Promising anti-ovarian aging herbal formulation He's Yangchao promotes in vitro maturation of oocytes from advanced maternal age mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Marveled at the discovery of artemisinin, the world's expectations for traditional Chinese medicine are rising. He's Yangchao formula (HSYC) is a traditional Chinese herbal formula with the effects of tonifying kidney and essence, and reconciling yin and yang. It has been clinically proven to have anti-ovarian aging effects. Age is the primary cause of diminished ovarian reserve and assisted reproductive failure in women, whether HSYC has the potential to improve in vitro maturation of oocytes from advanced maternal age (AMA) mice has yet to be determined. AIM OF THE STUDY: This study aims to evaluate the efficacy and possible mechanism of HSYC in promoting in vitro maturation of oocytes from AMA mice. MATERIALS AND METHODS: The GV oocytes were obtained from young and aged mice. The GV oocytes from young mice were cultured in drops of M16 medium, and the GV oocytes from AMA mice were randomly divided four groups: Vehicle group (cultured in 90% M16 medium +10% blank serum), Low HSYC group (cultured in 90% M16 medium + 10% Low HSYC-medicated serum), High-HSYC group (cultured in 90% M16 medium +10% High HSYC-medicated serum), and Quercetin group (cultured in M16 medium supplemented with 10 µM quercetin). The rates of first polar body extrusion, reactive oxygen species (ROS), intracellular calcium, and mitochondrial membrane potential levels in each groups were observed. In addition, expression levels of mitochondrial function, autophagy, DNA damage, and antioxidant-related proteins were assessed. RESULTS: Supplementation of HSYC in vitro alleviated age-associated meiotic progression defects in maternally aged oocytes. Importantly, HSYC supplementation eliminated the age-related ROS accumulation to suppress DNA damage and autophagy during the in vitro maturation of maternally aged oocytes. Meanwhile, the mitochondrial function was improved after HSYC treatment, as manifested by higher mitochondrial membrane potential and lower Ca2+ levels. Furthermore, we found that HSYC supplementation during in vitro maturation of maternally aged oocytes upregulated the expression level of SIRT3, a crucial protein in regulating mitochondrial function. Consistently, the expression levels of the SOD2, PCG1α, and TFAM were increased, while the SOD2 acetylation level was decreased, which further proved its antioxidant function. CONCLUSIONS: HSYC supplementation promotes in vitro maturation of oocytes from AMA mice mainly via improving mitochondrial function and alleviating oxidative stress. The mechanism may be related to the regulation of SIRT3-dependent deacetylation of the SOD2 pathway.

A study of application effects of next-generation sequencing based preimplantation genetic testing for aneuploidies in advanced maternal age women.

OBJECTIVE: To investigate if next-generation sequencing-based preimplantation genetic testing for aneuploidies could improve pregnancy outcomes in women of advanced maternal age. MATERIALS AND METHODS: A retrospective analysis. The clinical data of 1099 couples treated in the First Medical Center of the Chinese PLA General Hospital from January 2019 to December 2021 were analyzed. They were divided into two groups based on whether they underwent a Next-generation sequencing-based preimplantation genetic test for aneuploidies. We analyzed and compared the biochemical pregnancy rate, clinical pregnancy rate, abortion rate, and live birth rate between the two groups. RESULTS: The Preimplantation genetic testing for aneuploidies (PGT-A) group was associated with higher rate of biochemical pregnancy and clinical pregnancy than the non-PGT-A group, which were 63.9% vs. 56.4% (P = 0.009) and 54.4% vs. 45.6% (P < 0.001), respectively. The abortion rate was significantly lower in the PGT-A group compared to the non-PGT-A group (2.3% vs. 14.7%, P < 0.001). In addition, the live birth rate was significantly higher in the PGT-A group compared to the non-PGT-A group (52.1% and 30.9%, respectively, P < 0.001). CONCLUSION: Next-generation sequencing-based preimplantation genetic testing for aneuploidies significantly improved the pregnancy outcomes in women of advanced maternal age.

High maternal mortality rate associated with advanced maternal age in Japan.

