Gestational weight gain and daily life impact of pregnancy symptoms in healthy women: A multivariable analysis.

OBJECTIVE: To study the relationship between gestational weight gain (GWG) and Daily Life Impact of Pregnancy Symptoms (DLIPS) scores. METHODS: A multivariable analysis of a clinical trial (the Walking Preg_Project (WPP), ClinicalTrials.gov NCT03735381) was conducted. The cohort data concerning GWG across gestational trimesters (T1, T2 and T3) was categorized into adequate, excessive, and reduced based on published criteria. DLIPS was measured using the pregnancy symptoms inventory (PSI) a validated tool, across the gestational trimesters. Univariable and multivariable analyses were employed to assess the association between the GWG categories and DLIPS scores in each trimester of pregnancy estimating the ß-coefficients and 95% confidence intervals (CI). RESULTS: There were 221 participants in the cohort. DLIPS mean score in the overall sample and within adequate, excessive, and reduced GWG categories significantly increased across pregnancy (p < 0.005). DLIPS mean score was higher in the excessive GWG category compared to adequate and reduced GWG, in T1 and T2 (p = 0.035; p = 0.031, respectively). An excessive GWG at T1 [ß-coefficient (95 % CI) = 3.88, (0.84, 6.93)] and T2 [ß-coefficient (95 % CI) = 4.47 (1.24; 7.70)] was associated with higher DLIPS score compared to an adequate GWG. CONCLUSION: The impact of pregnancy symptoms on daily life increased throughout pregnancy, overall. Excessive GWG was associated with daily life impact of pregnancy symptoms, particularly in the first and second trimester.

Sexually dimorphic DNA methylation and gene expression patterns in human first trimester placenta.

BACKGROUND: Fetal sex and placental development impact pregnancy outcomes and fetal-maternal health, but the critical timepoint of placenta establishment in first trimester is understudied in human pregnancies. METHODS: Pregnant subjects were recruited in late first trimester (weeks 10-14) at time of chorionic villus sampling, a prenatal diagnostic test. Leftover placenta tissue was collected and stored until birth outcomes were known, then DNA and RNA were isolated from singleton, normal karyotype pregnancies resulting in live births. DNA methylation was measured with the Illumina Infinium MethylationEPIC BeadChip array (n = 56). Differential methylation analysis compared 25 females versus 31 males using a generalized linear model on 743,461 autosomal probes. Gene expression sex differences were analyzed with RNA-sequencing (n = 74). An integrated analysis was performed using linear regression to correlate gene expression and DNA methylation in 51 overlapping placentas. RESULTS: Methylation analysis identified 151 differentially methylated probes (DMPs) significant at false discovery rate < 0.05, including 89 (59%) hypermethylated in females. Probe cg17612569 (GABPA, ATP5J) was the most significant CpG site, hypermethylated in males. There were 11 differentially methylated regions affected by fetal sex, with transcription factors ZNF300 and ZNF311 most significantly hypermethylated in males and females, respectively. RNA-sequencing identified 152 genes significantly sexually dimorphic at false discovery rate < 0.05. The 151 DMPs were associated with 18 genes with gene downregulation (P < 0.05) in the direction of hypermethylation, including 2 genes significant at false discovery rate < 0.05 (ZNF300 and CUB and Sushi multiple domains 1, CSMD1). Both genes, as well as Family With Sequence Similarity 228 Member A (FAM228A), showed significant correlation between DNA methylation and sexually dimorphic gene expression, though FAM228A DNA methylation was less sexually dimorphic. Comparison with other sex differences studies found that cg17612569 is male-hypermethylated across gestation in placenta and in human blood up to adulthood. CONCLUSIONS: Overall, sex dimorphic differential methylation with associated differential gene expression in the first trimester placenta is small, but there remain significant genes that may be regulated through methylation leading to differences in the first trimester placenta.

