Potential Risk Factors for Developing Cesarean Scar Pregnancy in Women With a History of Cesarean Section.

OBJECTIVES: Cesarean scar pregnancy (CSP) occurs in 0.2%-0.5% of women with a previous cesarean section globally. Multiple factors influence the development of CSP; however, to date, the critical factors contributing to the development of CSP have not been fully explored due to its relatively low incidence. Moreover, CSP can be clinically categorized into type 1 and type 2 CSP. In this retrospective study with a large sample size, we investigated potential risk factors that could contribute to CSP development. METHODS: Two hundred-one women diagnosed with CSP, either type 1 or type 2 CSP, and 1700 pregnant women with a history of cesarean section but without CSP diagnosis in subsequent pregnancy were included. Gravidity, previous live birth(s), consecutive cesarean section(s), surgical abortion(s), the interval between the pregnancies, and maternal age were compared between the 2 groups. RESULTS: Gravidity, the number of previous live births, the number of previous consecutive cesarean sections, and the number of surgical abortions were significantly associated with CSP development in women with a past cesarean section. This association was regardless of the subtypes of CSP. Notably, the interval between 2 pregnancies was also significantly associated with CSP development, but this association was only seen in type 2 CSP. However, maternal age was not an independent risk factor for CSP development. Additionally, a higher incidence of CSP was observed in China compared to that reported in the literature. CONCLUSION: In addition to a previous cesarean section, our study highlights at the number of surgical abortions also contributes to the development of CSP.

Associations between reproductive factors and the prevalence of depression: findings from the National Health and Nutrition Examination Survey (NHANES) 2005-2018.

BACKGROUND: This study aims to explore the relationship between female reproductive factors (age at first birth (AFB), age at last birth (ALB), gravidity, and number of live birth (NLB)) and prevalence of depression among the US women. METHODS: The relationship between AFB, ALB, gravidity, and NLB with the prevalence of depression was explored using publicly available data from the National Health and Nutrition Examination Survey 2005-2018. This cross-sectional study included female participants aged 20 years and older, with reproductive factors and depressive symptoms reported by the participants. Depression was evaluated using the Patient Health Questionnaire-9, with a score of ≥ 10 representing major depression disorder. Weighted multivariable logistic regression and restricted cubic splines (RCS) were utilized to explore the association of AFB, ALB, gravidity and NLB with depression. RESULTS: In this study of 11,488 US women, 1,332 (11.6%) women had depression. Compared to the reference group of women with AFB under 18 years, the fully adjusted ORs and 95% CIs for depression were 0.83 (95% CI: 0.68-0.99), 0.75 (95% CI: 0.60-0.95), and 0.69 (95% CI: 0.51-0.93) for women with AFB of 21-23, 24-26, and 27-29 years, respectively. Furthermore, women with five or more pregnancies had a significantly higher prevalence of depression compared to those with two or fewer pregnancies (OR = 1.20, 95% CI: 1.01-1.42). RCS models demonstrated linear associations of ALB, gravidity and NLB with the prevalence of depression. Additionally, the RCS analysis revealed a roughly L-shaped relationship between AFB and prevalence of depression. CONCLUSIONS: Women with later AFB are associated with a decreased prevalence of depression, while multiple pregnancies are associated with an increased prevalence of depression. These findings suggest that reproductive factors should be considered when screening for and developing preventive strategies for depression.

Validity of self-reported number of pregnancies and maternal age at first birth among females attending organized mammographic screening.