This study aimed to clarify the relationship between maternal mortality and advanced maternal age in Japan and to provide useful information for future perinatal management. Maternal death rates by age group were investigated for all maternal deaths in Japan for an 11-year period, from 2010 to 2021. Maternal deaths among those aged ≥ 40 years were examined in detail to determine the cause, and the number of deaths by cause was calculated. The causes of onset of the most common causes of death were also investigated. The maternal mortality rates were 0.8 (95% confidence interval [CI] 0.3-4.7) for < 20 years, 2.6 (95% CI 1.7-3.8) for 20-24 years, 2.9 (95% CI 2.3-3.6) for 25-29 years, 3.9 (95% CI 3.3-4.5) for 30-34 years, 6.8 (95% CI 5.9-7.9) for 35-39 years, and 11.2 (95% CI 8.8-14.3) for ≥ 40 years of age. Patients who were ≥ 40 years of age had a significantly higher mortality rate compared to that in other age groups. Hemorrhagic stroke was the most common cause of death in patients aged ≥ 40 years (15/65 [23%]), and preeclampsia (8/15 [54%]) was the most common cause of hemorrhagic stroke. Maternal mortality is significantly higher in older than in younger pregnant women in Japan, with hemorrhagic stroke being the most common cause of maternal death among women > 40 years of age. More than half of hemorrhagic strokes are associated with hypertension disorder of pregnancy. These facts should be considered by women who become pregnant at an advanced age and by healthcare providers involved in their perinatal care.

Development of a prediction model for neonatal hypoglycemia risk factors: a retrospective study.

Background: It's challenging for healthcare workers to detect neonatal hypoglycemia due to its rapid progression and lack of aura symptoms. This may lead to brain function impairment for the newborn, placing a significant care burden on the family and creating an economic burden for society. Tools for early diagnosis of neonatal hypoglycemia are lacking. This study aimed to identify newborns at high risk of developing neonatal hypoglycemia early by developing a risk prediction model. Methods: Using a retrospective design, pairs (470) of women and their newborns in a tertiary hospital from December 2021 to September 2022 were included in this study. Socio-demographic data and clinical data of mothers and newborns were collected. Univariate and multivariate logistic regression were used to screen optimized factors. A neonatal hypoglycemia risk nomogram was constructed using R software, and the calibration curve and receiver operator characteristic curve (ROC) was utilized to evaluate model performance. Results: Factors integrated into the prediction risk nomogram were maternal age (odds ratio [OR] =1.10, 95% CI: 1.04, 1.17), fasting period (OR=1.07, 95% CI: 1.03, 1.12), ritodrine use (OR=2.00, 95% CI: 1.05, 3.88), gestational diabetes mellitus (OR=2.13, 95% CI: 1.30, 3.50), gestational week (OR=0.80, 95% CI: 0.66, 0.96), fetal distress (OR=1.76, 95% CI: 1.11, 2.79) and neonatal body mass index (OR=1.50, 95% CI: 1.24, 1.84). The area under the curve (AUC) was 0.79 (95% confidence interval [CI]: 0.75, 0.82), specificity was 0.82, and sensitivity was 0.62. Conclusion: The prediction model of this study demonstrated good predictive performance. The development of the model identifies advancing maternal age, an extended fasting period before delivery, ritodrine use, gestational diabetes mellitus diagnosis, fetal distress diagnosis and an increase in neonatal body mass index increase the probability of developing neonatal hypoglycemia, while an extended gestational week reduces the probability of developing neonatal hypoglycemia.

Analysis of the results of non-invasive prenatal testing (NIPT) in 545 pregnant women in advanced maternal age.