Fetal sex and placenta development affect pregnancy outcomes for both the fetus and mother throughout pregnancy, including risk of miscarriages, preterm birth, preeclampsia, and other outcomes. Epigenetics, the "overlay" of regulatory signals on DNA which affects how DNA is read, is not well understood in early pregnancy when critical placenta developments are happening that affect the rest of pregnancy. Here, we use leftover placenta biopsy samples (n = 56) donated by Cedars-Sinai patients with informed consent to learn about first trimester human placenta DNA methylation differences due to fetal sex. Out of the total 743,461 sites analyzed, we identified 151 sites significantly affected by fetal sex after correcting p-values to reduce false positives (false discovery rate < 0.05). We also performed an analysis to look at multiple sites and identified 11 regions across the genome with significant DNA methylation changes due to fetal sex. Furthermore, because DNA methylation is a regulatory mark on DNA which typically dampens gene expression, we also compared the DNA methylation sex differences to placental RNA-sequencing gene expression analysis using the same tissue from a mostly overlapping patient group (n = 74 total sequenced, n = 51 overlap). We identify 18 genes which show both significant DNA methylation differences and gene expression changes. The most significant gene was transcription factor ZNF300 with higher DNA methylation in males and reduced gene expression in males (and thus higher gene expression in females). This study identifies some sex differences that continue until later pregnancy and others that are unique to first trimester.

Placental and serum levels of human α-Klotho in preeclampsia & intra-uterine growth retardation: A potential sensitive biomarker?

INTRODUCTION: α-Klotho protein has three isoforms: a transmembrane (mKL), a shed- soluble isoform, and a circulating soluble isoform (sKL). mKL is expressed in the kidney and placenta, while sKL is detectable in blood and urine. It is known that α-Klotho levels fluctuate during pregnancy mainly in women with complications such as preeclampsia (PE) and intra-uterine growth restriction (IUGR). METHODS: Forty-nine participants were divided into two groups: healthy and complicated pregnancy (PE, IUGR or both). Tissue samples (2 cm3) from the maternal side, Blood and urine samples were collected during pregnancy and postpartum. Samples were subjected to biochemical (WB), histological (H&E and IHC) staining as well as genetic analysis (qPCR). RESULTS: Blood αKL levels were preserved in both healthy and complicated pregnancies. Significantly lower blood αKL concentrations were found in PE postpartum (PP) compared to levels during pregnancy, and were significantly lower compared with postpartum of a healthy pregnancy. αKL activity was reduced in complicated pregnancies vs. healthy pregnancies. Placen tal mKL levels (ELISA) and expression (WB) were lowered in complicated pregnancies compared with the healthy pregnancies group. Additionally, we found a significant decline in the expression of mKL mRNA in PE/IUGR placentas compared with the healthy group. DISCUSSION: Several studies have focused on the involvement of αKL in normal placentation during pregnancy. Our results suggest lower function of sKL in complicated pregnancy compared with a control, and present differences in placental mKL levels as well as tissue and gene expression between healthy and complicated pregnancy. In light of our results, we conclude that complicated pregnancy is associated with in decline in mKL.

Health-related needs of survivors of hypertensive disorders of pregnancy: implications for health communication interventions.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are key contributors to maternal morbidity, mortality, and future risk of cardiovascular disease. This exploratory study aimed to unearth the health-related needs of women with a reported history of HDP by inquiring about preferences for care. METHOD: Deductive, qualitative analysis was conducted of HDP survivors' retrospective 'wishes' about the care received. RESULTS: In analyzing 244 open-ended, online survey responses, we identified a taxonomy of health-related needs arising across the trajectory of HDP: clinical information, needs requiring clinical knowledge, such as information about the etiology or prognosis of HDP; medical, needs associated with HDP intervention and management; logistical, needs regarding practical information, such as how to contact a provider or obtain the correct medical device; emotional, needs involving a desire for support or validation; and communication, needs for improved explanations and recognition of HDP. CONCLUSIONS: A taxonomy of diverse health-related needs may assist clinicians in approaching HDP patients more holistically. Additionally, opportunities exist for health communication research to inform standard approaches to HDP-related communication flowing from provider to patient.

The maternal microbiome in pregnancy, delivery, and early-stage development of neonatal microbiome after cesarean section: A prospective longitudinal study.