AIMS: Reproductive history conveys information about potential health risks later in adulthood. This study aimed to examine the validity of self-reported number of pregnancies and maternal age at first birth (AFB) among females attending BreastScreen Norway. METHODS: Participants were identified through the Janus Serum Bank cohort in Norway and were eligible for this cross-sectional validation study if they participated in a health survey issued by BreastScreen Norway between 2006 and 2015. Retrospective self-reported survey information on number of pregnancies and AFB in years was validated against prospectively collected information from the Medical Birth Registry of Norway (MBRN) using the Spearman rank (rs) and intraclass correlation coefficients (ICC) with 95% confidence intervals (CI). RESULTS: After exclusions, 51,598 subjects were included in the analysis on number of pregnancies and 46,919 in the analysis on AFB. On average, study subjects were 59-60 years old when completing the health survey and had become first-time mothers roughly 36 years earlier. Survey-based information about number of pregnancies was highly correlated and demonstrated high agreement with the registry data (rs=0.967, 95% CI 0.964-0.969; ICC=0.884, 95% CI 0.882-0.885). Survey-based information about AFB demonstrated even higher correlation and very high agreement with the registry data (rs=0.975, 95% CI 0.973-0.976; ICC=0.974, 95% CI 0.974-0.975). CONCLUSIONS: Retrospectively recalled survey-based information about number of pregnancies and AFB was highly accurate when validated against prospectively collected information in the MBRN. These survey-based data are valuable for future epidemiological research, and linkage to the MBRN may not be required when these data are available.

Are pelvic-abdominal mechanics exercises effective for cesarean delivery rate and postpartum pelvic floor function: A randomized controlled trial.

OBJECTIVES: To examine the effectiveness of pelvic-abdominal mechanics exercise in reducing cesarean section rates and preventing pelvic floor dysfunction in primiparous women. DESIGN: Randomized controlled trial. METHODS: A single-center prospective study was conducted among 200 primiparous participants (aged 18-38 years) who undertook formal card-issuing maternity tests between June 1, 2022, and June 30, 2023. Participants were divided into two groups: exercise (intervention) and control using the random number table method. Participants of the intervention group performed pelvic-abdominal mechanics exercise at least 1 h each time per week for three months. Participants of the control group did not perform any pelvic-abdominal mechanics exercise during pregnancy. This study conducted a comprehensive evaluation from three perspectives, including maternal and neonatal health outcomes during delivery, the recovery status of pelvic floor muscles at 42 days postpartum, and the quality of life during late pregnancy (36-38 weeks) and 42 days postpartum. RESULTS: A significant difference was found in delivery outcomes. The cesarean section rates are significantly higher (p < 0.05) in the control group (36 %) than in the exercise group (19 %). At 42 days postpartum, pelvic floor assessment showed that the exercise group had significantly better results in pelvic floor muscle strength compared to the control group, with statistical significance (p < 0.05). CONCLUSIONS: Pelvic-abdominal mechanics exercise lowers the rate of cesarean section and improves postpartum pelvic floor function.

Is gravidity associated with COVID-19 vaccination among pregnant women in Jamaica?

Introduction: In 2021, Jamaica's maternal mortality ratio doubled as a result of COVID-19-related deaths. Yet, COVID-19 vaccination among pregnant Jamaican women remained low. In the United States, COVID-19 vaccination is lower among pregnant women who have had multiple pregnancies (multigravidas) versus women who were pregnant for the first time (primigravidas). We examined whether this pattern exists in Jamaica. Methods: A cross-sectional survey of a convenience sample of 79 pregnant Jamaican women recruited from a teaching hospital (May-July 2022) was used to assess self-reported COVID-19 vaccination and medical mistrust beliefs-operationalized as low vaccine confidence, government mistrust, and race-based mistrust-by gravidity. We used modified Poisson regression to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for vaccination by gravidity, adjusting for age, education, and comorbidities. Results: Thirty-nine (49%) of the participants were multigravidas. Socioeconomic status was similar between multigravidas and primigravidas. COVID-19 vaccination was lower in multigravidas (46%) than primigravidas (75%) after adjusting for age, education, and comorbidities (aPR = 0.67, 95% CI = 0.46-0.99; p = 0.044). Vaccine confidence was lower in multigravidas (p = 0.044). Government mistrust and race-based mistrust did not differ between the two groups. Conclusion: In Jamaica, multigravidas may have lower COVID-19 vaccine uptake and lower vaccine confidence compared with primigravidas. Understanding the distinct needs of pregnant subpopulations is essential for crafting effective maternal vaccination campaigns.

Gravidity influences distinct transcriptional profiles of maternal and fetal placental macrophages at term.

