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BACKGROUND: The emergence of cellfree fetal DNA (cfDNA) testing technology has disrupted the landscape of prenatal screening for trisomies 21 (T21) and 18 (T18). Publicly funded systems around the world are grappling with how to best integrate this more accurate but costly technology, as there is limited evidence about its incremental value in real-world conditions. The objectives of this study were to describe the population-based performance of Ontario's prenatal screening program, which incorporates publicly funded cfDNA screening for specific indications, and the effect of cfDNA testing on the screening and diagnostic choices made by pregnant people. METHODS: We conducted a retrospective, descriptive cohort study using routinely collected data from Better Outcomes & Registry Network (BORN) Ontario, which captures linked population data for prenatal and neonatal health encounters across Ontario. We included all singleton pregnancies with an estimated due date between Sept. 1, 2016, and Mar. 31, 2019, that underwent publicly funded prenatal screening in Ontario, and a comparison cohort from Apr. 1, 2012, and Mar. 31, 2013. We assessed performance of the screening program for the detection of T21 or T18 by calculating sensitivity, specificity, positive predictive value and negative predictive value against diagnostic cytogenetic results or birth outcomes. We assessed the impact of the program by calculating the proportion of T21 screen-positive pregnancies undergoing subsequent cfDNA screening and invasive prenatal diagnostic testing. RESULTS: The study cohort included 373682 pregnancies. The prenatal screening program had an uptake of 69.9%, a screen-positive rate and sensitivity of 1.6% and 89.9% for T21, and 0.2% and 80.5% for T18, respectively. The test failure rate for cfDNA screening was 2.2%. Invasive prenatal diagnostic testing decreased from 4.4% in 2012-2013 to 2.4% over the study period; 65.2% of pregnant people who received a screen-positive result from cfDNA testing went on to have invasive prenatal diagnostic testing. INTERPRETATION: This publicly funded screening program, incorporating cfDNA analysis for common aneuploidies, showed robust performance, a substantial reduction in invasive prenatal diagnostic testing and that pregnant people exercise autonomy in their choices about prenatal screening and diagnosis., Offering screening for chromosomal aneuploidies, including trisomies 21 (T21) and 18 (T18), is part of routine prenatal care. To this end, multiple marker screening, which uses a combination of ultrasound [...]

(Abstracted from Am J Obstet Gynecol2023;229:168.e1–e8)Cell-free DNA (cfDNA) screening is a form of prenatal genetic screening for aneuploidies. This method boasts lower false-positive rates than multiple-marker screening methods and is now commonly recommended.

Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions.

CeO2/g-C3N4photocatalysts have attracted tremendous attention in the photocatalytic degradation of organic pollutants. The design and construction of highly active CeO2/g-C3N4photocatalysts without harsh conditions are still challenging. Herein, highly dispersed CeO2–xnanoparticles with rich oxygen vacancies were successfully precipitated on the surface of g-C3N4under mild conditions. The fabricated CeO2–x/g-C3N4exhibits remarkable activity and stability for photocatalytic degradation of MO pollutant. The optimal rate constant of MO degradation over CeO2–x/g-C3N4is about 0.031 min−1, which is three times higher than that of g-C3N4. A negligible activity decrease is observed after three cycling runs. The enhanced catalytic performance can be ascribed to the excellent dispersion of CeO2–xwith rich oxygen vacancies that benefit O2adsorption and visible light absorption. In addition, the proper band alignment between CeO2–xand g-C3N4is conducive to the highly efficient separation of photogenerated electron–hole pairs.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2004.12.017 Byline: Tianhua Huang (a), Titus Owolabi (b), Anne M. Summers (a), Chris Meier (a), Philip R. Wyatt (a) Abstract: The purpose of this study was to investigate associations between risk of spontaneous fetal loss and risk estimates for Down syndrome, trisomy 18, and neural tube defects assigned by second-trimester maternal serum screening. Author Affiliation: (a) Ontario Maternal Serum Screening Database and Genetics Program (b) Maternal Newborn Program, North York General Hospital, Toronto, Ontario, Canada Article History: Received 18 March 2004; Revised 11 November 2004; Accepted 7 December 2004

Pregnant women who have excessive amounts of human chorionic gonadotropin in their blood are more likely to have an adverse pregnancy outcome such as miscarriage, low birth weight babies, premature birth, fetal growth restriction, and hypertension. This was the conclusion of a study of 3,870 pregnant women. Pregnant women with high blood levels of human chorionic gonadotropin should receive extensive prenatal care.