INTRODUCTION: Changes within the maternal microbiome during the last trimester of pregnancy and the determinants of the subsequent neonatal microbiome establishment after delivery by elective cesarean section are described. MATERIAL AND METHODS: Maternal vaginal and rectal microbiome samples were collected in the last trimester and before cesarean section; intrauterine cavity, placenta, neonatal buccal mucosa, skin, and meconium samples were obtained at birth; neonatal sample collection was repeated 2-3 days postnatally. Microbial community composition was analyzed by 16S rRNA gene amplicon sequencing. Relative abundance measurements of amplicon sequencing variants and sum counts at higher taxonomic levels were compared to test for significant overlap or differences in microbial community compositions. CLINICALTRIALS: gov ID: NCT04489056. RESULTS: A total of 30 mothers and their neonates were included with available microbiome samples for all maternal, intrauterine cavity and placenta samples, as well as for 18 of 30 neonates. The composition of maternal vaginal and rectal microbiomes during the last trimester of healthy pregnancies did not significantly change (permutational multivariate analysis of variance [PERMANOVA], p > 0.05). No robust microbial signature was detected in the intrauterine cavity, placenta, neonatal buccal mucosa, skin swabs, or meconium samples collected at birth. After birth, the neonatal microbiome was rapidly established, and significantly different microbial communities were detectable 2-3 days postnatally in neonate buccal mucosa and stool samples (PERMANOVA, p < 0.01). CONCLUSIONS: Maternal vaginal and rectal microbiomes in healthy pregnancies remain stable during the third trimester. No microbial colonization of the neonate was observed before birth in healthy pregnancies. Neonatal microbiomes in infants delivered by cesarean section displayed a taxonomic composition distinct from maternal vaginal and rectal microbiomes at birth, indicating that postnatal exposure to the extrauterine environment is the driving source of initial neonatal microbiome development in this cohort.

Phenotyping the autonomic nervous system in pregnancy using remote sensors: potential for complication prediction.

Objectives: The autonomic nervous system (ANS) plays a central role in dynamic adaptation during pregnancy in accordance with the pregnancy demands which otherwise can lead to various pregnancy complications. Despite the importance of understanding the ANS function during pregnancy, the literature lacks sufficiency in the ANS assessment. In this study, we aimed to identify the heart rate variability (HRV) function during the second and third trimesters of pregnancy and 1 week after childbirth and its relevant predictors in healthy pregnant Latina individuals in Orange County, CA. Materials and methods: N = 16 participants were enrolled into the study from which N = 14 (N = 13 healthy and n = 1 complicated) participants proceeded to the analysis phase. For the analysis, we conducted supervised machine learning modeling including the hierarchical linear model to understand the association between time and HRV and random forest regression to investigate the factors that may affect HRV during pregnancy. A t-test was used for exploratory analysis to compare the complicated case with healthy pregnancies. Results: The results of hierarchical linear model analysis showed a significant positive relationship between time (day) and average HRV (estimated effect = 0.06; p < 0.0001), regardless of being healthy or complicated, indicating that HRV increases during pregnancy significantly. Random forest regression results identified some lifestyle and sociodemographic factors such as activity, sleep, diet, and mental stress as important predictors for HRV changes in addition to time. The findings of the t-test indicated that the average weekly HRV of healthy and non-healthy subjects differed significantly (p < 0.05) during the 17 weeks of the study. Conclusion: It is imperative to focus our attention on potential autonomic changes, particularly the possibility of increased parasympathetic activity as pregnancy advances. This observation may challenge the existing literature that often suggests a decline in parasympathetic activity toward the end of pregnancy. Moreover, our findings indicated the complexity of HRV prediction, involving various factors beyond the mere passage of time. To gain a more comprehensive understanding of this dynamic state, future investigations should delve into the intricate relationship between autonomic activity, considering diverse parasympathetic and sympathetic metrics, and the progression of pregnancy.

Risk Factors for Alcohol Consumption after Starting Assisted Reproductive Technology Treatment among Japanese Women: Japan-Female Employment and Mental Health in Assisted Reproductive Technology (J-FEMA) Study.