Introduction: Maternal intervillous monocytes (MIMs) and fetal Hofbauer cells (HBCs) are myeloid-derived immune cells at the maternal-fetal interface. Maternal reproductive history is associated with differential risk of pregnancy complications. The molecular phenotypes and roles of these distinct monocyte/macrophage populations and the influence of gravidity on these phenotypes has not been systematically investigated. Methods: Here, we used RNA sequencing to study the transcriptional profiles of MIMs and HBCs in normal term pregnancies. Results: Our analyses revealed distinct transcriptomes of MIMs and HBCs. Genes involved in differentiation and cell organization pathways were more highly expressed in MIMs vs. HBCs. In contrast, HBCs had higher expression of genes involved in inflammatory responses and cell surface receptor signaling. Maternal gravidity influenced monocyte programming, as expression of pro-inflammatory molecules was significantly higher in MIMs from multigravidae compared to primigravidae. In HBCs, multigravidae displayed enrichment of gene pathways involved in cell-cell signaling and differentiation. Discussion: Our results demonstrated that MIMs and HBCs have highly divergent transcriptional signatures, reflecting their distinct origins, locations, functions, and roles in inflammatory responses. Furthermore, maternal gravidity influences the gene signatures of MIMs and HBCs, potentially modulating the interplay between tolerance and trained immunity. The phenomenon of reproductive immune memory may play a novel role in the differential susceptibility of primigravidae to pregnancy complications.

Hydrogen sulfide and its role in female reproduction.

Hydrogen sulfide (H2S) is a gaseous signaling molecule produced in the body by three enzymes: cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S is crucial in various physiological processes associated with female mammalian reproduction. These include estrus cycle, oocyte maturation, oocyte aging, ovulation, embryo transport and early embryo development, the development of the placenta and fetal membranes, pregnancy, and the initiation of labor. Despite the confirmed presence of H2S-producing enzymes in all female reproductive tissues, as described in this review, the exact mechanisms of H2S action in these tissues remain in most cases unclear. Therefore, this review aims to summarize the knowledge about the presence and effects of H2S in these tissues and outline possible signaling pathways that mediate these effects. Understanding these pathways may lead to the development of new therapeutic strategies in the field of women's health and perinatal medicine.

A sonographic endometrial thickness <7 mm in women undergoing in vitro fertilization increases the risk of placenta accreta spectrum.

BACKGROUND: The prevalence of placenta accreta spectrum, a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening methods and early identification strategies for placenta accreta spectrum could enable early treatment and improved outcomes. Endometrial thickness plays a crucial role in successful embryo implantation and favorable pregnancy outcomes. Extensive research has been conducted on the impact of endometrial thickness on assisted reproductive technology cycles, specifically in terms of pregnancy rates, live birth rates, and pregnancy loss rates. However, limited knowledge exists regarding the influence of endometrial thickness on placenta accreta spectrum. OBJECTIVE: This study aimed to evaluate the association between preimplantation endometrial thickness and the occurrence of placenta accreta spectrum in women undergoing assisted reproductive technology cycles. STUDY DESIGN: A total of 4637 women who had not undergone previous cesarean delivery and who conceived by in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment and subsequently delivered at the Third Affiliated Hospital of Guangzhou Medical University between January 2008 and December 2020 were included in this study. To explore the relationship between endometrial thickness and placenta accreta spectrum, we used smooth curve fitting, threshold effect, and saturation effect analysis. Multivariate logistic regression analysis was performed to evaluate the independent association between endometrial thickness and placenta accreta spectrum while adjusting for potential confounding factors. Propensity score matching was performed to reduce the influence of bias and unmeasured confounders. Furthermore, we used causal mediation effect analysis to investigate the mediating role of endometrial thickness in the relationship between gravidity and ovarian stimulation protocol and the occurrence of placenta accreta spectrum. RESULTS: Among the 4637 women included in this study, pregnancies with placenta accreta spectrum (159; 3.4%) had significantly thinner endometrial thickness (non-placenta accreta spectrum, 10.08±2.04 mm vs placenta accreta spectrum, 8.88±2.21 mm; P<.001) during the last ultrasound before embryo transfer. By using smooth curve fitting, it was found that changes in endometrial thickness had a significant effect on the incidence of placenta accreta spectrum up to a thickness of 10.9 mm, beyond which the effect plateaued. Then, the endometrial thickness was divided into the following 4 groups: ≤7, >7 to ≤10.9, >10.9 to ≤13, and >13 mm. The absolute rates of placenta accreta spectrum in each group were 11.91%, 3.73%, 1.35%, and 2.54%, respectively. Compared with women with an endometrial thickness from 10.9 to 13 mm, the odds of placenta accreta spectrum increased from an adjusted odds ratio of 2.27 (95% confidence interval, 1.33-3.86) for endometrial thickness from 7 to 10.9 mm to an adjusted odds ratio of 7.15 (95% confidence interval, 3.73-13.71) for endometrial thickness <7 mm after adjusting for potential confounding factors. Placenta previa remained as an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 11.80; 95% confidence interval, 7.65-18.19). Moreover, endometrial thickness <7 mm was still an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 3.91; 95% confidence interval, 1.57-9.73) in the matched cohort after PSM. Causal mediation analysis revealed that approximately 63.9% of the total effect of gravidity and 18.6% of the total effect of ovarian stimulation protocol on placenta accreta spectrum were mediated by endometrial thickness. CONCLUSION: The findings of our study indicate that thin endometrial thickness is an independent risk factor for placenta accreta spectrum in women without previous cesarean delivery undergoing assisted reproductive technology treatment. The clinical significance of this risk factor is slightly lower than that of placenta previa. Furthermore, our results demonstrate that endometrial thickness plays a significant mediating role in the relationship between gravidity or ovarian stimulation protocol and placenta accreta spectrum.

