Association between plasma leptin and cesarean section after induction of labor: a case control study

Background Obesity in pregnancy is common, with more than 50% of pregnant women being overweight or obese. Obesity has been identified as an independent predictor of dysfunctional labor and is associated with increased risk of failed induction of labor resulting in cesarean section. Leptin, an adipokine, is secreted from adipose tissue under the control of the obesity gene. Concentrations of leptin increase with increasing percent body fat due to elevated leptin production from the adipose tissue of obese individuals. Interestingly, the placenta is also a major source of leptin production during pregnancy. Leptin has regulatory effects on neuronal tissue, vascular smooth muscle, and nonvascular smooth muscle systems. It has also been demonstrated that leptin has an inhibitory effect on myometrial contractility with both intensity and frequency of contractions decreased. These findings suggest that leptin may play an important role in dysfunctional labor and be associated with the outcome of induction of labor at term. Our aim is to determine whether maternal plasma leptin concentration is indicative of the outcome of induction of labor at term. We hypothesize that elevated maternal plasma leptin levels are associated with a failed term induction of labor resulting in a cesarean delivery. Methods In this case-control study, leptin was measured in 3rd trimester plasma samples. To analyze labor outcomes, 174 women were selected based on having undergone an induction of labor (IOL), (115 women with successful IOL and 59 women with a failed IOL). Plasma samples and clinical information were obtained from the UI Maternal Fetal Tissue Bank (IRB# 200910784). Maternal plasma leptin and total protein concentrations were measured using commercially available assays. Bivariate analyses and logistic regression models were constructed using regression identified clinically significant confounding variables. All variables were tested at significance level of 0.05. Results Women with failed IOL had higher maternal plasma leptin values (0.5 vs 0.3 pg, P = 0.01). These women were more likely to have obesity (mean BMI 32 vs 27 kg/m2, P = 0.0002) as well as require multiple induction methods (93% vs 73%, p = 0.008). Logistic regression showed Bishop score (OR 1.5, p < 0.001), BMI (OR 0.92, P < 0.001), preeclampsia (OR 0.12, P = 0.010), use of multiple methods of induction (OR 0.22, P = 0.008) and leptin (OR 0.42, P = 0.017) were significantly associated with IOL outcome. Specifically, after controlling for BMI, Bishop Score, and preeclampsia, leptin was still predictive of a failed IOL with an odds ratio of 0.47 (P = 0.046). Finally, using leptin as a predictor for fetal outcomes, leptin was also associated with of fetal intolerance of labor, with an odds ratio of 2.3 (P = 0.027). This association remained but failed to meet statistical significance when controlling for successful (IOL) (OR 1.5, P = 0.50). Conclusions Maternal plasma leptin may be a useful tool for determining which women are likely to have a failed induction of labor and for counseling women about undertaking an induction of labor versus proceeding with cesarean delivery.

Associations of maternal plasma and infant umbilical cord blood plasma metabolomics profiles with anthropometric measures at birth: a prospective cohort study.

BackgroundThe metabolomics profiles of maternal plasma during pregnancy and cord plasma at birth might influence fetal growth and birth anthropometry. The objectives of this study are to examine how metabolites measured in maternal plasma samples collected during pregnancy and umbilical cord plasma samples collected at birth are associated with newborn anthropometric measures, a known predictor of future health outcomes.MethodsPregnant women between 24 and 28 weeks of gestation were recruited from prenatal clinics in New Hampshire as part of a prospective cohort study. Blood samples from 413 women at enrollment and 787 infant cord blood samples were analyzed using the Biocrates AbsoluteIDQ® p180 kit . Multivariable linear regression models were used to examine association of cord and maternal metabolites with infant anthropometry at birth.ResultsIn cord blood samples, several acylcarnitines, a phosphatidylcholine, and a custom metabolite indicator were negatively associated with birth weight Z-score, and lysophosphatidylcholines as well as three custom metabolite indicators were positively associated with birth weight Z-score. Acylcarnitine C5 was negatively associated with birth length Z-score, and several lysophosphatidylcholines and a custom metabolite indicator were positively associated with birth length Z-score. Maternal blood metabolites did not show significant associations with birth weight and length Z scores, however, a custom metabolite indicator, the ratio of kynurenine over tryptophan, was negatively associated with weight-for-length Z-score.ConclusionsSeveral cord blood metabolites associated with newborn weight and length Z-scores; in particular, consistent findings were observed for several acylcarnitines that play a role in utilization of energy sources, and a lysophosphatidylcholine that is part of oxidative stress and inflammatory response pathways. Fewer associations were observed with maternal metabolomic profiles.

