Maternal Age Research Articles

Protein biomarker signatures of preeclampsia - a longitudinal 5000-multiplex proteomics study

We aimed to explore novel biomarker candidates and biomarker signatures of late-onset preeclampsia (LOPE) by profiling samples collected in a longitudinal discovery cohort with a high-throughput proteomics platform. Using the Somalogic 5000-plex platform, we analyzed proteins in plasma samples collected at three visits (gestational weeks (GW) 12–19, 20–26 and 28–34 in 35 women with LOPE (birth ≥ 34 GW) and 70 healthy pregnant women). To identify biomarker signatures, we combined Elastic Net with Stability Selection for stable variable selection and validated their predictive performance in a validation cohort. The biomarker signature with the highest predictive performance (AUC 0.88 (95% CI 0.85–0.97)) was identified in the last trimester of pregnancy (GW 28–34) and included the Fatty acid amid hydrolase 2 (FAAH2), HtrA serine peptidase 1 (HTRA1) and Interleukin-17 receptor C (IL17RC) together with sFLT1 and maternal age, BMI and nulliparity. Our biomarker signature showed increased or similar predictive performance to the sFLT1/PGF-ratio within our data set, and we were able to validate the biomarker signature in a validation cohort (AUC ≥ 0.90). Further validation of these candidates should be performed using another protein quantification platform in an independent cohort where the negative and positive predictive values can be validly calculated.

Secular variation and risk factors of preterm birth in Hainan, the Free Trade Port in China from 2010 to 2021

ObjectivesPreterm delivery rates have increased obviously worldwide over the past decade, yet reliable epidemiological studies on the incidence of preterm birth and temporal trends are not available in Hainan, The Free Trade Port in China. We aimed to describe the rate of preterm birth and trends between 2010 and 2021 and to primarily explore risk factors associated with preterm birth in Hainan, China.MethodsThis was an observational study was based on data from the Hainan Provincial Birth Certificate System (HPBCS) for live births between 1 January 2010 and 31 December 2021. We included pregnancies resulting in at least one live birth, with newborns born at a gestational age of 28 weeks or greater, or with a birth weight of 1000 g or more. The outcome were preterm birth rates and their trends over time. Potential risk factors were collected, including infant gender, maternal age, paternal age, maternal ethnicity, paternal ethnicity, home address, and single or multiple pregnancies. The logistic regression model was used to assess the relationship between preterm birth and potential risk factors.ResultsA total of 1,537,239 live births and 86,328 preterm births were investigated, giving a total preterm birth rate of 5.62%. The overall preterm birth rate increased from 4.47% in 2010 to 7.12% in 2021 (compound annual growth rate [CAGR] 4.32). The CAGR of late preterm birth is consistent with the overall preterm birth rate (4.32%). The fastest growth is observed in the rate of very preterm births (5.53%), while the rate of moderate preterm births exhibits the slowest growth (3.87%). Infant gender, multiple pregnancy, home address, parental age, and ethnicity had significant effects on preterm birth.ConclusionThe preterm birth rate was increasing year by year from 2010 to 2021 in Hainan, The Free Trade Port in China. Incidence of preterm births in Hainan Province in relation to multiple pregnancies, infant sex, parental age, parental race and residential address.

Food Insecurity and Women's Choice of Reversible Contraceptives: Differential Effects by Maternal Age.

We investigated the relationships between food insecurity (FI) and women's choice of reversible contraceptives, overall and according to the level of method effectiveness, among partnered women of reproductive age in Nigeria. This population-based cross-sectional analysis used nationally representative data from Round 6 of the UNICEF-supported Multiple Indicator Cluster Survey (MICS) conducted in Nigeria. The sample included married or in-union women aged 15-49 years who reported a live birth in the last 2 years preceding the survey (unweighted N = 8496). Survey-weighted multivariable binomial and multinomial logistic regression analyses were performed to generate estimates of the association between FI (none, moderate, and severe) and reversible contraceptive use (overall and by method effectiveness). A Bonferroni correction was used to account for multiple testing. We stratified the models by maternal age to describe the experiences of women aged 15-24 years, 25-34 years, and 35-49 years. Overall, 6438 (74.1%) of the women in the sample experienced food insecurity (moderate, n = 2559, 30.7%; severe, n = 3879, 43.4%). In the adjusted model, we observed no statistically significant association between experiencing MFI and SFI and the use of reversible contraceptives (overall and specific) after adjustment for multiple testing. The stratified analyses showed that among women aged 25-34 years in the sample, those experiencing SFI in the past 12 months, compared to their food-secure counterparts, had significantly lower odds of reporting the use of a least effective contraceptive method (OR, 0.53; 95% CI, 0.34-0.83; p = 0.0052). However, this failed to reach the significance threshold upon adjustment for multiple testing. We found no significant association between the FI levels and use of reversible contraceptives (overall and specific) among partnered women (15-49 years) in Nigeria who were 2 years postpartum following a live birth and who were at risk of pregnancy.