OBJECTIVE: This research aimed to explore the value of non-invasive prenatal testing (NIPT) as a prenatal screening method for common aneuploidy in pregnant women in advanced maternal age. PATIENTS AND METHODS: A retrospective analysis was conducted on a cohort of 545 mothers with singleton pregnancy who were of advanced age and underwent NIPT testing voluntarily at the Second Affiliated Hospital of Guangxi Medical University between November 2020 and February 2023. In cases where NIPT testing suggested chromosomal abnormalities, amniocentesis was conducted, karyotype analysis or gene copy number variation (CNV) testing was performed, and the pregnancy outcome was tracked. RESULTS: Among 545 pregnant women in advanced maternal age, 11 cases had high risk of NIPT, and the detection rate was 2.02%. Among 11 pregnant women deemed to be at high risk for NIPT, 10 cases underwent amniotic fluid puncture, and one case refused amniocentesis despite a suggestive chromosomal abnormality in NIPT. The overall rate of amniocentesis was 1.83%. Among 11 pregnant women deemed to be at high risk for NIPT, the results suggested that 5 of them had trisomy 21, 1 had trisomy 18, 2 had sex chromosome abnormalities (specifically, 47, XYY), and 3 had other autosomal abnormalities. The positive predictive values of NIPT were 100.00% for the cases of trisomy 21 and trisomy 18, while the values were 0.00% for the cases of sex chromosome abnormalities and other autosomal abnormalities, respectively. After the follow-up, each of the 6 cases that were diagnosed with definite chromosomal abnormalities during prenatal screening opted to induce labor and terminate the pregnancy, including 5 cases that exhibited a high risk of trisomy 21 (47, XN,+21) and 1 case that showed a high risk of trisomy 18 (47, XN,+18). One instance of NIPT indicated a potential abnormality in the sex chromosomes, the individual declined to undergo amniocentesis. Another instance of NIPT suggested a sex chromosome abnormality, amniocentesis revealed a deletion of 0.72 Mb in the 4q22.1 region. They all had normal pregnancies and normal newborns. The remaining three cases had normal prenatal diagnoses (46, XN) and experienced normal pregnancies with healthy neonatal outcomes. CONCLUSIONS: NIPT has demonstrated its efficacy as a screening tool in the face of increasing maternal age. As a result, it can substantially decrease the requirement for invasive prenatal diagnosis. Nonetheless, there are instances of erroneous positive outcomes in NIPT testing, and therefore, interventional prenatal diagnosis remains necessary for individuals with high-risk screening outcomes to prevent false positives or unwarranted labor induction.

The role of maternal age on adverse pregnancy outcomes among primiparous women with singleton birth: a retrospective cohort study in urban areas of China.

BACKGROUND: Both young and advanced maternal age pregnancies have strong associations with adverse pregnancy outcomes; however, there is limited understanding of how these associations present in an urban environment in China. This study aimed to analyze the associations between maternal age and pregnancy outcomes among Chinese urban women. METHODS: We performed a population-based study consisting of 60,209 singleton pregnancies of primiparous women whose newborns were delivered after 20 weeks' gestation between January 2012 and December 2015 in urban areas of China. Participants were divided into six groups (19 or younger, 20-24, 25-29, 30-34, 35-39, 40 or older). Pregnancy outcomes include gestational diabetes mellitus (GDM), preeclampsia, placental abruption, placenta previa, premature rupture of membrane (PROM), postpartum hemorrhage, preterm birth, low birthweight, small for gestational age (SGA), large for gestational age (LGA), fetal distress, congenital microtia, and fetal death. Logistic regression models were used to assess the role of maternal age on the risk of adverse pregnancy outcomes with women aged 25-29 years as the reference group. RESULTS: The risks of GDM, preeclampsia, placenta previa, and postpartum hemorrhage were decreased for women at a young maternal age and increased for women with advanced maternal age. Both young and advanced maternal age increased the risk of preterm birth and low birthweight. Young maternal age was also associated with increased risk of SGA (aOR 1.64, 95% CI 1.46-1.83) and fetal death (aOR 2.08, 95% CI 1.35-3.20). Maternal age over 40 years elevated the odds of placental abruption (aOR 3.44, 95% CI 1.47-8.03), LGA (aOR 1.47, 95% CI 1.09-1.98), fetal death (aOR 2.67, 95% CI 1.16-6.14), and congenital microtia (aOR 13.92, 95% CI 3.91-49.57). There were positive linear associations between maternal age and GDM, preeclampsia, placental abruption, placenta previa, PROM, postpartum hemorrhage, preterm birth, LGA and fetal distress (all P for linear trend < .05), and a negative linear association between maternal age and SGA (P for linear trend < .001). The analysis of the associations between maternal age and adverse fetal outcomes showed U-shape for preterm birth, low birth weight, SGA, fetal death and congenital microtia (all P for quadratic trend < .001). CONCLUSIONS: Advanced maternal age predisposes women to adverse obstetric outcomes. Young maternal age manifests a bidirectional effect on adverse pregnancy outcomes. The findings may contribute to improving women's antenatal care and management.

Murine models of advanced maternal age: a systematic review and meta-analysis.