AIMS: To determine the association between drinking habits and social factors among women undergoing assisted reproductive technology (ART) treatment in Japan. METHODS: The study participants who provided answers for the questionnaire concerning alcohol consumption were 1017 female patients undergoing ART treatment were enrolled in the Japan-Female Employment and Mental Health in assisted reproductive technology (J-FEMA) study between August and December 2018. Patient characteristics, including demographic, clinical, and socioeconomic status, were assessed using a self-administered questionnaire which was distributed only once during the period, regardless of their first or follow-up examination. We defined current drinkers who drank ≥46 g of ethanol per week as the habitual drinking group. The risk factors for habitual drinking were analyzed using multivariable-adjusted logistic regression. RESULTS: The proportion of habitual drinkers was 15.5% in this study population. The multivariable-adjusted odds ratios (95% confidence interval) for habitual drinking were 2.27 (0.99-5.21) for women aged ≥35 years versus those <35 years, 4.26 (1.98-9.16) for women having partners who currently drink compared to those with partners without current drinking, 1.84 (1.08-3.12) for women without a history of childbirth versus those with, and 1.77 (1.00-3.14) for working women compared with those not working. CONCLUSIONS: In our study, habitual drinking among women undergoing ART treatment was significantly associated with older age, no history of childbirth, partner's current drinking status, and working.

Trimester-specific reference intervals of hemostasis biomarkers for healthy pregnancy.

Physiological changes in hemostasis during pregnancy have been reported by several authors. This study aimed at establishing reference intervals for the hemostasis biomarkers thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), thrombomodulin (TM) and tissue plasminogen activator-inhibitor complex (tPAI-C), in healthy pregnancies. After excluding outliers, a total of 496 healthy pregnant women (128 first-trimester, 142 second-trimester, 107 third-trimester and 119 pre-labor) and 103 healthy nonpregnant women were enrolled from Shenzhen Bao'an Women's and Children's Hospital. Hemostasis biomarkers, TAT, PIC, TM and tPAI-C, were measured by using a quantitative chemiluminescence enzyme immunoassay performed on HISCL automated analysers. The median and reference intervals (the 2.5th and 97.5th percentiles) were calculated to establish trimester-specific reference intervals for healthy pregnant women. The reference intervals for TAT, PIC, TM and tPAI-C in the first trimester were 0.7-7.6 1 µg/L, 0.2-0.9 mg/L, 2.8-11.0 TU/ml, and 1.2-6.5 1 µg/L, respectively. The reference intervals in the second trimester were 1.7-12.0 1 µg/L, 0.2-1.0 mg/L, 3.7-11.6 TU/ml, and 2.8-8.8 1 µg/L, respectively. The reference intervals in the third trimester were 2.7-16.1 1 µg/L, 0.1-1.4 mg/L, 2.9-12.9 TU/ml, and 1.9-8.0 1 µg/L, respectively. At pre-labor, the reference intervals were 4.8-32.9 1 µg/L, 0.2-1.9 mg/L, 4.2-12.6 TU/ml, and 2.8-15.4 1 µg/L, respectively. Gestational reference intervals for TAT, PIC, TM and tPAI-C in healthy pregnancies are provided, but only for TAT with increasing concentrations throughout pregnancy, the reference intervals for non-pregnant were not applicable.

A Quality Improvement Innovation for Reproductive Health Planning in the Time of COVID.

OBJECTIVES: To see if an outreach approach with telehealth is feasible and acceptable to patients to talk about their reproductive health; and as a secondary outcome, capture data on time spent on the visit and what kind of information was discussed. METHODS: A registry was created from three family physicians' panels of all adult patients with anticipated ability to become pregnant ages 18-45 who had not had a documented reproductive health discussion in the previous 6 months. Using that registry, outreach was performed to schedule a telehealth visit to discuss their reproductive health with their primary care provider. The visit was standardized using the One Key Question approach. For patients who agreed to participate in the research, the patient completed a survey about their experience. The provider also completed a survey on the time spent and the issues addressed. RESULTS: Two hundred and six patients were called. Ninety patients (44%) could not be reached. Of the remaining patients, 34 scheduled either a telehealth or in-person visit and 7 also agreed to participate in the survey. New information was uncovered in the visit in 86% of participants. The most common need uncovered during the visit was unrelated medical needs (71%), followed by preconception health education/advice (43%) and contraception needs/counseling (29%). Most participants found the telehealth visit valuable. CONCLUSIONS: An outreach methodology can uncover unmet health needs, both reproductive and otherwise. We found that people who had the visit often needed something, but a majority of patients declined the visit saying that they did not think they needed it. It is possible that patients are not aware of the value of reproductive health discussions, and therefore clinicians need to take every opportunity to have these discussions whenever possible, whether through outreach or inreach (during already scheduled visits).

Alterations in Vessel Hemodynamics Across Uncomplicated Pregnancy.

