Retrospective Cohort Study to Investigate Pregnancy Outcomes in a Population of Advanced Maternal Age Congolese Women of Kinshasa: A Study Protocol

Introduction: Pregnancies at advanced maternal age (AMA) are those occurring after the age of 35 years old. They carry a high risk of maternal-fetal morbidity and mortality, thus constituting a public health problem. Several African countries have reported an upward trend in both the age of childbirth and the frequency of women with AMA over the past 20 years. In the Democratic Republic of Congo (DRC), where maternal and neonatal morbidity and mortality remain very high, data on AMA pregnancies go back more than 20 years. Objective: We propose evaluating obstetrical outcomes among women in AMA in our setting and the associated factors. Methods: This retrospective cohort study will be conducted in two healthcare facilities (ESS) in Kinshasa. The study population will consist of all women who delivered a single fetus after 28 weeks of gestation between January 2012 and December 2022 (10 years) in the selected ESS. The data collected will be analyzed using R software version 4.2.0. Quantitative variables will be summarized as means with standard deviation or medians with interquartile range. Qualitative variables will be presented as proportions (%). Multivariate logistic regression will be used to determine the main maternal-fetal complications associated with AMA and predictors of obstetric outcomes. P Discussion: The high maternal and infant mortality rates in DRC are among the highest in the world. The context of maternal age has become a topic of growing interest due to its potential implications for the health of women and newborns, it is crucial to identify the risk factors associated with obstetric outcomes by identifying obstetrical outcomes associated with advanced maternal age in the DRC. Many Congolese women tend to start their maternity journey at a relatively young age. However, there is also an emerging trend towards delayed childbearing, particularly in urban areas and among women with access to education and family planning services. Conclusion: The results of this study will enable us to update the frequency of AMA pregnancies in our environment. The socio-demographic and clinical profile of these pregnancies will be determined. The main maternal-fetal complications associated with AMA in our setting and the associated factors will be identified.

Obstetric Outcomes in Advanced Maternal Age among Women at King Abdulaziz University Hospital

Background: Advanced maternal age, over 35 years, is a well-known risk factor for poor pregnancy outcomes. It is commonly associated with various pregnancy complications, such as spontaneous miscarriage, preeclampsia/ toxemia, gestational diabetes mellitus, preterm labor, stillbirth, chromosomal abnormalities, and cesarean delivery. Objectives: This study assessed obstetric and neonatal complications associated with advanced maternal age. Methods: We reviewed the medical records of 199 pregnant women over 35 years old at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, from January to June 2022. We gathered data on age, nationality, number of antenatal visits, results of ultrasound scans for dating and viability, nuchal translucency and anatomy surveys, medications and multivitamins taken during pregnancy, smoking status, pregnancy, and fetal complications, and mode of delivery. Results: The prevalence of obstetric complications was 71.4% (preeclampsia/toxemia, 4.5%;antepartum hemorrhage, 4%;postpartum hemorrhage, 1%;and gestational diabetes, 23.1%). The most frequent complication was preterm labor between 34 and 36 weeks (48%), and only 12.6% of all deliveries were associated with fetal and neonatal complications such as congenital anomalies and neonatal jaundice. The prevalence of anemia during pregnancy was 10.1%, 21.1%, and 28.6% in the first, second, and third trimesters, respectively, and pregnancies complicated with antepartum or postpartum hemorrhage were associated with higher rates of anemia in the second trimester. A significant relationship was found between mean maternal age (38.84 ± 2.75 years) and the development of maternal complications (p < 0.05). Newborns with neonatal complications were much more likely to be born to mothers with a history of antepartum hemorrhage and anemia in the second trimester. Conclusion: Our findings confirm that pregnancy at an advanced maternal age is associated with increased overall maternal complications. The most frequent complication was preterm labor (48%). Other complications, such as preeclampsia/toxemia, antepartum hemorrhage, postpartum hemorrhage, gestational diabetes, and anemia, were less frequent in the sample we reviewed.