Neonatal Outcomes Following Maternal Antepartum Extracorporeal Life Support.

Cases of antepartum respiratory failure or cardiogenic shock treated successfully with extracorporeal life support (ECLS) with high rates of survival for both mother and fetus are well documented. In contrast, there is a paucity of literature on the outcomes of these neonates after delivery. We report a single-center retrospective study of all adult cases of antepartum ECLS from February 2015 to April 2023 with neonatal follow-up. Seven patients met inclusion criteria with a maternal age of 32.0±5.5 years (median ± interquartile range [IQR]), primarily due to respiratory failure in six (86%) patients, with ECLS initiation at 27.0±3.0 weeks gestation. All mothers and fetuses survived to delivery at a gestational age of 29.0±4.5 weeks. All neonates survived to discharge home with the most common comorbidities being prematurity in seven (100%) patients and bronchopulmonary dysplasia in three (43%). In a follow-up period of 1.4±1.2 years; four (57%) patients underwent formal neurodevelopmental testing and two (50%) had identified delays, both related to speech/language. These results suggest that children exposed to antenatal ECLS demonstrate high rates of survival without significant morbidity, but that follow-up for neurodevelopmental delays may be warranted.

Clinical and epidemiological profiles of newborns from twin pregnancies in Hassan II University Hospital of Fez, Morocco

Twin pregnancies are high-risk pregnancies, and delivery of twins poses variable difficulties due to the complexity of obstetrical mechanics and the frequency of dystocic presentations. Twin births represent a real public health issue and are responsible for a high rate of perinatal mortality. This study aims to report on newborns' epidemiological, clinical, therapeutic, and evolutionary aspects from twin pregnancies hospitalized in the Neonatal Intensive Care and Neonatology Department of the Hassan II University Hospital, Fez. A cross-sectional, retrospective, and descriptive study was conducted on newborns from twin pregnancies hospitalized in the neonatal and neonatal intensive care unit over two and a half years. Statistical analyses were performed using the JAMOVI software. Qualitative variables were expressed as frequencies and percentages, while quantitative variables were presented as means with standard deviations (SD) or medians with interquartile ranges (IQR). A total of 96 newborns from twin pregnancies were collected. The average maternal age was 29.7 years. Maternal complications during pregnancy were dominated by the threat of premature delivery (38.77%), premature rupture of membranes 5.49%), and urinary and cervicovaginal infectious complications (12.24%).89.8% of deliveries were medicalized, with vaginal delivery being the most common (69.39%).91.67% of newborns were premature, thus dominating neonatal morbidity. The average weight was 1585g +/- 425g.76.04% of newborns presented with neonatal respiratory distress, the most frequent etiology of which was hyaline membrane disease. These neonates presented other complications: neonatal jaundice (62.5%), perinatal anoxo-ischemia (6.25%), and transfusion-transfusion syndrome (6.25%). The neonatal mortality rate was 31.25%, with the leading cause being severe neonatal infection (56.67%). The prevalence of twin pregnancies is on the rise, with a high prevalence of prematurity among newborns, requiring special attention to limit complications.

Trends in gestational age at live birth in Scotland from 2005 to 2019: a population-based study.