Dysregulation of mucosal-associated invariant T cells correlates with altered placental microenvironment in preterm birth.

Preterm birth (PTB) is a major problem affecting perinatal health, directly increasing the mortality risk of mother and infant that often results from the breakdown of the maternal-fetal immune balance. Increasing evidence shows the essential role of mucosal-associated invariant T (MAIT) cells to balance antibacterial function and immune tolerance function during pregnancy. However, the phenotype and function of placental MAIT cells and their specific mechanisms in PTB remain unclear. Here, we report that MAIT cells in placentas from PTBs show increased activation levels and decreased IFN-γ secretion capacity compared with those from normal pregnancies. Moreover, our data indicate gravidity is a factor affecting placental MAIT cells during pregnancies. Multi-omics analysis indicated aberrant immune activation and abnormal increase of lipids and lipid-like metabolites in the PTB placental microenvironment. Moreover, the proportion and activation of MAIT cells were positively correlated with the abnormal increase of lipids and lipid-like metabolites. Together, our work revealed that abnormal activation and impaired function of MAIT cells may be related to abnormal elevation of lipids and lipid-like metabolites in PTB.

Gravidity modifies the associations of age and spousal age difference with couple's fecundability: a large cohort study from China.

STUDY QUESTION: Do couple's age ranges for optimal fecundability, and the associations with fecundability of couple's age combinations and age differences differ with gravidity? SUMMARY ANSWER: The couple's age range of optimal fecundability and age combinations differed with gravidity, and gravidity might modify the associations of age and spousal age difference with couple's fecundability. WHAT IS KNOWN ALREADY: Age is one of the strongest determinants of fecundability, but the existing studies have certain limitations in study population, couple's extreme age combinations and age differences, and have not explored whether the association between age and fecundability differs with gravidity. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study. 5 407 499 general reproductive-aged couples (not diagnosed with infertility) participated in the National Free Pre-conception Check-up Projects during 2015-2017. They were followed up for pregnancy outcomes through telephone interviews every 3 months until they became pregnant or were followed up for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: The main outcome was time to pregnancy, and the fecundability odds ratios and 95% CIs were estimated using the Cox models for discrete survival time. The associations of age and spousal age difference with fecundability were evaluated by restricted cubic splines. MAIN RESULTS AND THE ROLE OF CHANCE: In this large cohort of general reproductive-aged population, the age of optimal fecundability of multigravida couples was older than that of nulligravida couples, but their subsequent fecundability declined more sharply with age. The decline in female fecundability was more pronounced with age, with fecundability dropping by ∼30% in both nulligravida and multigravida couples whose female partners aged ≥35 years. In the nulligravida group, the fecundability of couples who were both ≤24 years with the same age was the highest, which decreased steadily with the increase of spousal age difference, and younger male partners did not seem to contribute to improving couple's fecundability. In the multigravida group, couples with female partners aged 25-34 years and a spousal age difference of -5 to 5 years showed higher fecundability, and the effect of spousal age difference on couple's fecundability became suddenly apparent when female partners aged around 40 years. Young male partners were unable to change the decisive effect of female partner's age over 40 years on couple's reduced fecundability, regardless of gravidity. LIMITATIONS, REASONS FOR CAUTION: Lacking the time for couples to attempt pregnancy before enrollment, and some couples might suspend pregnancy plans during follow-up because of certain emergencies, which would misestimate the fecundability. Due to the lack of information on sperm quality and sexual frequency of couples, we could not adjust for these factors. Moreover, due to population