Study on the Correlation between the Levels of HtrA3 and TGF-β2 in Late Pregnancy and Preeclampsia

Preeclampsia (PE) is a common and proprietary complication during pregnancy. The correlation was found between the levels of HtrA3 and TGF-β 2 and preeclampsia (PE). This study aimed to detect the HtrA3 and TGF-β2 in different parts of the third trimester (maternal serum, placenta). The 102 pregnant women who were eligible for enrollment in the obstetric examination at Tengzhou Maternity and Child Health Hospital from June 2020 to December 2020 were selected as the research objects. 28 cases diagnosed with PE were set up as the observation group 1, and 24 cases diagnosed with severe PE were set up as the observation group 2. Select 50 normal pregnant women as the control group and research the expressions of HtrA3 and TGF-β2 in maternal blood and placental tissues of patients with PE. ELISA was used to measure the concentration of HtrA3 and TGF-β2 in maternal blood. The distribution of HtrA3 and TGF-β2 in the placenta was observed by immunohistochemical techniques (IHC) and mean optical density value (MOD). S/D was measured by using color Doppler ultrasonic. The concentration of HtrA3 and TGF-β2 in the maternal blood and placenta tissue was higher in severe PE compared with PE and normotensive pregnancy, respectively ( P < 0.05 ). There is a negative correlation between the level of HtrA3 and TGF-β2 and the birthweight of newborns both in maternal plasma and placenta tissue in preeclampsia and positive correlation between HtrA3 and TGF-β2 levels and S/D. HtrA3 and TGF-β2 may correlate with severity of PE and their neonatal adverse outcomes.

Noninvasive Prenatal Testing of Methylmalonic Acidemia cblC Type Using the cSMART Assay for MMACHC Gene Mutations

Noninvasive prenatal testing (NIPT) for monogenic disorders has been developed in recent years; however, there are still significant technical and analytical challenges for clinical use. The clinical feasibility of NIPT for methylmalonic acidemia cblC type (cblC type MMA) was investigated using our circulating single-molecule amplification and re-sequencing technology (cSMART). Trios molecular diagnosis was performed in 29 cblC type MMA-affected children and their parents by traditional Sanger sequencing. In the second pregnancy, invasive prenatal diagnosis (IPD) of the pathogenic MMACHC gene was used to determine fetal genotypes, and NIPT was performed using a novel MMACHC gene–specific cSMART assay. Maternal–fetal genotypes were deduced based on the mutation ratio in maternal plasma DNA. Concordance of fetal genotypes between IPD and NIPT, and the sensitivity and specificity of NIPT were determined. After removing two cases with a low P value or reads, the concordance ratio for NIPT and IPD was 100.00% (27/27), and the sensitivity and specificity were 100.00% (54.07–100.00%) and 100.00% (83.89–100.00%), respectively. This study demonstrates that NIPT using the cSMART assay for cblC type MMA was accurate in detecting fetal genotypes. cSMART has a potential clinical application as a prenatal diagnosis and screening tool for carrier and low-risk genotypes of cblC type MMA and other monogenic diseases.