Gestation at birth is associated with short and long-term outcomes. This study used high quality, national, administrative data to examine trends in gestation at birth in Scotland. This observational study used maternity hospital discharge records for 2005 to 2019 to determine trends in the percentage of live births that were preterm (<37 weeks gestation), term (37-41 weeks), and post-term (≥42 weeks), overall and by maternal age and deprivation category. Preterm births were further examined by category of preterm birth (moderate to late [32-36 weeks]; very [28-31 weeks]; extremely [<28 weeks] preterm), and onset of labour (spontaneous; provider-initiated). Singleton and multiple births were examined separately. Aggregate logistic regression was used to estimate the annual change in the odds of a birth being in a specified gestational category. The percentage of singleton births in Scotland that were preterm decreased from 2005 (6.5%, 3,361/51,665) to 2010 (5.8%, 3268/56344), then increased to 2019 (7.2%, 3,408/47,507). The percentage of singleton births that were spontaneous moderate to late, very, and extremely preterm all increased between 2010 and 2019. The percentage of singleton births that were provider-initiated moderate to late preterm also increased between 2010 and 2019, however provider-initiated very or extremely preterm birth decreased. The percentage of singleton births that were preterm increased over time across all maternal age and deprivation categories, with increases greatest in groups at highest baseline risk. The percentage of singleton births that were post-term increased from 2005 to 2009, then decreased to 2019. There has been an increase in spontaneous preterm birth from 2010 to 2019, which is not fully explained by changes in maternal age or deprivation. Further research to examine the contribution of other, preventable, risk factors is warranted. Trends in provider-initiated preterm birth, and post-term birth, are likely to reflect changing clinical practice.

Analysis of ICAM-1 rs3093030, VCAM-1 rs3783605, and E-Selectin rs1805193 Polymorphisms in African Women Living with HIV and Preeclampsia.

Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms.

Determinants of short birth interval in Ethiopia: A multilevel analysis based on EDHS 2019, Ethiopia, 2023.

According to the World Health Organization and Ethiopian Demographic and Health Survey on birth spacing, there should be at least a two-year gap between conception and the first of two children born in quick succession. In poor nations like Ethiopia, resource issues were complex, making it difficult to get statistics for the entire country. However, by examining Ethiopian mini demographic and health survey data, we were able to provide data at the national level. The cross-sectional survey-based study was conducted in several of Ethiopia's administrative cities and nine regions. In the analysis, sampling weight was used to correct the survey's non-proportional sample distribution to strata and areas throughout the survey process and restore representative data. The study's household population was presented and described using descriptive statistics such as weighted frequencies and percentages. The statistically significant factors linked to frequent short birth intervals were found using a multivariable, multilevel logistic regression analysis. Overall, 4306 weighted multigravida mothers nested within 305 enumeration areas were included in the analysis. The respondents' mean (standard deviation) of the birth interval was 42.027(26.69). Higher-educated women had 12% lower odds of having a shorter pregnancy (AOR = 0.88; 95% CI: 0.35, 0.98) than women without higher education. The odds of a short birth interval were 3.04 times greater among women in the age category of 40-49 years at first marriage (AOR = 3.04; 95% CI: 1.08, 8.46) than among women in the age category of 15-19 years. This indicates that older women were most likely to have short birth intervals. In the multilevel logistic regression model, maternal age, maternal educational status, the wealth quintile index, use of contraceptives, duration of breastfeeding, and contextual regions were significantly associated with short birth intervals in Ethiopia.

Healthcare-seeking behavior for diarrhea in under-five children and associated factors in sub-Saharan Africa: a multilevel robust Poisson regression model.

Diarrhea is one of the leading causes of child death in sub-Saharan Africa (SSA). Children with diarrhea who do not receive medical advice or treatment are at high risk of poor health outcomes and increased mortality. Prompt and adequate treatment is essential to mitigate these risks. However, studies that have been conducted on the factors influencing healthcare-seeking behavior (HSB) for diarrhea in under-five children in SSA are scarce. Therefore, the purpose of this research was to determine the variables related to HSB for diarrhea in children under the age of five. A secondary data analysis was conducted on the most recent data from the Demographic and Health Surveys in 35 SSA countries. The study included a total weighted sample of 51,791 children under the age of five with diarrhea. We presented the adjusted prevalence ratio and the 95% confidence interval in the multivariable multilevel robust Poisson regression analysis to show the statistical significance and strength of the association between HSB and its determinants. The pooled prevalence of HSB for diarrhea in under-five children was 58.71% (95%CI: 55.39 to 62.04). Factors found to be associated with HSB included maternal age, education and working status, antenatal care visits, postnatal checkups for the child, wasting, distance to a health facility, SSA region, and country income level. More than 40% of under-five children with diarrhea in SSA did not receive medical advice or treatment. To improve healthcare-seeking behavior, effective health policy interventions are necessary. These include enhancing the education and employment status of mothers, promoting regular antenatal and postnatal care visits, building health facilities in close proximity, and raising awareness in the community about the importance of seeking healthcare services for malnourished children.