characteristics, the extrapolation of our results required caution. WIDER IMPLICATIONS OF THE FINDINGS: The couple's age range of optimal fecundability, age combinations, and spousal age difference on fecundability varied with gravidity. Female age-related decline in fecundability was more dominant in couple's fecundability. Targeted fertility guidance should be provided to couples with different age combinations and gravidities. STUDY FUNDING/COMPETING INTEREST(S): This research received funding from the Project of National Research Institute for Family Planning (Grant No. 2018NRIFPJ03), the National Key Research and Development Program of China (Grant No. 2016YFC1000307), and the National Human Genetic Resources Sharing Service Platform (Grant No. 2005DKA21300), People's Republic of China. The funders had no role in study design, analysis, decision to publish, or preparation of the manuscript. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Sex- and state-dependent covariation of risk-averse and escape behavior in a widespread lizard.

Mounting evidence has shown that personality and behavioral syndromes have a substantial influence on interspecific interactions and individual fitness. However, the stability of covariation among multiple behavioral traits involved in antipredator responses has seldom been tested. Here, we investigate whether sex, gravidity, and parasite infestations influence the covariation between risk aversion (hiding time within a refuge) and escape response (immobility, escape distance) using a viviparous lizard, Zootoca vivipara, as a model system. Our results demonstrated a correlation between risk-averse and escape behavior at the among-individual level, but only in gravid females. We found no significant correlations in either males or neonates. A striking result was the loss of association in postparturition females. This suggests that the "risk-averse - escape" syndrome is ephemeral and only emerges in response to constraints on locomotion driven by reproductive burden. Moreover, parasites have the potential to dissociate the correlations between risk aversion and escape response in gravid females, yet the causal chain requires further examination. Overall, our findings provide evidence of differences in the association between behaviors within the lifetime of an individual and indicate that individual states, sex, and life stages can together influence the stability of behavioral syndromes.

Associations of reproductive and breastfeeding history with anti-Müllerian hormone concentration among African-American women of reproductive age.

RESEARCH QUESTION: Are gravidity, parity and breastfeeding history associated with anti-Müllerian hormone concentration among African-American women of reproductive age? DESIGN: This study included baseline data from the Study of the Environment, Lifestyle and Fibroids, a 5-year longitudinal study of African-American women. Within this community cohort, data from 1392 women aged 25-35 years were analysed. The primary outcome was serum anti-Müllerian hormone concentration measured using the Ansh Labs picoAMH assay, an enzyme-linked immunosorbent assay. Multivariable linear regression models were used to estimate mean differences in anti-Müllerian hormone concentration (ß) and 95% CI by self-reported gravidity, parity and breastfeeding history, with adjustment for potential confounders. RESULTS: Of the 1392 participants, 1063 had a history of gravidity (76.4%). Of these, 891 (83.8%) were parous and 564 had breastfed. Multivariable-adjusted regression analyses found no appreciable difference in anti-Müllerian hormone concentration between nulligravid participants and those with a history of gravidity (ß = -0.025, 95% CI -0.145 to 0.094). Among participants with a history of gravidity, there was little difference in anti-Müllerian hormone concentration between parous and nulliparous participants (ß = 0.085, 95% CI -0.062 to 0.232). There was also little association between anti-Müllerian hormone concentration and breastfeeding history (ever versus never: ß = 0.009, 95% CI -0.093 to 0.111) or duration of breastfeeding (per 1-month increase: ß = -0.002, 95% CI -0.010 to 0.006). CONCLUSIONS: Gravidity, parity and breastfeeding history were not meaningfully associated with anti-Müllerian hormone concentration in this large sample of the Study of the Environment, Lifestyle and Fibroids cohort.