In brief: Animal models have been developed to aid understanding of the increased incidence of adverse pregnancy complications observed in women of advanced maternal age (AMA). This systematic review of murine models of AMA demonstrates consistent effects of decreased litter size and fetal weight; this supports the future use of these models to determine pathophysiological mechanisms and test therapeutic strategies to improve poor pregnancy outcomes in AMA. Abstract: Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcomes in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcomes. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcomes in AMA mice and rats were included; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool evaluated the risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (standardised mean difference (SMD): -1.59, 95% confidence interval (CI): -1.84, -1.34 for mice; SMD: -1.66, 95% (CI): -2.09, -1.23 for rats) and reduced fetal weight (SMD: -0.87, 95% CI: -1.24, -0.49 for mice; SMD: -1.05, 95% CI: -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD: 0.62, 95% CI: 0.16, 1.08). Subgroup analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2 = 68.2% vs other strain types I2 = 85.7%). The risk of bias was high, mostly due to the lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow the exploration of mechanisms underpinning poor pregnancy outcomes and the pursuit of therapeutic interventions.

Transcriptomic profiling of human granulosa cells between women with advanced maternal age with different ovarian reserve.

BACKGROUND: Age-related diminished ovarian reserve (DOR) is not absolute. Some advanced maternal age (AMA) still have normal ovarian reserve (NOR) and often show better pregnancy outcomes. Exploring the transcriptomic profile of granulosa cells (GCs) in AMA could lead to new ideas for mitigating age-related diminished ovarian reserve. AIM: This study aimed to analyze the transcriptomic profile of GCs in AMA with different ovarian reserve. RESULTS: In total, 6273 statistically significant differential expression genes (DEGs) (|log2fc|> 1, q < 0.05) were screened from the two groups, among which 3436 genes were upregulated, and 2837 genes were downregulated in the DOR group. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the potential functions of dysregulated genes in AMA with DOR or NOR were predicted. The GO enrichment analysis revealed that the DEGs were mainly enriched in obsolete oxidation-reduction process, mitochondrion, metal ion binding, ATP binding, etc. The KEGG pathway enrichment analysis revealed that the above-mentioned DEGs were mainly enriched in ferroptosis, regulation of actin cytoskeleton, oxidative phosphorylation, etc. Meanwhile, verification of the mRNA expression levels of DEGs revealed the possible involvement of "ferroptosis" in age-related diminished ovarian reserve. CONCLUSIONS: From a new clinical perspective, we presented the first data showing the transcriptomic profile in GCs between AMA with different ovarian reserve. At the same time, we identified the role of ferroptosis in the GCs of AMA, providing a new biological basis for studying ovarian aging and improving pregnancy outcomes of AMA.

Dose-related relationship between ergothioneine concentrations and risk of preeclampsia.

The study by Kenny et al. is of considerable importance. They concluded that there was a weak association between the ergothioneine levels and maternal age, and if a threshold was set at the 90th percentile of the reference range in the control population (≥462 ng/ml), only one of these 97 women (1%) developed preeclampsia, versus 96/397 (24.2%) whose ergothioneine level was below this threshold. These results suggest that there might be a dichotomized association between ergothioneine concentrations and preeclampsia; and only a high ergothioneine level over 90th percentile of the control population could be protective against preeclampsia. With the kind supply of the dataset from the authors, further analysis using univariable as well as multivariable analyses were performed while allowing for non-linearity between ergothioneine concentrations and risk of preeclampsia using a 3-knot restricted cubic spline function. The univariable results showed that ergothioneine had a significant non-linear association with preeclampsia and it would start to offer protective effect from 300 ng/ml onward. The results were similar to the multivariable analysis. In addition, the analysis also confirmed that body mass index was significantly associated with an increased risk of preeclampsia.

Association between cell-free DNA fetal fraction and pregnant character: a retrospective cohort study of 27,793 maternal plasmas.