Pregnancy is marked by the onset of rapid hemodynamic alterations in order to accommodate the needs of the developing fetus. Arterial stiffness is an independent predictor of cardiovascular events and mortality, and its measurement in clinical practice has been recommended. It follows a U-shaped curve in uncomplicated pregnancy, decreasing to a nadir in mid-pregnancy and rising at term. Systemic vasodilation occurs due to elevated nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, estrogen, progesterone, and relaxin. Vascular resistance decreases to a nadir in mid-pregnancy, while endothelial function is enhanced starting in the first trimester. Plasma volume increases by about 50%, and total red blood cell mass increases by up to 40%. Cardiac output increases by up to 45%, at first due primarily to elevated stroke volume, then mainly due to increased heart rate. Along with echocardiography, cardiac magnetic resonance imaging is safe for use in pregnancy. It may assess cardiac function more accurately than echocardiography, and may be indicated in specific clinical cases. Moreover, blood pressure decreases to a nadir in mid-pregnancy and rises to near preconception values postpartum. An appreciation of the vascular changes occurring in healthy pregnancy can aid in the prediction and diagnosis of pregnancy complications, such as preeclampsia and other hypertensive disorders of pregnancy, and inform treatment. In particular, noninvasive arterial stiffness/hemodynamics assessment provides unique clinical information beyond blood pressure and traditional maternal characteristics, and can signal a need for further testing, or be used in combination with other tests to predict or diagnose complications of pregnancy.

Quality Appraisal of Nutritional Guidelines to Prevent, Diagnose, and Treat Malnutrition in All Its Forms during Pregnancy.

This work aimed to identify clinical practice guidelines (CPGs) that include recommendations for the prevention, diagnosis, and treatment of women's malnutrition during pregnancy and to evaluate the quality of these guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. We conducted a literature review using PubMed and different websites from January 2009 to February 2021. The quality of the CPGs was independently assessed by reviewers using the AGREE II instrument, which defines guidelines scoring >70% in the overall assessment as "high quality". The analysis included 43 guidelines. Among the main findings, we identified that only half of the CPGs (51.1%) obtained a final "high quality" evaluation. AGREE II results varied widely across domains and categories. The two domains that obtained the highest scores were scope and purpose with 88.3% (range 39 to 100%) and clarity of presentation with 87.2% (range 25 to 100%). Among the "high quality" CPGs, the best scores were achieved by the three guidelines published by the National Institute of Health and Care Excellence (NICE) and the World Health Organization (WHO). Due to the importance of maternal nutrition in pregnancy, it is essential to join forces to improve the quality of the guidelines, especially in CPGs that do not meet the reference standards for quality.

Lifestyle, Maternal Nutrition and Healthy Pregnancy.

Healthy lifestyle habits spanning from preconception to postpartum are considered as a major safeguard for achieving successful pregnancies and for the prevention of gestational diseases. Among preconception priorities established by the World Health Organization (WHO) are healthy diet and nutrition, weight management, physical activity, planned pregnancy and physical, mental and psychosocial health. Most studies covering the topic of healthy pregnancies focus on maternal diet because obesity increases the risks for adverse perinatal outcomes, including gestational diabetes mellitus, large for gestational age newborns, or preeclampsia. Thus, foods rich in vegetables, essential and polyunsaturated fats and fibre-rich carbohydrates should be promoted especially in overweight, obese or diabetic women. An adequate intake of micronutrients (e.g. iron, calcium, folate, vitamin D and carotenoids) is also crucial to support pregnancy and breastfeeding. Moderate physical activity throughout pregnancy improves muscle tone and function, besides decreasing the risk of preeclampsia, gestational diabesity (i.e. diabetes associated with obesity) and postpartum overweight. Intervention studies claim that an average of 30 min of exercise/day contributes to long-term benefits for maternal overall health and wellbeing. Other factors such as microbiome modulation, behavioural strategies (e.g. smoking cessation, anxiety/stress reduction and sleep quality), maternal genetics and age, social class and education might also influence the maternal quality of life. These factors contribute to ensure a healthy pregnancy, or at least to reduce the risk of adverse maternal and foetal outcomes during pregnancy and later in life.

Turkish reference ranges for the left fetal modified myocardial performance index.

