134, and miR-889) that were elevated in pregnant women carrying SVHD-affected fetuses and in proliferating iPSC-CMs from SVHD patients compared to healthy controls (p.adj&lt;0.05). From this panel, forced-expression of miR-487b and mir-134 modulated the proliferation profiles of human cardiomyocytes in vitro . Results from this study establish these circulating cell-free miRNAs in maternal blood as potential non-invasive biomarkers for predicting abnormal fetal cardiac development leading to SVHDs. These findings could potentially revolutionize SVHD screening as an alternative diagnostic tool to echocardiogram.

Identification of transcriptional signature change and critical transcription factors involved during the differentiation of mouse trophoblast stem cell into maternal blood vessel associated trophoblast giant cell

The placenta is essential organ for oxygen and nutrient exchange between the mother and the developing fetus. Trophoblast lineage differentiation is closely related to the normal function of the placenta. Trophoblast stem cells (TSCs) can differentiate into all placental trophoblast subtypes and are widely used as in vitro stem cell models to study placental development and trophoblast lineage differentiation. Although extensive research has been conducted on the differentiation of TSCs, the possible parallels between trophoblast giant cells (TGCs) that are differentiated from TSCs in vitro and the various subtypes of TGC lineages in vivo are still poorly understood. In this study, mouse TSCs (mTSCs) were induced to differentiate into TGCs, and our mRNA sequencing (RNA-seq) data revealed that mTSCs and TGCs have distinct transcriptional signatures. We conducted a comparison of mTSCs and TGCs transcriptomes with the published transcriptomes of TGC lineages in murine placenta detected by single-cell RNA-seq and found that mTSCs tend to differentiate into maternal blood vessel-associated TGCs in vitro. Moreover, we identified the transcription factor (TF) ZMAT1, which may be responsible for the differentiation of mTSCs into sinusoid TGCs, and the TFs EGR1 and MITF, which are likely involved in the differentiation of mTSCs into spiral artery-associated TGCs. Thus, our findings provide a valuable resource for the mechanisms of trophoblast lineage differentiation and placental deficiency-associated diseases development.

Early detection of pregnancy pathologies: Nucleic acid markers in maternal blood as a non-invasive strategy

Early detection of pregnancy pathologies: Nucleic acid markers in maternal blood as a non-invasive strategy

Integrating Multi-Omics with environmental data for precision health: A novel analytic framework and case study on prenatal mercury induced childhood fatty liver disease

BackgroundPrecision Health aims to revolutionize disease prevention by leveraging information across multiple omic datasets (multi-omics). However, existing methods generally do not consider personalized environmental risk factors (e.g., environmental pollutants). ObjectiveTo develop and apply a precision health framework which combines multiomic integration (including early, intermediate, and late integration, representing sequential stages at which omics layers are combined for modeling) with mediation approaches (including high-dimensional mediation to identify biomarkers, mediation with latent factors to identify pathways, and integrated/quasi-mediation to identify high-risk subpopulations) to identify novel biomarkers of prenatal mercury induced metabolic dysfunction-associated fatty liver disease (MAFLD), elucidate molecular pathways linking prenatal mercury with MAFLD in children, and identify high-risk children based on integrated exposure and multiomics data. MethodsThis prospective cohort study used data from 420 mother–child pairs from the Human Early Life Exposome (HELIX) project. Mercury concentrations were determined in maternal or cord blood from pregnancy. Cytokeratin 18 (CK-18; a MAFLD biomarker) and five omics layers (DNA Methylation, gene transcription, microRNA, proteins, and metabolites) were measured in blood in childhood (age 6–10 years). ResultsEach standard deviation increase in prenatal mercury was associated with a 0.11 [95% confidence interval: 0.02–0.21] standard deviation increase in CK-18. High dimensional mediation analysis identified 10 biomarkers linking prenatal mercury and CK-18, including six CpG sites and four transcripts. Mediation with latent factors identified molecular pathways linking mercury and MAFLD, including altered cytokine signaling and hepatic stellate cell activation. Integrated/quasi-mediation identified high risk subgroups of children based on unique combinations of exposure levels, omics profiles (driven by epigenetic markers), and MAFLD. ConclusionsPrenatal mercury exposure is associated with elevated liver enzymes in childhood, likely through alterations in DNA methylation and gene expression. Our analytic framework can be applied across many different fields and serve as a resource to help guide future precision health investigations.

Intrauterine administration of paternal and maternal peripheral blood mononuclear cells mix as solution for repeated implantation failure.