Mild Choline Deficiency and MTHFD1 Synthetase Deficiency Interact to Increase Incidence of Developmental Delays and Defects in Mice

Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80–90% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficiency on maternal one-carbon metabolism and reproductive outcomes in the MTHFD1-synthetase deficient mouse (Mthfd1S), a model for MTHFD1 R653Q. Mthfd1S+/+ and Mthfd1S+/− females were fed control (CD) or choline-deficient diets (ChDD; 1/3 the amount of choline) before mating and during pregnancy. Embryos were evaluated for delays and defects at 10.5 days gestation. Choline metabolites were measured in the maternal liver, and total folate measured in maternal plasma and liver. ChDD significantly decreased choline, betaine, phosphocholine, and dimethylglycine in maternal liver (p < 0.05, ANOVA), and altered phosphatidylcholine metabolism. Maternal and embryonic genotype, and diet-genotype interactions had significant effects on defect incidence. Mild choline deficiency and Mthfd1S+/− genotype alter maternal one-carbon metabolism and increase incidence of developmental defects. Further study is required to determine if low choline intakes contribute to developmental defects in humans, particularly in 653QQ women.

The regulatory network played by miRNAs during normal pregnancy and preeclampsia: a comparative study

Background: Preeclampsia is a pregnancy-specific syndrome, characterized by hypertension, proteinuria, and edema. Affecting between 2% and 8% of gestations worldwide, it accounts for 10% to 15% of maternal deaths. Although its etiology remains unclear, it includes complex pathological processes involving microRNAs, small non-coding RNA molecules with post-transcriptional repression effects on target mRNAs. Objective: To assess the expression of miRNAs during normal pregnancies and those complicated by preeclampsia, a sample of Venezuelan women were studied. Method: Nine placental microRNAs (hsa-miR- 20a-5p, 21-3p, 26a-5p, 181a-5p, 199a-5p, 210-3p, 222-5p, 223-3p, 424-3p) were measured in maternal plasma during the second and third trimesters of normal pregnancies, using a SYBR Green®-based real-time PCR, and compared the results against women affected by preeclampsia. Results: All assessed miRNAs were detected in maternal plasma in pregnancies with and without preeclampsia. All except miR-222 were over-expressed during disease when compared to the second and to third-trimester controls. miR-20a, miR-21, miR-26a, and miR-223 were down-regulated in the third trimester in comparison to the second trimester in normal pregnancies. Conclusion: The variation of the miRNAs expression through normal pregnancies suggested their involvement in normal physiological pregnancy processes. In contrast, the significant deregulation of the nine studied miRNAs during preeclampsia indicated the involvement of their target genes in the pathogenesis of the disease. miR-199a and miR-21-3p showed the greatest changes in expression. This study shows for the first time the presence of miR-20a, miR-199, and miR-424 and the variations they undergo in the plasma of pregnant women with preeclampsia.

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Many studies have confirmed that extrachromosomal circular DNAs (eccDNAs/ecDNAs) exist in tumor and normal cells independently of the chromosome and are essential for oncogene plasticity and drug resistance. Studies have confirmed that there are many eccDNAs/ecDNAs in maternal plasma derived from the fetus. Fetal growth restriction (FGR) is a pregnancy-related disease associated with high newborn morbidity and mortality. However, the characteristics and nature of eccDNAs/ecDNAs in FGR are poorly understood. This study aims to deconstruct the properties and potential functions of eccDNAs/ecDNAs in FGR. We performed circle-seq to identify the expression profile of eccDNAs/ecDNAs, analyzed by bioinformatics, and verified by real-time Polymerase Chain Reaction (PCR) combined with southern blot in FGR compared with the normal groups. A total of 45,131 eccDNAs/ecDNAs (including 2,118 unique ones) were identified, which had significantly higher abundance in FRG group than in normal group, and was bimodal in length, peaking at ~146bp and ~340bp, respectively. Gestational age may be one independent factor affecting the production of eccDNAs/ecDNAs, most of which come from genomic regions with high gene density, with a 4~12bp repeat around the junction, and their origin had a certain genetic preference. In addition, some of the host-genes overlapped with non-coding RNAs (ncRNAs) partially or even completely. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that host-genes on the differentially expressed eccDNAs/ecDNAs (DEEECs/DEECs) were mainly enriched in immune-related functions and pathways. The presence of some ecDNAs were verified, and whose variability were consistent with the circle-seq results. We identified and characterized eccDNAs/ecDNAs in placentas with FGR, and elucidated the formation mechanisms and the networks with ncRNAs, which provide a new vision for the screening of new biomarkers and therapeutic targets for FGR.