Obstetric and psychiatric history as predictors for psychosomatic symptoms among Korean perimenopausal women.

OBJECTIVES: Menopause presents various physical and psychological disturbances for women and comes at a high financial cost. Therefore, this study aimed to identify factors influencing menopause symptoms. STUDY DESIGN: Data of Korean perimenopausal women aged 40-60 (n = 1060; mean age, 46.03 ± 4.08) were collected by a research company. Participants were classified into a "functional" group (n = 716) or a "dysfunctional" group (n = 344) according to the severity of their perimenopausal psychosomatic symptoms. To investigate the association of obstetric and psychiatric history with membership of the "dysfunctional" group, a hierarchical logistic regression analysis was conducted. RESULTS: The outcomes of all three hierarchical logistic regression models presented significant overall model fit. Among the independent variables, family history of menopausal symptoms, menarcheal age, number of pregnancies, history of postpartum depression, postpartum psychosis, and other psychiatric disorders were positively associated with being in the "dysfunctional" group, whereas age and number of deliveries were negatively associated with being in the "dysfunctional" group. CONCLUSION: A short reproductive period and short exposure to estrogen due to late menarche and early menopausal transition may be related to severe perimenopausal symptoms. The relationship between the history of postpartum mental illness and severe perimenopausal symptoms may be associated with heightened sensitivity to hormonal triggers when a woman is exposed to fluctuating ovarian sex steroid levels. The relationship between parity or gravidity and the severity of menopausal symptoms in Korean women differed from that in studies conducted in other countries, possibly due to the low birth rate in Korea.

The global prevalence of gallstones in pregnancy: A systematic review and meta-analysis.

Background: Gallstone disease is the second most common non-gynecological disease that may require surgical intervention during pregnancy. This study investigates the global prevalence of gallstones in pregnancy through a systematic review and meta-analysis. Methods: A systematic review and meta-analysis of studies that reported the global prevalence of gallstones in pregnancy was conducted. PubMed, Scopus, Web of Science, Embase, ScienceDirect, and Google Scholar were searched for studies published up to September 2022. Results: In a review of 31 studies with a sample size of 190,714 people, the I2 heterogeneity test showed high heterogeneity (I2 = 98.8%). Therefore, the random effects method was used to analyze the results. The prevalence of gallstones was reported as 3.6% (95% CI: 1.9-6.7%). The highest prevalence of gallstones by continent was reported in America, at 6.8% (95% CI: 4.2-10.8%). The Egger test showed no evidence of publication bias (p = 0.609). Conclusion: Based on the results of this study, health policymakers should emphasize to the target community and the medical staff dealing with pregnant women the importance of screening for gallstones during pregnancy.

Malaria-specific Type 1 regulatory T cells are more abundant in first pregnancies and associated with placental malaria.