To date, implantation is the rate-limiting step for the success of in vitro fertilization (IVF) treatment. Accumulating evidence suggests that immune cells contribute to embryo implantation, and several therapeutic approaches have been proposed for the treatment of recurrent implantation failure (RIF). Endometrial immune modulation with autologous activated peripheral blood mononuclear cells (PBMCs) is one of the most widely used protocols. However, the effect of intrauterine insemination of mixed paternal and maternal-activated PBMCs has not yet been attempted and studied. The aim of our study is to test the effect of the addition of paternal lymphocytes on the implantation rate in RIF patients. Mononuclear cells were isolated from the peripheral blood of 98 RIF patients and cultured for 72h before insemination into the endometrial cavity 48h before embryo transfer. Our patients were divided into 4 groups according to the type and number of PBMCs inseminations. Our study shows that activated PBMCs promoted clinical pregnancy rates (CPR) in all groups. Moreover, we found that the groups injected with more than 2 million cells showed a better clinical outcome and, more interestingly, patients inseminated with both paternal and maternal activated PBMCs showed the highest CPR, reaching 47.2%, in addition to the highest implantation rate 31. 2% and the live birth rate 41.39%. Our work demonstrates the importance of administering a large number of activated PBMCs with the addition of paternal activated PBMCs to immunomodulate the endometrium for the success of in vitro fertilization in RIF patients.

Increased ultraprocessed consumption during pregnancy impacts essential fatty acid status in maternal and umbilical cord blood

Increased ultraprocessed consumption during pregnancy impacts essential fatty acid status in maternal and umbilical cord blood

First-trimester screening identifies maternal cardiac maladaptation in midgestation.

We have previously established that a logistic regression model, based on maternal demographic characteristics and blood pressure measured at 11-13 weeks' gestation, can identify about 70% of women who develop future chronic hypertension (CH) in the 3 years following pregnancy, at a screen-positive rate of 10%. Furthermore, in midgestation, women who subsequently develop hypertensive disorders of pregnancy (HDP) have increased peripheral vascular resistance and mild cardiac functional and morphological alterations and these cardiovascular abnormalities persist for at least 2 years after delivery. In this study, we set out to examine whether use of the first-trimester risk model for subsequent development of CH can help to identify women at high risk for cardiovascular maladaptation in midgestation. This was a prospective observational study of 3812 women with singleton pregnancy attending for a routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation and again at 19 + 1 to 23 + 3 weeks at King's College Hospital, London, UK, between December 2019 and August 2020. The first-trimester visit included recording of maternal demographic characteristics and medical history and measurement of systolic and diastolic blood pressure. In midgestation, detailed maternal cardiovascular assessment was carried out. The association between risk for development of CH, determined from first-trimester assessment, and cardiovascular indices in midgestation was examined. Women who were at high risk for development of future CH, compared to those at low risk, had a higher incidence of HDP. In addition, high-risk women had reduced systolic and diastolic function in midgestation. Among women with HDP, those who were at high risk for future CH, compared to those at low risk, had worse cardiac function in midgestation. Use of a model for first-trimester prediction of subsequent development of CH can identify women who show evidence of cardiac maladaptation in midgestation. Further studies are needed to clarify whether women who screen as high risk for future CH, compared to those at low risk, have reduced cardiac function beyond pregnancy. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Association of Phenols, Parabens, and Their Mixture with Maternal Blood Pressure Measurements in the PROTECT Cohort.

Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited. We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among Puerto Rico PROTECT study participants. We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes. We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB (95% CI: 0.17, 1.38) and adjusted P-PB (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted ; 95% CI: , ). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only. Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008.

Association of Maternal Air Pollution Exposure and Infant Lung Function Is Modified by Genetic Propensity to Oxidative Stress.

The association between air pollution and poor respiratory health outcomes is well established. Children are particularly at risk from air pollution, especially during the prenatal period as their organs and systems are still undergoing crucial development. This study investigated maternal exposure to air pollution during pregnancy and oxidative stress (OS), inflammation, and infant lung function at 4 weeks of age. Data from the Barwon Infant Study were available for 314 infants. The exposure to NO2 and PM2.5 were estimated. Infant lung function (4 weeks) was measured by multiple-breath washout. Glycoprotein acetyls (GlycA) (36 weeks prenatal), cord blood, and OS biomarkers were measured in maternal urine (28 weeks). A genetic pathway score for OS (gPFSox) was calculated. Linear regression was used and potential modification by the OS genotype was tested. There was no relationship between maternal exposure to air pollution and infant lung function, or with GlycA or OS during pregnancy. We found an association in children with a genetic propensity to OS between NO2 and a lower functional residual capacity (FRC) (β = -5.3 mls, 95% CI (-9.3, -1.3), p = 0.01) and lung clearance index (LCI) score (β = 0.46 turnovers, (95% CI 0.10, 0.82), p = 0.01). High prenatal exposure to ambient NO2 is associated with a lower FRC and a higher LCI score in infants with a genetic propensity to oxidative stress. There was no relationship between maternal exposure to air pollution with maternal and cord blood inflammation or OS biomarkers.