Pre-Conception Androgen Levels and Obstetric Outcomes in Polycystic Ovary Syndrome: A Single-Center Retrospective Study

Hyperandrogenism is a determining diagnostic factor for PCOS. If pregnancy is conceived, it is considered high-risk due to several potential complications, but the correlation between pre-pregnancy androgen levels and obstetric outcomes is poorly characterized. Objective: To determine if pre-pregnancy serum androgen concentrations and androgen indexes differed when certain obstetric and neonatal outcomes appeared in PCOS. Methods: A single-center, retrospective study was carried out. All patients were treated between 2012 and 2019. A total of 73 patients had all the endocrine and obstetric data available. Pre-pregnancy hormone levels (total testosterone-T, androstenedione-AD, DHEAS (dehydroepiandrosterone sulfate), SHBG (sex-hormone-binding globulin), and TSH (thyroid-stimulating hormone) were collected, and T/SHBG, AD/SHBG, DHEAS/SHBG, T/AD indexes were calculated and compared. Results: When miscarriage was present in the history, significantly elevated pre-pregnancy AD levels were observed. Higher pre-pregnancy AD level was noted in PCOS patients delivering female newborns as compared to males. Additionally, a higher T/AD ratio was associated with subsequent preterm delivery, but significance was lost after age adjustment. Maternal age at delivery had a significant negative correlation with pre-pregnancy DHEAS levels and DHEAS/SHBG ratio. Pre-pregnancy SHBG displayed a significant negative correlation, while pre-pregnancy androgen/SHBG ratios exhibited positive correlations with both birth weight and birth weight percentile. Conclusions: Based on our data, AD and the T/AD ratio emerge as distinctive factors in certain outcomes, implying a potential specific role of altered 17-β-HSD (17β-hydroxysteroid dehydrogenase) enzyme activity, possibly influencing offspring outcomes. The pre-pregnancy T/SHBG ratio exhibits a potentially stronger correlation with fetal growth potential compared to SHBG alone. DHEAS and maternal age at delivery are strongly correlated in PCOS patients.

Assessment of Risk Factors Associated with Placenta Previa in a Tertiary Health Institution in Southeast Nigeria

Background: Placenta previa is a significant obstetric complication that can lead to adverse maternal and fetal outcomes. Understanding its risk factors is crucial for early diagnosis and management, particularly in healthcare settings in Nigeria. Objective: To assess the risk factors associated with placenta previa among pregnant women in a tertiary health institution in Southeast Nigeria. Materials and Methods: This prospective descriptive study was conducted over two years (January 2021 to December 2022) and included all pregnant women who delivered in the institution during this period. Data were collected using a structured, interviewer-administered questionnaire after obtaining informed consent from participants. Placenta previa was identified through abdominal ultrasonography, and all confirmed cases were managed according to the MacAfee regimen. Descriptive statistics and chi-square tests were used to analyze the data using SPSS version 26. Results: Out of the 8,766 deliveries recorded in the hospital during the period of this study, 94 (1.07%) were diagnosed with placenta previa. Significant associations were found between placenta previa and factors such as advanced maternal age (≥40 years, p=0.041), history of complications during previous pregnancies (p=0.039), previous cesarean section (p=0.009), history of placenta previa (p&lt;0.001), multiple pregnancies (p=0.001), bleeding during pregnancy (p&lt;0.001), and uterine surgeries apart from cesarean sections (p=0.001). Smoking history was also a significant risk factor (p&lt;0.001). Conclusion: The study identified several risk factors for placenta previa, including advanced maternal age, previous cesarean section, history of placenta previa, multiple pregnancies, uterine surgeries, and smoking. These findings highlight the importance of targeted interventions and close monitoring of at-risk pregnant women to reduce complications.

A Validated Calculator to Estimate Risk of Chorioamnionitis in Laboring and Induced Patients at Term.