Pregnant women who test positive for both Down syndrome and neural tube defects have a high risk of carrying a baby with birth defects and chromosomal abnormalities, according to a study of 170,394 women. The 189 women who had a double-positive test were also more likely to experience preeclampsia, fetal growth retardation, premature birth, miscarriage, and fetal death.

To explore the role of maternal ethnicity as a risk factor for obstetrical anal sphincter injury (OASI).

Objectives: To examine the racial differences in the population attributable fraction (PAF) of prepregnancy obesity and excessive gestational weight gain to large-for-gestational-age (LGA) neonates. Methods: We conducted a population-based retrospective cohort study among all women who had prenatal screening and had a singleton live birth in a hospital (1 April 2016–31 March 2017) using data from Ontario birth registry in Canada. We used multivariable log-binomial regression models to estimate the PAF and 95% confidence interval (CI) of LGA neonates due to prepregnancy obesity and excessive gestational weight gain. All models were stratified by race (White, Asian, and Black). Results: Of the 74,402 eligible women, the prevalence of prepregnancy obesity, excessive gestational weight gain, and LGA neonate was 21.1%, 60.0%, and 11.3%, respectively, for Whites; 9.3%, 45.9%, and 5.4%, respectively, for Asians; and 28.6%, 52.4%, and 7.9%, respectively, for Blacks. The association of prepregnancy obesity was greater than that of excessive gestational weight gain on LGA for all racial groups. Excessive gestational weight gain contributed more than prepregnancy obesity in Whites (PAF 32.9%, 95% CI [30.3–35.5%] and 16.6%, 95% CI [15.3–17.9%], respectively, for excessive gestational weight gain and prepregnancy obesity) and in Asians (PAF 32.1%, 95% CI [27.2–36.7%] and 11.8%, 95% CI [9.5–14.1%], respectively, for excessive gestational weight gain and prepregnancy obesity). Prepregnancy obesity (PAF 22.8%, 95% CI [17.1–28.1%]) and excessive gestational weight gain (PAF 20.1%, 95% CI [4.7–33.0%]) contributed to LGA neonates almost the same in Blacks. Conclusions: Excessive gestational weight gain contributed more to LGA neonates than prepregnancy obesity in Whites and Asians, while there was no difference between excessive gestational weight gain and prepregnancy obesity in their contributions to the LGA neonates in Blacks. The differences are mostly driven by the differential prevalence of the two risk factors across racial groups.

Objective: To explore inadequate and excessive gestational weight gain (GWG) among pregnant women of different racial/ethnic backgrounds in Ontario, Canada. Methods: A population-based retrospective cohort study was conducted among women who had prenatal screening and had a singleton birth in an Ontario hospital between April 2016 and March 2017. We estimated adjusted risk ratios (aRR) of racial/ethnic differences for inadequate or excessive GWG using multinomial logistic regression models. Interaction effects were examined to determine whether racial/ethnic difference in GWG varied by pre-pregnancy body mass index (BMI). Results: Among 74,424 women, the prevalence of inadequate GWG in White, Asian, and Black women was 15.7%, 25.8%, and 25.0%, and excessive GWG was 62.8%, 45.5%, and 54.7%, respectively. There were significant interaction effects between race/ethnicity and pre-pregnancy BMI for inadequate GWG (Wald p?<?0.01) and excessive GWG (Wald p?<?0.01). Compared with White women, Asian women had higher risk of inadequate GWG and lower risk of excessive GWG in all weight classes, and Black women had higher risk of inadequate GWG and lower risk of excessive GWG if their BMI was normal, overweight, or obese. Conclusion: Variations in unhealthy GWG by pre-pregnancy weight classes among Ontario White, Asian and Black women were observed. Individualized counseling regarding appropriate GWG is universally recommended. Additional consideration of racial/ethnic variations by maternal weight classes may help to promote healthy GWG in Canada.

Some maternal hormone levels in pregnancy are associated with a higher risk of breast and ovarian cancer. This study systematically assessed the association between blood hormone levels measured in pregnancy and future risk of these cancers.

The objectives of this study were as follows: (1) to investigate the accuracy of IVF identification on the prenatal screening record from prenatal screening laboratories; (2) to compare the screening markers in IVF and non-IVF pregnancies in the population of Ontario; and (3) to propose more appropriate IVF adjustment factors for the Ontario population.

To assess the performance of first trimester combined screening (FTS) when enhanced with placental growth factor and alpha feto-protein in the detection of trisomies 18 and 13.

Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system.