To determine the association between cell-free DNA fetal fraction (cffDNA) and various prenatal characters to better guide the clinical application of noninvasive prenatal screening (NIPS), a retrospective cohort study of 27,793 women with singleton pregnancies was conducted. Results indicated that no significant difference on cffDNA between trisomy/sex chromosome aneuploidy (SCA) and non-trisomy groups was found. However, the fetal fraction (FF) in the T18 and T13 subgroups were significantly lower than that in the non-trisomy group, while the FF in the T21 group was significantly higher than the non-trisomy group. Pearson's correlation analysis revealed a positive correlation between √FF and gestational week in the T21, SCA, and non-trisomy groups. A negative correlation between maternal age and √FF in T21 and non-trisomy cases was found, but a positive correlation in SCA group. Compared to the decreasing trend in FF in the T21 group, no significant difference was observed in the SCA group. The √FF level was negatively correlated to maternal BMI in T21 and non-trisomy group, while a positive correlation in SCA group. FF was close related to the result of NIPS and related maternal factors. Though NIPS has increased accuracy, the complexity still should be recognized especially in clinical practice.

Pregnancy complications in last pregnancy and mothers' long-term cardiovascular mortality: does the relation differ from that of complications in first pregnancy? A population-based study.

BACKGROUND: Women who experience complications in first pregnancy are at increased risk of cardiovascular disease (CVD) later in life. Little corresponding knowledge is available for complications in later pregnancies. Therefore, we assessed complications (preeclampsia, preterm birth, and offspring small for gestational age) in first and last pregnancies and the risk of long-term maternal CVD death, taking women´s complete reproduction into account. DATA AND METHODS: We linked data from the Medical Birth Registry of Norway to the national Cause of Death Registry. We followed women whose first birth took place during 1967-2013, from the date of their last birth until death, or December 31st 2020, whichever occurred first. We analysed risk of CVD death until 69 years of age according to any complications in last pregnancy. Using Cox regression analysis, we adjusted for maternal age at first birth and level of education. RESULTS: Women with any complications in their last or first pregnancy were at higher risk of CVD death than mothers with two-lifetime births and no pregnancy complications (reference). For example, the adjusted hazard ratio (aHR) for women with four births and any complications only in the last pregnancy was 2.85 (95% CI, 1.93-4.20). If a complication occurred in the first pregnancy only, the aHR was 1.74 (1.24-2.45). Corresponding hazard ratios for women with two births were 1.82 (CI, 1.59-2.08) and 1.41 (1.26-1.58), respectively. CONCLUSIONS: The risk for CVD death was higher among mothers with complications only in their last pregnancy compared to women with no complications, and also higher compared to mothers with a complication only in their first pregnancy.

Child marriage in rural Bangladesh and impact on obstetric complications and perinatal death: Findings from a health and demographic surveillance system.

Adolescent pregnancies, a risk factor for obstetric complications and perinatal mortality, are driven by child marriage in many regions of South Asia. We used data collected between 2017-2019 from 56,155 married adolescents and women in a health and demographic surveillance system to present a population-level description of historical trends in child marriage from 1990-2019 as well as epidemiologic associations between maternal age and pregnancy outcomes in Baliakandi, a rural sub-district of Bangladesh. For pregnancies identified between 2017-2019, we used Kaplan-Meier estimates to examine timing of first pregnancies after first marriage and multinomial logistic regression to estimate associations between maternal age and perinatal death. We described the frequency of self-reported obstetric complications at labor and delivery by maternal age. In 1990, 71% of all marriages were to female residents under 18 years of age. This decreased to 57% in 2010, with the largest reduction among females aged 10-12 years (22% to 3%), and to 53% in 2019. Half of all newly married females were pregnant within a year of marriage, including adolescent brides. Although we observed a decline in child marriages since 1990, over half of all marriages in 2019 were to child brides in Baliakandi. In this same population, adolescent pregnancies were more likely to result in obstetric complications (13-15 years: 36%, 16-17 years: 32%, 18-34 years: 23%; χ2 test, p<0.001) and perinatal deaths (13-15 years: stillbirth OR 2.23, 95% CI 1.01-2.42; 16-17 years: early neonatal death OR 1.57, 95% CI: 1.01-2.42) compared to adult pregnancies. Preventing child marriage can improve the health of girls and contribute to Bangladesh's commitment to reducing child mortality.

Influence of maternal age on the birthweight of infants delivered from frozen-thawed blastocyst transfer cycles.