Chorioamnionitis is associated with neonatal morbidity and infection-related mortality, but our ability to predict intrapartum infection is limited. We sought to derive and validate a prediction model for chorioamnionitis among patients presenting to labor and delivery at term. This was a planned secondary analysis of a large cohort study from 2014 through 2018 at an academic tertiary care center. To derive a prediction model for chorioamnionitis, we limited our analysis to full-term (≥37 weeks) patients with a singleton gestation undergoing labor induction and presenting in labor. Both nulliparous and multiparous patients were included. Patients with a planned cesarean delivery, fever on admission, or missing data were excluded. The model was derived using multivariable logistic regression. Refinement of the prediction model with internal calibration was performed. External validation was performed utilizing a publicly available database (Consortium on Safe Labor) and applying the same inclusion and exclusion criteria. The discriminative power of each model was assessed using a bootstrap, bias-corrected area under the curve. The chorioamnionitis rates in the derivation and external validation groups were: 5% (1,005/19,966) and 5.8% (n = 3,005/52,171), respectively. In multivariable modeling, maternal age, nulliparity, gestational age, smoking status, group B streptococcus colonization, hours ruptured, number of cervical exams, length of labor, epidural use, internal monitoring, and meconium were significantly associated with infection. A calculator was created and externally validated with an area under the curve of 0.82 (95% confidence interval, 0.81-0.82). External validity was further confirmed with a calibration intercept of 0.81. This is the first infection calculator created and validated for the prediction of developing chorioamnionitis in patients undergoing induction of labor at term. This calculator can be used to augment patient counseling and guide intrapartum infection surveillance in laboring patients.

Incidence of haploidy and triploidy in trophectoderm biopsies of blastocysts derived from normally and abnormally fertilized oocytes.

We aimed to identify the correlation between morphological pronuclear (PN) status and the genetically determined ploidy configuration in preimplantation embryos. A retrospective observational study was conducted on 1982 embryos displaying normal fertilization and 380 embryos showing an atypical PN pattern, tested for aneuploidies and ploidy status via preimplantation genetic testing (PGT) between May 2019 and May 2024. Ploidy prediction was performed using a validated targeted-NGS approach and a proprietary bioinformatic pipeline analyzing SNPs B-allele frequency information. Ploidy results were obtained in relation to the morphological PN pattern and further stratified by mode of PN observation, maternal age, and embryo quality parameters. Abnormal ploidy results in 2PN-derived embryos were 1% (n = 20/1982): 0.8% showed triploidy and 0.2% haploidy. Ploidy results in relation to PN number in atypical fertilization were as follows: 0PN (n = 150/380) associated with 87.3% of diploidy, 8.7% of haploidy, and 4.0% of triploidy; 1PN-derived blastocysts (n = 73/153) were haploid in 47.7% of cases, 6.5% were triploid, and 45.7% diploid; 2.1PN (n = 23/280) and 3PN patterns (n = 54/280) predicted a triploid result in 34.8% and 74.1% of cases, respectively. PN observation with time-lapse increased ploidy status predictivity from 28.3% to 80.4% (p < 0.01) and reduced expected diploid rates to 19.6% (p < 0.01). Diploidy rate was higher for maternal age ≤ 35years and for morphologically high-grade embryos. Morphological PN check can be improved by incorporating ploidy analysis within the conventional PGT workflow. Euploid 2PN-derived embryos can be further selected removing haploids and triploids, and some atypical PN pattern can be better classified.

Validation of Preterm Birth Related Perinatal and Neonatal Data in the Canadian Discharge Abstract Database to Facilitate Long-term Outcomes Research of Individuals Born Preterm