(Abstracted from BMJ2018;362:k2739)Placental vascular disease is thought to arise within the temporary interface of the trophoblast and endometrial decidua, resulting in adverse outcomes for mother and fetus, including preeclampsia, placental abruption, poor fetal growth, and preterm birth. Some risk factors for placental vascular disease, including for preeclampsia, are the same as those for cardiovascular disease.

Microenvironment signals play a critical role in directing the differentiation of stem cells. Sertoli cells (SCs) provide a unique microenvironment that is essential for germ cell differentiation. Our previous study has demonstrated that human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (HUMSCs) could differentiate towards male germ cells in vitro, but HUMSC-derived germ-like cells expressed only few germ cell markers. The aim of this study was to investigate the effect of SCs on the differentiation of HUMSCs towards male germ cells using a co-culture system that mimicked the in vivomale germ cell microenvironment. HUMSCs formed clump-like features on SC monolayers after seeding for 3 weeks. Differentiated cells formed round colonies that share the morphological features of spermatogonial colonies. RT-PCR, immunofluorescence, confocal microscopy, and Western blot analyses revealed the expression of early germ cell markers STELLA and VASA and male germ cell-specific marker DAZL in differentiated HUMSCs, confirming the presence of cells with characteristics of male germ cells. The HUMSC-SC co-culture system mimics a native microenvironment for germ cell colonization without any in vitroartificial manipulation and can be used to explore the mechanisms controlling the differentiation of male germ cells from HUMSCs. Male germ cells derived from HUMSCs may be used in the therapy for male infertility.

Abstract: Apoptosis may be closely involved in diabetes-induced embryonic malformations. We aimed to investigate the occurrence of apoptosis at an early stage of development, in oocytes and 2-cell embryos of streptozotocin-induced diabetic mice and nondiabetic mice. Diabetic mouse ovarian sections stained with hematoxylin and eosin showed reduced number of growing follicles and delayed oocyte development. Annexin V-positive oocytes were higher in number in diabetic mice than in nondiabetic mice. Quantitative RT-PCR and immunofluorescence analysis revealed the expression of Bax and caspase-3 significantly higher in diabetic than nondiabetic oocytes. In contrast, 2-cell embryos of diabetic and nondiabetic mice showed no annexin V-positive staining. Bax expression was elevated in diabetic 2-cell embryos, but caspase-3 expression did not significantly differ between diabetic and nondiabetic 2-cell embryos. Electron microscopy revealed increased number of swollen mitochondria in diabetic 2-cell embryos. These results suggested that maternal diabetes might increase oocyte apoptosis by a Bax-caspase-3 pathway to play a role in embryonic malformations by delayed oocyte development. Development of 2-cell embryos might be adversely affected by maternal diabetes, but not through Bax-regulated caspase-3 apoptotic pathway.

The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada.

To assess the utility of uterine artery Doppler study and the risk of fetal growth restriction (FGR) in the presence of abnormal serum analytes in the first trimester screening (FTS).

The study evaluates the differences between Aboriginal and Caucasian women in the levels of maternal serum markers used in second-trimester Down syndrome screening (alpha-fetoprotein, unconjugated estriol, and total human chorionic gonadotrophin). A case-control study compared the levels of serum markers in 401 Aboriginal women and 1565 matched controls selected from 7717 Caucasian women. The cases and controls were screened in a single centre and matched for maternal age, parity, and sample date. Women with multiple pregnancies and pregnancies associated with Down syndrome, open neural tube defects, trisomy 18, and insulin-dependent diabetes mellitus as well as women without weight recorded were excluded from the study. No differences in the levels of maternal serum alpha-fetoprotein and total human chorionic gonadotrophin were observed between the two groups. Maternal serum unconjugated estriol was 12% higher in Aboriginal women. Since Aboriginal women make up only a small proportion of women screened, correcting the level of uE3 for this group will have little effect on the overall screening performance. However, if these results are confirmed by further study, individual centres may consider making this correction, so optimal screening performance can be achieved in Aboriginal women. Copyright © 2003 John Wiley & Sons, Ltd.