BACKGROUND: This study aimed to assess fetal cardiac left ventricular function in healthy pregnant women by calculating the modified myocardial performance index (Mod-MPI) and to construct reference ranges for the Turkish population. METHODS: One-hundred-two randomly selected healthy singleton pregnant women ranging between 25 and 39 gestational weeks were included in the study. Left fetal Mod-MPI was measured for each pregnant woman. Women with chronic systemic diseases or fetuses with chromosomal or structural abnormalities were excluded from the study. Mitral valve (MV) and aortic valve (AoV) clicks were used as landmarks to define the following time periods that were used to calculate the Mod-MPI: isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET). RESULTS: The mean Mod-MPI was 0.42±0.10. The mean IRT, ICT, and ET were 43.5±10.2, 27.27±8.1, and 170.5±16.9, respectively. A significant correlation was found between Mod-MPI and gestational age, umbilical artery systolic/diastolic (UA S/D) ratio and the middle cerebral artery pulsatility index (MCA PI) values (r=0.199, p=0.047, r=-0.328, p=0.001, and r=-0.0349, p=0.001, respectively) Conclusions. The current study`s results will be a reference for future studies, especially studies investigating pathological conditions that impact fetal cardiac function.

Association between neutrophil to lymphocyte ratio and carotid artery wall thickness in healthy pregnant women.

OBJECTIVE: Pregnancy may elicit a state of mild inflammation that might affect, either directly or indirectly, haematological parameters associated with systemic inflammation. In particular, both Neutrophil-to-lymphocyte ratio (NLR) and Red blood cells Distribution Width (RDW) have been found to be elevated in complicated pregnancy. However, data regarding the association of these haematological parameters with common carotid artery (CCA) intima-media thickness (IMT) in healthy pregnancy are scanty. Aim of this study was to evaluate possible changes in CCA-IMT during normal pregnancy and in the postpartum period, and to correlate these changes with NLR and RDW. STUDY DESIGN: Between October 2019 and February 2020, a prospective study was carried out on 73 consecutive healthy pregnant women (32.8 ± 4.9 yrs/old). Women underwent obstetric assessment, complete blood cell counts with calculation of NLR and RDW, two-dimensional transthoracic echocardiography and carotid Doppler ultrasonography. RESULTS: During normal pregnancy, both NLR and RDW progressively increased (p < 0.0001); likewise, parameters of carotid dimensions also significantly increased (p < 0.0001). Hematological and morphological changes all decreased in postpartum period. By univariable logistic regression, the variables which showed the greatest independent association with CCA-IMT (defined as CCA-IMT ≥0.55 mm) were: age (HR 1.33, 95% CI 1.15-1.53, p < 0.0001), pre-pregnant BMI (HR 2.75, 95% CI 1.72-4.41, p < 0.0001), third trimester E/e' ratio (HR 1.64, 95% CI 1.34-2.02, p < 0.0001), and third trimester NLR (HR 3.00, 95% CI 1.64-5.50, p < 0.0001). Multivariable logistic regression analysis demonstrated that third trimester NLR was the only variable that retained statistical significance (HR 2.49, 95% CI 1.35-4.59, p = 0.003). An NLR ≥ 2 reached 83% of sensitivity and 99% of specificity in identifying a CCA-IMT ≥0.55 mm (AUC = 0.95). A strong linear correlation of both third trimester NLR and RDW with CCA-IMT was observed (r = 0.89 and 0.83, respectively). CONCLUSIONS: Pregnancy is a state of chronic mild inflammation and the progressive increase in NLR and RDW during normal pregnancy is significantly associated with CCA intimal-medial thickening.

Multiprofessional care promotes of quality of life in pregnant women with preeclampsia: a cross-sectional study

OBJECTIVES: To assess the quality of life of hospitalized pregnant women with preeclampsia (PE), and compare with a group of healthy pregnant women (HP). METHODS: This was an observational cross-sectional study conducted among 58 pregnant women; 28 of them had preeclampsia and 30 were healthy. The WHOQOL-Bref questionnaire, which was divided into four aspects: physical, psychological, social, and environmental, was applied to each subject. RESULTS: A statistically significant difference was observed regarding maternal age (PE 27.8±6.2 x HG 23.0±6.6, p<0.01) and gestational age (PE 224±28.1 x HG 253.8±43.7, p<0.01) in relation to the clinical and obstetric data. No significant difference was observed among groups in the physical (PE 57.7±18.9 x HG 65.7±16.6, p=0.19), psychological (PE 68.2±12.8 x HG 73.3±13.30, p=0.16), social (PE 72.0±15.8 x HG 71.7±18.7, p=0.78), or environmental (PE 61.1±11.9 x HG 59.3±15.9, p=0.88) aspects of the WHOQOL-Bref. CONCLUSIONS There was no difference in quality of life between the groups studied, a result possibly due to the fact that women with PE were hospitalized and received multiprofessional care.