Assisted Hatching in Couples with Advanced Maternal Age： A Systematic Review and Meta-analysis

This systematic review aimed to evaluate the efficacy and safety of assisted hatching （AH） performed in couples with advanced maternal age. We searched for randomized controlled trials （RCTs） in electronic databases, including MEDLINE, EMBASE and CENTRAL （from inception to January 2018）; in addition, we hand-searched the reference lists of included studies and similar reviews. We included RCTs comparing AH versus no treatment （control）. The meta-analysis was performed by RevMan 5.3 software. The search retrieved 943 records and 8 RCTs were included, comprising 870 cycles （n=440 for AH, and n=430 for control）. There was no significant difference in the rates of live birth （RR 0.88, 95% CI 0.65 to 1.18, 3 RCTs, n-427,I^2=0%）, clinical pregnancy （RR 1.00, 95% CI 0.83 to 1.19, 8 RCTs, n=870, I^2=22%）, implantation （RR 1.07, 95% CI 0.83 to 1.39, 4 RCTs, n=1359, I^2=0%）, miscarriage （RR 1.13, 95% CI 0.66 to 1.94, 2 RCTs, n=116, I^2=0%） and multiple pregnancy （RR 0.89, 95% CI 0.31 to 2.52, 1 RCT, n=97,I^2=not applicable） between the treatment group and control group. No reasonable conclusions could be drawn regarding reproductive outcomes after AH in patients with advanced maternal age due to the small sample pooled in meta-analyses. Studies of high methodological quality and with adequate power are necessary to further investigate the value of AH in assisted conception of those patients.

Intrafollicular Soluble RAGE Benefits Embryo Development and Predicts Clinical Pregnancy in Infertile Patients of Advanced Maternal Age Undergoing In Vitro Fertilization

Soluble receptor for advanced glycation end products（s RAGE） can decoy the toxic AGEs and is considered to be a protective factor.This study aimed to evaluate the correlation between intrafollicular s RAGE levels and clinical outcomes in infertile women of young or advanced maternal age（AMA） undergoing in vitro fertilization（IVF）.A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study.The intrafollicular s RAGE concentration was measured to determine its association with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy in young and AMA women,respectively.Besides,correlations between sR AGE and age or follicle-stimulating hormone（FSH） were examined.We found that the intrafollicular s RAGE levels were higher in young patients than those in AMA patients,suggesting that the s RAGE levels were inversely correlated with age.In young patients,sR AGE showed no correlation with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy.But it was found that AMA patients with more retrieved oocytes,fertilized oocytes and high-quality embryos demonstrated higher sR AGE levels,which were a prognostic factor for getting clinical pregnancy independent of age or FSH level.In conclusion,the s RAGE levels decrease with age.Elevated intrafollicular s RAGE levels indicate good follicular growth,fertilization and embryonic development,and successful clinical pregnancy in AMA women,while in young women,the role of s RAGE may not be so predominant.

Maternal Fetal Prognosis: Pregnancy and Delivery in Women of 40 Years Old and Over in a Second Reference Hospital in Bamako

Introduction: Late pregnancies are considered a public health problem linked to maternal mortality due to their complications. These risks, which worsen with maternal age, should be better known and taken into account in monitoring these pregnancies. Objective: To evaluate the impact of age on the prevalence of obstetric and neonatal complications among parturients of 40 years old and over. Methodology: This was an 11-year retrospective analytical case control study from January 1, 2007 to December 31, 2017. The study population was female patients of 40 years old or older for cases and female patients younger than 40 years of control case. Results: In total, we collected 640 cases of parturients of 40 years old and over out of a total of 84,234 deliveries during the study period;i.e. a frequency of 0.76%. Spontaneous abortion increased in patients of 40 and over with 8.28%. Hypertension and diabetes were higher of women of 40 and over, 52.65%. Concerning the method of admission: 55% of parturients of 40 and over were referrals. Incidents occurring among women of 40 and over were more pronounced than in control cases. Complications during vaginal delivery, cervical tear, perineal tear, uterine dehiscence and uterine rupture are high in our cases, i.e. 11.88%;3.59%;2.19%;2.66. During our study, depending on the type of delivery, the cesarean rate was much higher among women of 40 and over than among control cases, i.e. 54.22% versus 12.24%. Hemorrhages in the 3rd trimester were the main indications for cesarean section. Hemorrhages in the 3rd trimester were more frequent with women of 40 and over, i.e. 10.47%;5.94% versus 1.74% and 0.42%. As for the different types of malformations in parturients, women under 40 years old fetal malformations were absent in 92.29%, on the other hand they were more frequent in patients with 40 years and over, i.e. a normal frequency of 36.72%. Conclusion: Pregnancy at a late age exposes the elderly patient and the newborn to several risks. During this study, an increase in maternal-fetal morbidity was observed with aged women.

Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age： a prospective study

Background The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age （AMA）. The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome （DS） and compare the trends of choice of screening and amniocentesis among AMA women. Methods A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010. The gestational weeks were from 15 weeks to 20~6 weeks. The patients referred were grouped into a screening group （2107 cases） and an amniocentesis group （3297 cases） by their own decision. The prevalence of DS was compared between the two groups by chi-square test. Choice rates for each maternal age with trends were compared by regression analysis. Results There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54%o （18/2107）. Twenty- five cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7,58%0 （25/3297）. No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group （P=0.928）. The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group （1/131.88 vs. 1/23.78）. With the increase of the maternal age, the choice of amniocentesis increased while the choice of the screening showed an opposite trend. The choice of the AMA women between the screening and amniocentesis was significantly age relevant （P=0.012）. Conclusions The second trimester serum screening age alone to screen for DS. We suggest educating screening and amniocentesis options. in combination with maternal age was more effective than maternal the patients by recommending AMA women be informed of both

Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level

The mechanisms underlying pregnancy complications caused by advanced maternal age(AMA)remain unclear.We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms.Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing(scRNA-seq).Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications.Trophoblast cells were obtained from the placentas of another six pregnant women(three AMA women and three controls),and in-vitro transwell assays were conducted to observe the cell invasion ability.Thirty additional samples(from 15 AMA women and 15 controls)were analyzed to verify the specific expression of serine protease inhibitor clade E member 1(SERPINE1).Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells.High-quality transcriptomes of 27607 cells were detected.Three types of trophoblast cells were detected,which were further classified into eight subtypes according to differences in gene expression and Gene Ontology(GO)function.We identified 110 differentially expressed genes(DEGs)in trophoblast cells between the AMA and control groups,and the DEGs were enriched in multiple pathways related to cell invasion.In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced.SERPINE1 was specifically expressed in the trophoblast,and its expression was higher in AMA women(P<0.05).Transfection of human SERPINE1(hSERPINE1)into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group.Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women.Abnormal expression of SERPINE1 in extravillous trophoblast(EVT)cells appears to play an important role.

Seizure frequency and obstetric complications at advanced maternal age:a preliminary observational study in women with epilepsy

Background:Seizure control during pregnancy and obstetric outcomes are of important concerns for women with epilepsy(WWE)and their families.Advanced maternal age(≥35 years)shows a growing trend in the society with changes of lifestyle,which also occurs in diseased populations.The advanced maternal age is an independent factor for some unsatisfying obstetric outcomes.In this study we explored the seizure control and obstetric complications associated with advanced maternal age in WWE.Methods:This study was based on the epilepsy pregnancy registry at West China Hospital.Patients with epilepsy in this registry who were aged 35 or older when starting pregnancy were included in this study.Their basic demographics and detailed information on epilepsy management and obstetric issues in all trimesters and during 1-year follow-up after birth were documented and reviewed.Data were processed by IBM SPSS version 22.0.The demographic characteristics,seizure frequency,treatment change,obstetric complications,and outcomes were analyzed and compared.Results:Fifteen patients were included in this study,with an average age of 36.32±2.39 years at pregnancy,and 73.33%of them were primiparas.The change of seizure frequency during pregnancy was not in a clear pattern,but there was an increased incidence of tonic-clonic seizures during the mid-and last trimesters.More than 20%of the patients had obstetric complications throughout the trimesters,including vaginal bleeding,hypothyroidism,and pre-eclampsia.The pre-eclampsia seemed extraordinarily complicated with other conditions.However,none of the complications were related with malformations or poor outcome of babies after 1-year follow-up.Conclusion:Advanced maternal age combined with WWE is associated with frequent common obstetric complications.Future controlled studies with large sample sizes are needed to explore the related risks in comparison with other WWE and non-epileptic populations.