IntroductionThe Canadian Institute of Health Information's (CIHI) Discharge Abstract Database (DAD) contains standardised administrative data on all hospitalisations in Canada, excluding Quebec. ObjectivesWe aimed to validate preterm birth related perinatal and neonatal data in DAD by assessing its accuracy against the reference standard of the Canadian Neonatal Network (CNN) database. MethodsWe linked birth hospitalization data between the DAD and CNN databases for all neonates born $&lt;$33 weeks gestational age (GA) admitted to the Neonatal Intensive Care Units in Winnipeg, Canada, between 2010 and 2022. A comprehensive list of maternal and neonatal variables relevant to preterm birth was chosen \textit{a priori} for validation. For categorical variables, we measured correlation using Cohen's weighted kappa (k) and for continuous variables, we measured agreement using Lin's concordance correlation coefficient (LCCC). Results2084 neonates were included (mean GA 29.4 ± 2.4 weeks; birth weight 1430 ± 461g). Baseline continuous maternal and neonatal variables showed excellent accuracy in DAD [Maternal age: LCCC = 0.99 (0.99, 0.99); GA: LCCC = 0.95 (0.95, 0.96); birth weight: LCCC = 0.97 (0.96, 0.97); sex: k = 0.99 (0.98-0.99)]. In contrast, the accuracy of the maternal baseline categorical variables and neonatal outcomes and interventions ranged from very good to poor [e.g., Caesarean section: k = 0.91 (0.89-0.93), pre-gestational diabetes: k = 0.04 (0.03-0.05), neonatal sepsis: k = 0.37 (0.31-0.42), bronchopulmonary dysplasia: k = 0.26 (0.19-0.33), neonatal laparotomy: k = 0.55 (0.43-067)]. ConclusionNeonatal variables such as gestational age and birth weight had high accuracy in DAD, while the accuracy of maternal and neonatal morbidities and interventions were variable, with some being poor. Reasons for the inaccuracy of these variables should be identified and measures taken to improve them.

MCM proteins are up-regulated in placentas of women with reduced insulin sensitivity.

In the first trimester of pregnancy the human placenta grows rapidly, making it sensitive to changes in the intrauterine environment. To test whether exposure to an environment in utero often associated with obesity modifies placental proteome and function, we performed untargeted proteomics (LC-MS/MS) in placentas from 19 women (gestational age 35-48 days, i.e. 5+0-6+6 weeks). Maternal clinical traits (body mass index, leptin, glucose, C-peptide and insulin sensitivity) and gestational age were recorded. DNA replication and cell cycle pathways were enriched in the proteome of placentas of women with low maternal insulin sensitivity. Driving these pathways were the minichromosome maintenance (MCM) proteins MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7 (MCM-complex). These proteins are part of the pre-replicative complex and participate in DNA damage repair. Indeed, MCM6 and γH2AX (DNA-damage marker) protein levels correlated in first trimester placental tissue (r = 0.514, P<0.01). MCM6 and γH2AX co-localized to nuclei of villous cytotrophoblast cells, the proliferative cell type of the placenta, suggesting increased DNA damage in this cell type. To mimic key features of the intrauterine obesogenic environment, a first trimester trophoblast cell line, i.e., ACH-3P, was exposed to high insulin (10 nM) or low oxygen tension (2.5% O2). There was a significant correlation between MCM6 and γH2AX protein levels, but these were independent of insulin or oxygen exposure. These findings show that chronic exposure in utero to reduced maternal insulin sensitivity during early pregnancy induces changes in the early first trimester placental proteome. Pathways related to DNA replication, cell cycle and DNA damage repair appear especially sensitive to such an in utero environment.

Identifying key predictive features for live birth rate in advanced maternal age patients undergoing single vitrified-warmed blastocyst transfer

BackgroundInfertility affects one in six couples worldwide, with advanced maternal age (AMA) posing unique challenges due to diminished ovarian reserve and reduced oocyte quality. Single vitrified-warmed blastocyst transfer (SVBT) has shown promise in assisted reproductive technology (ART), but success rates in AMA patients remain suboptimal. This study aimed to identify and refine predictive factors for live birth following SVBT in AMA patients, with the goal of enhancing clinical decision-making and enabling personalized treatment strategies.MethodsThis retrospective cohort study analyzed 1,168 SVBT cycles conducted between June 2016 and December 2022 at the First Affiliated Hospital of Guangxi Medical University and Nanning Maternity and Child Health Hospital. Nineteen machine-learning models were applied to identify key predictive factors for live birth. Feature selection and 10-fold cross-validation were employed to validate the models.ResultsThe most significant predictors of live birth included inner cell mass quality, trophectoderm quality, number of oocytes retrieved, endometrial thickness, and the presence of 8-cell blastomeres on day 3. The stacking model demonstrated the best predictive performance (AUC: 0.791), followed by Extra Trees (AUC: 0.784) and Random Forest (AUC: 0.768). These models outperformed traditional methods, achieving superior accuracy, sensitivity, and specificity.ConclusionLeveraging advanced machine-learning models and identifying critical predictive factors can improve the accuracy of live birth outcome predictions for AMA patients undergoing SVBT. These findings offer valuable insights for enhancing clinical decision-making and managing patient expectations. Further research is needed to validate these results in larger, multi-center cohorts and to explore additional factors, including fresh embryo transfers, to broaden the applicability of these models in clinical practice.