Interleukin-7, T helper 1, and regulatory T-cell activity-related cytokines are increased during the second trimester of healthy pregnancy compared to non-pregnant women.

PROBLEM: Healthy pregnancy is associated with a physiologic increase in inflammatory responses. The objective of this study was to assess changes in plasma cytokines associated with uncomplicated pregnancy. METHOD OF STUDY: To examine these changes, plasma levels of immune response mediators from healthy gravidas (N = 115, gestation weeks 23-30) were compared with those from healthy non-pregnant women (N = 42). Comparisons were performed using multiplex analysis for Th1 activity-related cytokines (IFN-γ, IL-2, sIL-2Rα, IL-12[P70], and IL-27), Th2 activity-related cytokines (IL-4, IL-5, and IL-13), other immune response mediators (GM-CSF, IL-1ß, sIL-1RI, IL-6, IL-8, IL-15, IL-17A, IL-17F, IL-21, IL-22, IL-23, TGFß1, TGFß2, TGFß3, and TNFα), regulatory T cell-related cytokines (IL-10 and sTNFRII), adipokines (adiponectin, leptin, PAI-1, and resistin), chemokines (IP-10, MCP-1, and MIP-1ß), and hematopoietic growth factor IL-7. RESULTS: Multivariate linear regression models showed increased levels of IL-7, Th1-, and Treg activity-related cytokines and decreased levels of adipokines and chemokines in healthy gravidas compared with healthy non-pregnant women. Additionally, season of the year, age, pre-pregnancy body mass index, and HLA-DR/DQ genotypes for type 1 diabetes risk showed different and sometimes reciprocal influence on cytokine levels. CONCLUSION: Our study stresses the importance of profiling immune response mediators during pregnancy to better understand the effect of healthy pregnancy on cytokine levels.

Factors Influencing the Quality of Life of Healthy Pregnant Women in North Jordan.

Background and Objectives: Quality of life (QOL) assessment during pregnancy contributes to determining women's unmet needs and preventing negative health outcomes. In this study, we aimed to identify the effects of participants' characteristics, perceived stress, and perceived social support on their QOL. We also aimed to determine the differences in QOL according to these factors. Materials and Methods: A cross-sectional study was carried out in a city in Jordan. Purposive sampling was used to select 218 participants. Data was collected by the quality of life Short Form- 36(SF-36) survey, perceived stress scale (PSS), and The Multidimensional perceived Social Support Scale (MSPSS). Results: We found that only parity had a significant effect on the QOL. High-parity women had lower QOL scores than low-parity women. The participants reported high social support, specifically from their families and significant others. The 36-Item Short-Form Health Survey was a reliable tool for measuring the QOL in pregnancy. Conclusions: Parity factor and social support should be recognized in any health promotion intervention and during providing antenatal care. Further research is needed toassess the QOL during pregnancy.

Reference intervals for hemoglobin A1c (HbA1c) in healthy Mexican pregnant women: a cross-sectional study.