Advanced maternal age and adverse obstetrical and neonatal outcomes of singleton pregnancies

Objective:To assess the impact of advanced maternal age on pregnancy and childbirth outcomes of singleton pregnancies.Study design:We retrospectively assessed singleton pregnant mothers who gave birth at Khaleej-e-Fars Hospital in Bandar Abbas,Iran,from January 2020 to January 2022.Demographic and obstetrical factors include educational level,medical insurance,residency place,access to prenatal care facilities,number of prenatal care visits,smoking status,gestational age,parity,infertility,maternal comorbidities,preeclampsia,eclampsia,preterm birth,low birth weight(LBW),intrauterine growth restriction(IUGR),macrosomia,placenta abnormalities(previa/acreta),placenta abruption,chorioamnionitis,meconium fluid,fetal distress,methods of delivery,rate of cesarean section(CS),perineal lacerations,postpartum hemorrhage,childbirth injury,shoulder dystocia,congenital malformation,neonatal asphyxia,and unfavorable maternal and neonatal outcome were compared between two groups.The Chi-square test assessed the relationship between categorical factors and maternal age groups.The influence of advanced maternal age on the risk of unfavorable pregnancy outcomes was evaluated using bivariate and multivariate logistic regression.Results:Of 8354 singleton deliveries,22.2%belonged to advanced-age mothers.Advanced-age mothers had less education than those aged 20–34 years old.Chronic hypertension,cardiovascular disease,overt diabetes,and thyroid dysfunction were more prevalent among advanced-age mothers.Compared with mothers aged 20–34 years,mothers aged 35 years and higher had a significantly higher risk of gestational diabetes(aOR:3.18,95%CI:1.56–6.95),preeclampsia(aOR:2.91,95%CI:1.35–4.72),placenta abnormalities(aOR:1.09,95%CI:0.77–1.94),CS(aOR:3.16,95%CI:1.51–3.87),postpartum hemorrhage(aOR:1.94,95%CI:1.24–2.61),intensive care unit admission(aOR:1.36,95%CI:1.15–1.99),LBW(aOR:1.35,95%CI:0.97–2.96),preterm birth(aOR:2.36,95%CI:1.65–4.83),stillbirth(aOR:1.18,95%CI:1.01–3.16),and neonatal intensive care admission(aOR:2.09,95%CI:0.73–3.92).According to bivariate regression,the risk of meconium fluid was lower in advanced-age mothers;however,the result of multivariate logistic regression found no correlation between advanced age and the Incidence of meconium fluid.Conclusion:Advanced-age mothers are at increased risk of adverse pregnancy and childbirth outcomes,which persist even after adjusting for several potential confounders.

Effect of maternal age on pregnancy： a retrospective cohort study

Background In the last few decades,there has been a delay in first-time pregnancies,and the average age of women at the time of delivery has increased in many countries.Advanced maternal age is associated with adverse pregnancy outcomes.This study aimed to determine the present trends and pregnancy outcomes related to maternal age in China.Methods Data were collected from 39 hospitals in mainland of China.All deliveries were performed after 28 completed weeks of gestation and between January 1 and December 31,2011.In total,110 450 of 112 441 cases were included in the study.All enrolled cases were divided into 6 age groups with 5-year intervals.The x2 test or Fisher＇s exact test and unadjusted binary-Logistic regression were used for statistical analysis.Results The mean age at the time of delivery was 28.18±4.70 years （range,14-52 years）.The teenage group （15-19 years） had a higher risk than the 25-29-year old group for anemia （odds ratio （OR）,1.4）,preeclampsia （OR,1.6）,preterm birth （OR,2.1）,low birth weight neonates （OR,2.3）,and perinatal mortality （OR,3.6）.The 35-39-year old group and ≥40-year-old group had a higher risk than the 25-29-year-old group for leiomyoma （OR,4.2 vs.5.8）,pregestational diabetes （OR,2.2 vs.3.8）,chronic hypertension （OR,4.6 vs.6.5）,gestational diabetes （OR,2.6 vs.3.5）,preeclampsia （OR,2.5 vs.3.6）,premature delivery （OR,1.8 vs.2.4）,postpartum hemorrhage （OR,1.5 vs.1.7）,placenta previa （OR,2.7 vs.4.0）,placental abruption （OR,1.4 vs.2.5）,cesarean delivery （OR,2.1 vs.2.5）,macrosomia （OR,1.2 vs.1.2）,low birth weight neonates （OR,1.6 vs.2.3）,and perinatal mortality （OR,1.6 vs.3.7）.Conclusion Maternal and neonatal risks are higher during the teenage years and at an advanced maternal age; 20-30 years of age is the lowest risk period for pregnancy and delivery.