Maternal and obstetric outcomes in women with pregnancy-associated haematological malignancies: an observational nationwide cohort study

Pregnancy-associated haematological malignancy is a rare event; therefore, data available to guide the treatment are scarce. We aimed to evaluate the incidence, overall survival, and maternal morbidity and mortality of women with pregnancy-associated haematological malignancies. We conducted a nationwide observational cohort study using the French National Healthcare Data System (SNDS), a health-care administrative database covering up to 99% of the French population. We included all pregnancies in France ending between Jan 1, 2012, and Dec 31, 2022. Pregnancies with terminations or miscarriages managed on an outpatient basis, and women with a history of haematological malignancies before pregnancy were excluded. A Cox proportional hazards model was used to assess overall survival, defined as the date of haematological malignancy diagnosis to either death or the end of the study follow-up, in the haematological malignancy during pregnancy group (pregnancies with a diagnosis of haematological malignancy during pregnancy) compared with the haematological malignancy post-pregnancy group (pregnancies with a diagnosis of haematological malignancy in the year following pregnancy). Severe maternal morbidity was compared in the haematological malignancy during pregnancy group versus the reference group (pregnancies without a history of haematological malignancy or a diagnosis of pregnancy-associated haematological malignancy). Births were classified as very preterm (<32 weeks of pregnancy), preterm (32-36 weeks), and term (≥37 weeks) and compared in the haematological malignancy during pregnancy group versus the reference group. Inverse probability weighting (IPW) was used for confounder adjustment, using maternal age (categorised), comorbidities, socioeconomic status, and year of delivery (as a category). Of 9 996 523 pregnancies in 5 995 235 women, 1366 pregnancy-associated haematological malignancies were identified: 413 during pregnancy (4·13 per 100 000 pregnancies) and 953 (9·53 per 100 000 pregnancies) within 12 months of the end of pregnancy (post-pregnancy). No significant differences in overall survival were observed between the haematological malignancy during and post-pregnancy groups across all types of haematological malignancy (IPW-adjusted hazard ratio 0·91 [95% CI 0·62-1·34], p=0·63), specifically for Hodgkin lymphoma (0·56 [0·07-4·53], p=0·59), aggressive B-cell non-Hodgkin lymphoma (0·52 [0·12-2·38], p=0·40), and acute leukaemia alone (0·84 [0·50-1·41], p=0·51). Severe maternal morbidity was more frequent in the haematological malignancy during pregnancy group than in the reference group (86 [26·2%] of 328 completed pregnancies vs 120 335 [1·5%] of 7 945 909 completed pregnancies; IPW-adjusted odds ratio 22·71 [95% CI 17·72-29·10], p<0·0001). We observed an increase in very preterm birth (32 [9·8%] vs 92 712 [1·2%]; IPW-adjusted odds ratio 11·90 [95% CI 7·91-17·91], p<0·0001) and preterm birth (116 [35·4%] vs 430 472 [5·4%]; 11·76 [9·34-14·81], p<0·0001) in the haematological malignancy during pregnancy group compared with the reference group. This nationwide observational study examines pregnancy-associated haematological malignancies in France, revealing no significant difference in overall survival between women diagnosed during pregnancy and post-pregnancy. Our data highlight an increased frequency of severe maternal morbidity and obstetric complications among women diagnosed during pregnancy. Notably, the study underscores the necessity for specialised care to manage these complex cases effectively. None. For the French translation of the abstract see Supplementary Materials section.

Variables Associated With Favorable Obstetrical Outcomes in Early Pregnancy Bleeding in the Emergency Department.