BACKGROUND: The reference intervals for hemoglobin A1c (HbA1c) in pregnant Mexican women without diabetes are not well defined. The study aims to determine the reference intervals for HbA1c at each trimester in healthy Mexican pregnant women. METHODS: This cross-sectional study included healthy Mexican pregnant women in trimester 1 (T1), 6-13.6 weeks of gestation (WG), trimester 2 (T2), 14-27 WG, and trimester 3 (T3), ≥27-36 WG, with a maternal age > 18 years, and pregestational body mass index (BMI) ranging between 18.5-24.9 kg/m2. Women with gestational diabetes mellitus, pregestational diabetes, anemia, a pregestational BMI < 18.5 or ≥ 25 kg/m2, and any hematologic, hepatic, immunological, renal, or cardiac disease were excluded. HbA1c was measured using high-performance liquid chromatography based on the National Glycohemoglobin Standardization Program-certified PDQ Primus guidelines. The HbA1c reference intervals were calculated in terms of the 2.5th to the 97.5th percentiles. RESULTS: We analyzed the HbA1c values of 725 women (T1 n = 84, T2 n = 448, and T3 n = 193). The characteristics of the participants were expressed as mean ± standard deviation and included: maternal age (28.2 ± 6.7 years), pregestational weight (54.8 ± 5.9 Kg), pregestational BMI (22.2 ± 1.7 Kg/m2), and glucose values using a 75 g-2 h oral glucose tolerance test; fasting 4.5 ± 0.3 mmol/L (81.5 ± 5.5 mg/dL), 1 h 6.4 ± 1.5 mmol/L (115.3 ± 26.6 mg/dL), and 2 h 5.7 ± 1.1 mmol/L (103.5 ± 19.6 mg/dL). Reference intervals for HbA1c, expressed as median and 2.5th to 97.5th percentile for each trimester were: T1: 5.1 (4.5-5.6%), T2: 5.0 (4.4-5.5%), and T3: 5.1 (4.5-5.6%). CONCLUSIONS: The reference range of HbA1C in healthy Mexican pregnant women during pregnancy was 4.4% to 5.6%. We suggest as upper limits of HbA1c value ≤5.6%, 5.5%, and 5.7% for T1, T2, and T3, respectively among Mexican pregnant women.

Deep Surveying of the Transcriptional and Alternative Splicing Signatures for Decidual CD8+ T Cells at the First Trimester of Human Healthy Pregnancy.

Decidual CD8+ (dCD8) T cells have been proposed to play important roles in immune protection against the invading pathogens and in tolerance toward the growing semi-allogeneic fetus during early pregnancy. However, their phenotypic and functional characteristics remain poorly defined. Here, we performed the first analysis of the transcriptional and alternative splicing (AS) signatures for human first-trimester dCD8 T cells using high-throughput mRNA sequencing. Our data revealed that dCD8 T cells have distinct transcriptional and AS landscapes when compared with their autologous peripheral blood CD8+ (pCD8) T counterparts. Furthermore, human dCD8 T cells were observed to contain CD8-Treg and effector-memory T-cell subsets, and display enhanced functionality in terms of degranulation and cytokine production on a per-cell basis. Additionally, we have identified the novel splice junctions that use a high ratio of the non-canonical splicing motif GC-AG and found that AS is not a major contributor to the gene expression-level changes between paired pCD8 and dCD8 T cells. Together, our findings not only provide a comprehensive framework of the transcriptional and AS landscapes but also reveal the functional feature of human dCD8 T cells, which are of great importance in understanding the biology of these cells and the physiology of human healthy pregnancy.

Serum nitric oxide levels in healthy pregnant women: a case- control study in a tertiary facility in Ghana.

BACKGROUND: Pregnancy is associated with significant changes in maternal cardiovascular system which regulates oxygen and nutrient supply to the growing foetus. Nitric oxide, a physiologic vascular smooth muscle relaxant regulates blood flow and therefore may play a role in the cardiovascular changes in pregnancy. The study aimed to determine the levels and changes in maternal serum nitric oxide levels during healthy pregnancy. METHODS: A case-control study was conducted among 32 healthy non-pregnant women as controls and 100 healthy pregnant women (consisting of 33 first trimester, 37 s trimester, and 30 third trimester) as cases. Subjects were consecutively recruited into the study after obtaining an informed consent and meeting the inclusion criteria. Griess Reagent method was used to determine serum nitric oxide levels. RESULTS: There were no statistically significant difference in the ages and parity of recruited cases and controls. Mean arterial blood pressures were significantly lower (p = 0.009) and serum nitric oxide levels were significantly higher (p < 0.001) in healthy pregnant women compared to healthy non-pregnant women. There was a non-significant progressive increase in serum nitric oxide levels during healthy normal pregnancy. CONCLUSIONS: The finding of a significantly reduced blood pressures and a significant increase in serum nitric oxide levels in healthy pregnancy may suggest a role of nitric oxide in vascular adaptation in pregnancy.