BACKGROUND: Malaria in pregnancy (MIP) causes higher morbidity in primigravid compared to multigravid women; however, the correlates and mechanisms underlying this gravidity-dependent protection remain incompletely understood. We aimed to compare the cellular immune response between primigravid and multigravid women living in a malaria-endemic region and assess for correlates of protection against MIP. METHODS: We characterised the second trimester cellular immune response among 203 primigravid and multigravid pregnant women enrolled in two clinical trials of chemoprevention in eastern Uganda, utilizing RNA sequencing, flow cytometry, and functional assays. We compared responses across gravidity and determined associations with parasitaemia during pregnancy and placental malaria. FINDINGS: Using whole blood RNA sequencing, no significant differentially expressed genes were identified between primigravid (n = 12) and multigravid (n = 11) women overall (log 2(FC) > 2, FDR < 0.1). However, primigravid (n = 49) women had higher percentages of malaria-specific, non-naïve CD4+ T cells that co-expressed IL-10 and IFNγ compared with multigravid (n = 85) women (p = 0.000023), and higher percentages of these CD4+ T cells were associated with greater risks of parasitaemia in pregnancy (Rs = 0.49, p = 0.001) and placental malaria (p = 0.0073). These IL-10 and IFNγ co-producing CD4+ T cells had a genomic signature of Tr1 cells, including expression of transcription factors cMAF and BATF and cell surface makers CTLA4 and LAG-3. INTERPRETATION: Malaria-specific Tr1 cells were highly prevalent in primigravid Ugandan women, and their presence correlated with a higher risk of malaria in pregnancy. Understanding whether suppression of Tr1 cells plays a role in naturally acquired gravidity-dependent immunity may aid the development of new vaccines or treatments for MIP. FUNDING: This work was funded by NIH (PO1 HD059454, U01 AI141308, U19 AI089674, U01 AI155325, U01 AI150741), the March of Dimes (Basil O'Connor award), and the Bill and Melinda Gates Foundation (OPP 1113682).

Gravid status is not associated with postoperative nausea and vomiting: a matched case-control study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common and unpleasant complication of general anesthesia. There are well-known risk factors that predispose a patient to develop PONV. While studies exist that explore PONV incidence in gravid and non-gravid women separately, limited studies exist to compare the two cohorts to identify if pregnancy is associated with increased risk for PONV or differences in PONV prophylaxis and treatment. METHODS: This is a retrospective case-control cohort study, with 1:2 matching based on age, year of surgery, and surgical procedure. Electronic medical records were abstracted for demographic information, predisposing risk factors, prophylactic antiemetics, PONV documentation, rescue antiemetics, PACU stay, and length of hospitalization. Analyses of risk factors for PONV were performed using logistic and multinomial logistic regression analyses. RESULTS: 237 gravid women who underwent non-obstetric procedures with general anesthesia were identified and matched with 474 non-gravid women. PONV complicated the course of 51 (21.5%) gravid and 72 (15.2%) non-gravid women. The number of prophylactic antiemetics was fewer among gravid (median 2 [1, 2]) than non-gravid (3 [2, 3]) women (P < 0.001). No association was found between gravid status and risk for PONV (adjusted odds ratio 1.35 [95%CI 0.84, 2.17], P = 0.222). Gravid women had longer hospital lengths of stay (P < 0.001), despite having shorter surgical duration (P = 0.015). CONCLUSIONS: The risk for PONV is similar between gravid and similarly aged women. However, anesthesiologists administer fewer prophylactic antiemetics to gravid women during non-obstetric surgery.

Trimester-specific reference intervals and profile of coagulation parameters for Chinese pregnant women with diverse demographics and obstetric history: a cross-sectional study.

BACKGROUND: Owing to the changes in childbirth policy in China, this work aimed to update the trimester-specific reference intervals (RIs) for Chinese pregnant women with diverse demographics and obstetric history. This study also investigated how advanced maternal age (AMA) (> 35 years old), gravity, and parity influence gestational coagulation parameters. METHODS: In this prospective cross-sectional study, five coagulation parameters were measured using assays provided by Roche diagnostics on Cobas t 711: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), and D-dimer, and the trimester-specific 2.5th -97.5th and 95th (D-dimer only) percentiles RIs were established accordingly. Linear regressions were undertaken to analyze the association with demographic characteristics and obstetric history for each parameter. RESULTS: 893 eligible pregnant women in different trimesters and at AMA/non-AMA and 275 non-pregnant healthy women were enrolled. For the first, second, and third trimester, respectively, RIs were as follows: APTT (s): 24.8-35.7, 24.6-34.1, and 23.5-34.7; TT (s): 14.4-17.3, 14.1-16.7, and 14.2-17.5; PT (s): 8.30-10.20, 8.00-9.77, and 7.92-9.57; PT-INR: 0.86-1.06, 0.83-1.02, and 0.82-0.98; Fib (g/L): 2.76-4.97, 3.14-5.31, and 3.44-5.93; D-dimer (µg/ml): 0-0.969, 0-2.14, and 0-3.28. No statistically significant differences were observed in TT, D-dimer, and APTT between the AMA and non-AMA women, while PT and PT-INR were shorter and Fib was higher in the AMA group. The association of gravidity and parity with each coagulation parameter is statistically significant (p < 0.05). PT and PT-INR were shortened and D-dimer decreased as gravidity increased. Longer PT and PT-INR, shorter APPT, higher D-Dimer, and lower Fib were associated with increasing parity. CONCLUSIONS: This work updated the gestational coagulation profiles of Chinese pregnant women and established trimester-specific RIs accordingly. Establishing specific RIs based on AMA, parity, and gravidity might not be necessary.