Background Vaginal bleeding in early pregnancy is a frequent emergency department presentation and is associated with various obstetrical outcomes. Despite this, there has been limited research on the variables that predict less-than-preferred obstetrical outcomes in these cases. This study aims to identify predictors of preferred obstetrical outcomes for women presenting to the emergency department with early pregnancy bleeding. Methods We conducted a retrospective review of health records from an emergency department at a Canadian tertiary care center. Pregnant females presenting with vaginal bleeding before 20 weeks gestation were included. Variables analyzed included maternal age, gravidity, parity, hemoglobin levels, Rh status, cramping, socioeconomic status, and ultrasound findings. The primary outcome was a preferred outcome, defined as a full-term live birth (≥37 weeks). Less-preferred outcomes included miscarriage, preterm birth, and stillbirth. Point-of-care ultrasound and radiology ultrasound findings were also evaluated. Results A total of 422 patients were screened, and 180 were included in the analysis. Overall, 75 (41.7%) patients had a preferred outcome, while 105 (58.3%) had a less-preferred outcome. The strongest predictor of a preferred outcome was the presence of a live intrauterine pregnancy with fetal heartbeat onultrasound, with a preferred outcome rate of 74.5% (56/76) (95% CI 59.8-88.7; p < 0.01) on point-of-care ultrasound (POCUS), and 100% (65/65); p = 0.04 for radiology-performed ultrasound. In contrast, 80.8% (21/26) of patients with findings other than a live intrauterine pregnancy onPOCUS, and 100% (88/88) on radiology-performed ultrasound had a less-preferred outcome. Cramping with bleeding was associated with a higher rate of less-than-preferred outcomes (62.1%, 77/124; 95% CI 54.2-71.1; p = 0.07). Socioeconomic status was not a significant predictor, with similar outcomes above and below the poverty line. Anemia was associated with a 100% non-live birth rate, although only 5 patients were anemic. Conclusion Identification of a live intrauterine pregnancy onultrasound is a strong predictor of a preferred outcome in early pregnancy bleeding. POCUS has the advantage of being immediately available, whereas radiology-performed ultrasound may be more definitive as a predictor. Cramping and anemia may also be associated with less-preferred outcomes, though further research is needed to confirm these findings. These predictors may help guide clinical decision-making and improve counseling for patients presenting to the emergency department with early pregnancy bleeding.

Modern ideas about the predictions of postpartum hemorrhage

Postpartum hemorrhage is currently a pressing problem. Its increasing incidence over time is observed not only in developing countries but also in countries with high levels of income and resources that significantly contribute to the development and functioning of the health system, which is the cause of scientific debate worldwide. The risk factors of postpartum hemorrhage include low hemoglobin level before birth, older maternal age, first birth, prolonged duration of the first and second stages of labor, high birth weight of the newborn, abnormal placentation, surgical vaginal birth, cesarean section, episiotomy, and placental defects. This review outlines the main risk factors of postpartum hemorrhage, displays new data on the relationship between types of assisted reproductive technologies and postpartum hemorrhage, and discusses prospects for research regarding the problem. A link between assisted reproductive technologies and postpartum hemorrhage elucidates the increase in the incidence of postpartum hemorrhage in developed countries. It is crucial to further research on obstetric risks following the use of assisted reproductive technologies and identify additional risk categories for complications to provide quality medical care and reduce maternal and perinatal losses.

Malformaciones congénitas asociadas alSíndrome Down en recién nacidos de un hospitalde referencia nacional: Experiencia de un registrode defectos congénitos

Objective: Down syndrome is the most common chromosomal abnormality in newborns and the first genetic cause of intellectual disability. The objective of this study was to describe associated birth defects with Down syndrome in newborns at the Edgardo Rebagliati MartinsHospital (HNERM). Materials and methods: A descriptive, retrospective and cross-sectionalstudy was conducted. The study population consisted of 191 births diagnosed with Downsyndrome, during the period 2013-2017 of the registry of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) of the HNERM. Results: In the study period, a total of 191 newborns with suspected Down syndrome were reported, of which 180 wereconfirmed with karyotyping, out of a total of 34,326 live births. Free trisomy accounted for98.9%, while mosaicism and translocation trisomy occurred in 0.6% of newborns. The median maternal age was 39 years (range 20-46 years). Congenital heart disease was observed in 61.7%, gastrointestinal malformation 10%, craniofacial malformation 5%, genitourinary 3.9%, musculoskeletal malformation 1.7% and central nervous system malformation 1.7%. Conclusions: The birth prevalence rate of Down syndrome in the study period was 52.4 per 10,000 births. The most frequent malformations associated with Down syndrome are congenital heart disease and secondly malformations of the gastrointestinal tract. Other lessfrequently associated malformations are craniofacial, genitourinary, musculoskeletal and central nervous system malformations.