The aim of this study was to investigate whether maternal age had an effect on the birthweight of singletons delivered from frozen-thawed blastocyst transfer (FBT) cycles. A total of 1203 FBT cycles occurring between July 2011 and June 2021 at a single centre were retrospectively analysed. Based on the maternal age at FBT, the patients were divided into four groups: <30, 30-34, 35-37, and ≥38 years of age. Main outcomes measured included singleton birthweights, preterm births, large-for-gestational-age (LGA) and small-for-gestational-age (SGA) live births among the groups. There was no significant difference in birth weight among the four groups, while the highest birth weight was found in the <30 years group. The incidence of very preterm births and very low birth weights demonstrated an increasing trend with age; on the contrary, the incidence of preterm births, low birth weight (LBW), high birth weight and LGA and SGA live births gradually decreased with increasing age, but these differences were not statistically significant among groups (P>0.05, respectively). Although the proportion of females was lower than that of males, the difference was not statistically significant among the groups. After adjusting for possible confounders, maternal age was found to have no effect on adverse neonatal outcomes in the regression analyses (P>0.05). Birthweight in singleton births from FBT was not affected by maternal age.

A systematic review on maternal and perinatal factors influencing breast development.

BACKGROUND: A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship between in utero and early life events and breast onset/development. METHODS: Eligible studies were identified in PubMed and Embase databases. We selected studies in which female human exposure during fetal or the first years of life was measured or estimated, and associations with breast onset or development were evaluated. RESULTS: Of the 49 cohort studies and 5 cross-sectional studies identified, 43 provided sufficient data to assess associations. High maternal weight, primiparity, and early weight gain, were related to an increased risk of early breast onset/development in most of the studies that analysed these associations, whereas late breast onset/development was associated with preterm birth. Results were inconsistent for smoking in pregnancy, maternal hypertensive disorders, breastfeeding, diabetes, and small for gestational age. No association emerged for maternal age at delivery, alcohol drinking, and selected drug use during pregnancy, and low birth weight. CONCLUSIONS: The results of this review show that high maternal weight, primiparity and early weight gain were associated with an increased risk of early breast onset/development. Late breast onset/development was associated with preterm birth. Breast development is a key physical marker of puberty onset, and early puberty development is linked to consequences that can reverberate throughout life. Answering the questions about the interconnections between pre/postnatal environmental exposures and their impact on puberty, represents an important area of multidisciplinary research.

The Vaginal Microbiota of Pregnant Women Varies with Gestational Age, Maternal Age, and Parity.

The composition of the vaginal microbiota is heavily influenced by pregnancy and may factor into pregnancy complications, including spontaneous preterm birth. However, results among studies have been inconsistent due, in part, to variation in sample sizes and ethnicity. Thus, an association between the vaginal microbiota and preterm labor continues to be debated. Yet, before assessing associations between the composition of the vaginal microbiota and preterm labor, a robust and in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required. Here, we report a large longitudinal study (n = 474 women, 1,862 vaginal samples) of a predominantly African-American cohort-a population that experiences a relatively high rate of pregnancy complications-evaluating associations between individual identity, gestational age, and other maternal characteristics with the composition of the vaginal microbiota throughout gestation resulting in term delivery. The principal factors influencing the composition of the vaginal microbiota in pregnancy are individual identity and gestational age at sampling. Other factors are maternal age, parity, obesity, and self-reported Cannabis use. The general pattern across gestation is for the vaginal microbiota to remain or transition to a state of Lactobacillus dominance. This pattern can be modified by maternal parity and obesity. Regardless, network analyses reveal dynamic associations among specific bacterial taxa within the vaginal ecosystem, which shift throughout the course of pregnancy. This study provides a robust foundational understanding of the vaginal microbiota in pregnancy and sets the stage for further investigation of this microbiota in obstetrical disease. IMPORTANCE There is debate regarding links between the vaginal microbiota and pregnancy complications, especially spontaneous preterm birth. Inconsistencies in results among studies are likely due to differences in sample sizes and cohort ethnicity. Ethnicity is a complicating factor because, although all bacterial taxa commonly inhabiting the vagina are present among all ethnicities, the frequencies of these taxa vary among ethnicities. Therefore, an in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required prior to evaluating associations between the vaginal microbiota and obstetrical disease. This initial investigation is a large longitudinal study of the vaginal microbiota throughout gestation resulting in a term delivery in a predominantly African-American cohort, a population that experiences disproportionally negative maternal-fetal health outcomes. It establishes the magnitude of associations between maternal characteristics, such as age, parity, body mass index, and self-reported Cannabis use, on the vaginal microbiota in pregnancy.

Survey assessing policies regarding patient age and provision of fertility treatment in the United States.