Anti-phosphatidylserine antibody levels are low in multigravid pregnant women in a malaria-endemic area in Nigeria, and do not correlate with anti-VAR2CSA antibodies.

Anemia is a common malaria-associated complication in pregnant women in endemic regions. Phosphatidylserine (PS) is exposed to the immune system during the massive destruction of red blood cells (RBCs) that accompany malaria, and antibodies against PS have been linked to anemia through destruction of uninfected RBCs. We determined levels of anti-PS IgG antibodies in pregnant women in Ibadan, Nigeria and correlated them to parameters of importance in development of anemia and immunity. Anti-PS correlated inversely with Packed Cell Volume (PCV), indicating that the antibodies could contribute to anemia. There was no correlation with anti-VAR2CSA IgG, haptoglobin or parasitemia, indicating that the modulation of anti-PS response is multifactorial in nature. Anti-PS levels were lowest in multigravidae compared to both primigravidae and secundigravidae and correlated inversely with age. In conclusion, lower levels of anti-PS in multigravidae could be beneficial in avoiding anemia.

Prevalence of hepatitis E virus and its association with adverse pregnancy outcomes in pregnant women in China.

BACKGROUND: Hepatitis E virus (HEV) infection has become a global concern, especially in pregnant women. However, the association between HEV prevalence and age, gravidity and parity of pregnant women remains unclear. METHODS: Pregnant women (n=19,762) were enrolled for HEV prevalence and associated adverse pregnancy outcomes investigation in Qujing City, Yunnan Province of China from May 2019 to December 2020. RESULTS: The seroprevalence of HEV was 11.6% (2,297/19,762; 95% CI:11.2%-12.1%). About 11.4% (2,247/19,762; 95% CI:10.9%-11.8%) were positive for anti-HEV IgG antibody, 0.1% (22/19,762; 95% CI:0.1%-0.2%) were positive for anti-HEV IgM antibody, and 0.1% (28/19,762; 95% CI:0.1%-0.2%) were positive for both anti-HEV IgM and IgG antibodies. Sixty-one out of 2,297 anti-HEV-antibodies-positive pregnant women were positive for HEV RNA. Phylogenetic analysis revealed that all HEV isolates from pregnant women belong to genotype 4. Age, gravidity and parity are associated with increased prevalence of HEV. Pregnant women positive for HEV-IgG antibody bear a higher risk for an adverse pregnancy history and liver injury with elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels than anti-HEV-negative pregnant women. Furthermore, seropositive pregnant women suffered a higher adverse maternal outcomes risk (crude odds ratio [cOR]=1.29; 95% CI: 1.16-1.43; adjusted odds ratio [aOR]=1.40, 95% CI: 1.25-1.55 for anti-HEV-IgG-positive pregnant women and cOR=1.38, 95% CI: 1.02-1.86; aOR=1.43, 95% CI: 1.05-1.95 for anti-HEV-IgM-positive pregnant women) and fetal outcomes risk (cOR=1.80, 95% CI: 1.61-2.01; aOR=1.77, 95% CI: 1.57-1.99) than anti-HEV-negative pregnant women. Adverse pregnancy outcomes of HEV infection are aggravated by age, gravidity and parity. CONCLUSION: In this study, we demonstrated high prevalence of HEV in pregnancy women in China, and HEV infection can cause various adverse maternal and neonatal outcomes.