Epigenetic changes associated with oocyte aging

It is well established that the decline in female reproductive outcomes is related to postovulatory aging of oocytes and advanced maternal age.Poor oocyte quality is correlated with compromised genetic integrity and epigenetic changes during the oocyte aging process.Here,we review the epigenetic alterations,mainly focused on DNA methylation,histone acetylation and methylation associated with postovulatory oocyte aging as well as advanced maternal age.Furthermore,we address the underlying epigenetic mechanisms that contribute to the decline in oocyte quality during oocyte aging.

Prediction of Cumulative Live Birth Rate in Women Aged 40 Years and Over Undergoing In vitro Fertilization/Intracytoplasmic Sperm Injection

Objective:To investigate cumulative live birth rate (cLBR) per oocyte retrieval in infertile patients aged 40 years and over undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycles and to identify the possible predictors.Methods:A total of 1,613 patients at a university hospital in China from January 2013 to May 2017 were enrolled in this retrospective study.All data for fresh and subsequent frozen-thawed cycles were analyzed.Multivariate logistic regression analysis with stepwise selection of possible predictors for cLBR was performed,and Loess curve was constructed to determine the association between cLBR and the number of oocytes retrieved.Results:cLBR significantly increased with the number of oocytes retrieved and reached up to 75% when > 20 oocytes were retrieved (P<0.001).Variables of antral follicle count (AFC) and the number of oocytes retrieved were selected using multiple logistic regression analysis with stepwise selection to predict the significance of cLBR.cLBR demonstrated an obvious upward trend as the number of oocytes retrieval increased in the Loess curve.Conclusions:For patients aged 40 years and over,AFC and the number of oocytes retrieved were two key predictors for cLBR and maximization of ovarian reserve exploitation was pivotal to increase the chance of live birth.

A Pregnant Woman Died of Sudden Cardiac Death:Should Esophageal Foreign Body Be Considered an Inductive Factor?A Case Report and Literature Review

Here,we report a case of acute attack of coronary heart disease(CHD).A 47‑year‑old pregnant woman with gestational hypertension developed sudden‑onset chest tightness,palpitations,dyspnea,and cyanosis of the face and lips after admission.Her blood pressure was 180/110 mmHg and her blood oxygen saturation was 45%at that time.After cardiopulmonary resuscitation,a weak heartbeat was restored,but oxygen saturation did not increase significantly.Therefore,she was transferred to the intensive care unit;however,she died after 21 days of admission.Autopsy findings revealed that a foreign body was embedded in the esophagus near the right piriform,and her heart weighed 392 g;histopathological examination revealed CHD,thrombosis in the lumen of the right coronary artery,cardiomyocyte hypertrophy,vascular hyaline degeneration in arterioles,neutrophils in the bronchiole and alveolar.All the tested samples yielded negative toxicological results.Clinical status and autopsy findings were not compatible with a diagnosis of peripartum cardiomyopathy.The patient’s sudden death was attributed to CHD,and esophageal foreign‑body impaction was considered to be concomitant phenomenon.Our findings might help in increasing the awareness between esophageal foreign‑body impaction and sudden cardiac death and they can also help in clarifying that understanding the primary cause of death is the key to resolving an iatrogenic medical tangle.