PURPOSE: To determine what policies exist regarding age and provision of fertility treatment in United States fertility clinics. METHODS: Medical directors of the Society for Assisted Reproductive Technology (SART) member clinics were surveyed regarding clinic demographics and current policies pertaining to age and provision of fertility treatment. Univariate comparisons were performed using Chi-square and Fisher exact tests as appropriate, with significance set at P ≤ 0.05. RESULTS: Of the 366 clinics surveyed, 18.9% (69/366) responded. A majority of clinics who responded 88.4% (61/69) reported having a policy regarding patient age and provision of fertility treatment. Responding clinics with an age policy did not differ from those without a policy on the basis of geographical location, (p = 0.5), insurance mandate status (p = 0.9), practice type (p = 0.4), or annual number of ART cycles (p = 0.7). Of all clinics who responded, 73.9% (51/69) had a maximum maternal age for autologous IVF, with a median of 45 years (range 42-54). Similarly, 79.7% (55/69) of responding clinics had a maximum maternal age for donor oocyte IVF, with a median of 52 years (range 48-56). Slightly under half, 43.4% (30/69) of responding clinics had a maximum maternal age for fertility treatment other than IVF (including ovulation induction or ovarian stimulation with or without IUI) with a median of 46 years (range 42-55). Of note, only 4.3% (3/69) of responding clinics had a policy with respect to maximum paternal age, with a median of 55 years (range 55-70). The most commonly cited reasons for having an age-limit policy were maternal risks of pregnancy, lower ART success rates, fetal/neonatal risks, and concerns about patients' ability to parent at an older age. More than half 56.5% (39/69) of responding clinics reported making exceptions to these policies, most commonly for patients who have pre-existing embryos. The majority of medical directors who responded to the survey believed there should be an ASRM guideline regarding maximum maternal age for autologous IVF 71% (49/69), donor oocyte IVF 78% (54/69) and other fertility treatments 62% (43/69). CONCLUSIONS: Most fertility clinics who responded to this national survey reported having a policy regarding maternal age (but not paternal age) and provision of fertility treatment. Policies were based on risk of maternal/fetal complications, lower success rates at older age, and concerns about patients' ability to parent at an older age. The majority of medical directors of responding clinics believed there should be an ASRM guideline regarding age and provision of fertility treatment.

Role of Maternal Age in Increasing Severe Maternal Morbidity Rates in the United States.

OBJECTIVE: To evaluate a commonly proposed explanation for increasing rates of severe maternal morbidity (SMM) in the United States: shifts in the birthing population to older maternal ages, a known risk factor for SMM. METHODS: We conducted a cross-sectional analysis comparing delivery hospitalizations from two time points (2008-2009 to 2017-2018) using hospital discharge data from the National Inpatient Sample. We used demographic decomposition techniques to evaluate whether increasing rates of SMM and nontransfusion SMM were explained by population-level increases in maternal age or changes in age-specific rates. Analyses were stratified by race and ethnicity. RESULTS: Rates of SMM and nontransfusion SMM significantly increased in the United States between 2008 and 2018 from 135.6 to 170.5 and 58.8 to 67.9 per 10,000 delivery hospitalizations, respectively, with increases observed for nearly all racial and ethnic groups. Over this same period, the proportion of births to people younger than age 25 years decreased and births to people of advanced maternal age (35 years and older) increased, with the largest increases occurring among people identified as non-Hispanic American Indian/Alaskan Native (9.8-13.0%), non-Hispanic Black (10.7-14.4%), and Hispanic (12.1-17.1%). Decomposition analyses indicated that the changing maternal age distribution had little effect on SMM trends. Rather, increases in SMM and nontransfusion SMM were primarily driven by increases in age-specific SMM rates, including rising rates among younger people. Contributions of maternal age shifts were minimal for all racial and ethnic groups except among non-Hispanic Black people, for which 17-34% of the rise in SMM was due to increasing maternal age. CONCLUSION: Except among certain racial groups, increases in U.S. population-level SMM rates over the past decade were due to increases in age-specific rates rather than shifts to older maternal age among the birthing population. Increasing SMM rates across the maternal age spectrum could indicate worsening prepregnancy health status of the birthing population.

Investigation of Igf-1, Igf-Bp3 and Igf-Bp5 levels in umbilical cord blood of infants with developmental dysplasia of the hip.

BACKGROUND: IGF-1 (insulin-like growth factor-1) is an important regulator of bone formation. Its deficiency has been associated with fetal growth disorders and hip dysplasia. The aim of this study was to evaluate whether IGF-1, IGF-BP3 (insulin like growth factorbinding protein 3), and IGF-BP5 levels in the umbilical cord blood can be predictive for early diagnosis of DDH. METHODS: Umbilical cord blood samples were collected from 860 mothers with pregnancies at high risk for DDH between October 2020 and January 2021. Mothers at 37-42 weeks of gestation, with risk factors for DDH, who delivered healthy infants were included. Blood samples were collected during delivery. Each eligible infant was medically followed up and underwent a hip ultrasound in the postnatal 2nd or 3rd month. Infants diagnosed with DDH were matched with a healthy cohort in terms of sex, birth weight, maternal age, and gestational week, and the IGF-1, IGF-BP3 and IGF-BP5 levels were studied and compared. RESULTS: Evaluation was made of 20 infants diagnosed with DDH and 60 healthy infants. Of the total 80 infants, 72.5% were female.The umbilical cord blood levels of IGF-1 and IGF-BP3 were similar in both groups. The IGF-BP5 values were significantly lower in the DDH patient group. Except for DDH diagnosis, the other categorical variables of the study did not appear to influence the levels of any of the IGFs. DISCUSSION: Umbilical blood samples could potentially help diagnose DDH. The levels of IGF-BP5 were shown to be significantly lower in infants with DDH.

The modest impact of assisted reproductive technology on the second birth: insights from a population-based study in Lombardy, Northern Italy.

BACKGROUND: In the field of assisted reproductive technology (ART), family rate is a neglected but emerging issue. The aim of the study was to investigate the epidemiological impact of ART on the second birth during the period 2007-2020 in Lombardy, Northern Italy. METHODS: We conducted a population-based study using administrative data from regional healthcare databases of Lombardy including first and second births occurred from 2007 to 2020. The proportion of deliveries after ART was calculated separately among first and second births. The probability of undergoing ART to achieve second birth compared to first one was estimated computing odds ratio (OR), crude and adjusted for maternal age, education, and nationality. We also assessed changes with age and calendar period. RESULTS: We obtained a cohort including 553,190 first births and 317,976 second births. The proportion of ART babies among first and second births was 4.3% and 1.0% respectively (p < 0.001). The probability of undergoing ART to achieve second birth compared to first one, adjusted for age, education, and nationality, was 0.14 (95%CI: 0.13-0.15). The proportion of deliveries after ART increased with maternal age and along the calendar period but remained always markedly higher among first births rather than among second births. CONCLUSION: ART played a significantly lower role in the determinism of the conception of a second birth in comparison to the conception of a first one.

Pathogenic copy number variations are associated with foetal short femur length in a tertiary referral centre study.

Shortened foetal femur length (FL) is a common abnormal phenotype that often causes anxiety in pregnant women, and standard clinical treatments remain unavailable. We investigated the clinical characteristics, genetic aetiology and obstetric pregnancy outcomes of foetuses with short FL and provided a reference for perinatal management of such cases. Chromosomal microarray analysis was used to analyse the copy number variations (CNV) in short FL foetuses. Of the 218 foetuses with short FL, 33 foetuses exhibited abnormal CNVs, including 19 with pathogenic CNVs and 14 with variations of uncertain clinical significance. Of the 19 foetuses with pathogenic CNVs, four had aneuploidy, 14 had deletions/duplications, and one had pathogenic uniparental diploidy. The 7q11.23 microdeletion was detected in three foetuses. The severity of short FL was not associated with the rate of pathogenic CNVs. The duration of short FL for the intrauterine ultrasound phenotype in foetuses carrying a pathogenic CNV was independent of the gestational age. Further, maternal age was not associated with the incidence of foetal pathogenic CNVs. Adverse pregnancy outcomes occurred in 77 cases, including termination of pregnancy in 63 cases, postnatal dwarfed foetuses with intellectual disability in 11 cases, and three deaths within 3 months of birth. Pathogenic CNVs closely related to foetal short FL were identified, among which the 7q11.23 microdeletion was highly associated with short FL development. This study provides a reference for the perinatal management of foetuses with short FL.