ObjectiveTo examine whether abnormal prenatal biochemical screening results are associated with an increased risk of premature cardiovascular disease after pregnancy.DesignPopulation based cohort study.SettingThe entire province of Ontario, Canada, where healthcare is universally available.ParticipantsWomen aged 12-55 years, without pre-existing cardiovascular disease, who underwent prenatal screening between 1993 and 2011. One pregnancy per woman was randomly selected.ExposuresLow (≤5th centile multiple of the median) serum total chorionic gonadotropin, unconjugated estriol, and pregnancy associated plasma protein A and high (≥95th centile multiple of the median) alphafetoprotein and dimeric inhibin-A.Main outcome measuresComposite of hospital admission or revascularisation for coronary artery, cerebrovascular, or peripheral arterial disease or hospital admission for heart failure or dysrhythmia at least 365 days after pregnancy.ResultsAmong 855 536 pregnancies, and after a median of 11.4 (interquartile range 6.8-17.5) years of follow-up, 6209 women developed the main cardiovascular disease outcome. Abnormal results for each of the five prenatal biochemical screening analytes, especially dimeric inhibin-A, were associated with a higher risk of cardiovascular disease. Women with an abnormally high dimeric inhibin-A (≥95th centile) had the highest rate of cardiovascular disease (30 events or 8.3 per 10 000 person years versus 251 events or 3.8 per 10 000 person years for those <95th centile; multivariable adjusted hazard ratio 2.0, 95% confidence interval 1.4 to 3.0). Compared with women without any abnormal biochemical measure, the hazard ratio for the cardiovascular disease composite outcome was 1.2-1.3 times higher with one abnormal analyte and 1.5-2.0 times higher with two or more abnormal analytes.ConclusionsWomen with abnormal prenatal biochemical screening results, especially for dimeric inhibin-A, may be at higher risk of cardiovascular disease. If these findings are replicated elsewhere, a massive amount of data exists that could aid in identifying women at higher risk of premature cardiovascular disease and that could be conveyed to them or their healthcare providers.

Infertility affects 15% of couples, about 50% infertility caused by male and growing evidence suggested an increasing problems in male reproductive. Recent studies have demostrated that adult stem cells have more flexible potentials than expected, and possessed the plasticity and capacity to transdifferentiate into mutilineage cells, including germ cells. Human umbilical cord-derived mesenchymal stem cells (HUCMSCs) possess stem cell properties. In this study, we cultured HUCMSCs, and assessed the possibility of HUCMSCs differentiated into human male germ cells in vivo and in vitro, and find a new source of cells for the transplantation to the male infertility.The ethics committee of our institution approved this study. HUCMSCs were isolated from the Wharton's jelly of the umbilical cord, clonally expanded. To investigate the capacity of differentiation in vitro, HUCMSCs were treated with human menopausal gonadotropinn (HMG) and retinoid acid (RA) in vitro. While investigate the capacity of differentiation in vivo, HUCMSCs were transplanted into the seminiferous tubules of busulfan-treated mice testes after labeled with pIRES2-EGFP or bromodeoxyuridine (BrdU). After induction in vitro, the morphologic changes of the differentiated cells were detected by phase contrast microscopy?Aelectron microscopy and transmission electron microscope?Gthe male germ cell markers were detected by immunohistochemistry, Western-blot and PT-PCR. HUCMSCs were also transplanted into the seminiferous tubules of the busulfan-treated mice by microinjection. To assess the fate of HUCMSCs in the testis, the survival?Amigration and germ cell markers of the HUCMSCs in the infertility mice testis were detected by immunohistochemistry?A immunofluorescence.HUCMSCs can express some some molecular markers of germ cells after induction. Immunohistochemistry revealed that HUCMSCs can survive in the mice testis at least 120 days, and they can migrate from the lumens to the basement membrane then to lumens again. Immunofluorescence showed that HUCMSCs can go further differentiation in the mice favorable testicular environment, and express the germ cell markers.These suggested that HUCMSCs may differentiate into male germ cell-like cells after induced by HMG and RA in vitro; and it could survive also in a favorable testicular environment, may differentiate into germ cell lineages. This finding may provide a new strategy for the treatment of male infertility.No relevant conflicts of interest to declare.

Islet transplantation is an effective way of reversing type 1 diabetes. However, islet transplantation has been hampered by problems, such as immune rejection, and the scarcity of donor islets. Human Umbilical Cord Wharton's Jelly-derived Mesenchymal Stem Cells (huMSCs), which can be differentiated into insulin-producing cells could provide a source of cells for transplant.Vitro Research We isolated and cultured huMSCs, and induced huMSCs differentiated into insulin-producing cells in the condition of islet cells grows. The morphology of huMSCs after induction were monitored by under inversion phase contrast microscope?GImmunocytochemical methods were used to detect the insulin and glucagon protein, and reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect Human insulin gene and PDX-1 gene. Dithizon-stained was used to detect zinc hydronium and radio-immunity was used to detect insulin level of culture supernatant.Vivo Research huMSCs were transplanted into the body of diabetic rats through vena caudalis, and then we observed the change of blood glucose?Abody weight ?Aserum insulin levels and survival ratio in STZ-induced diabetic rats. We detected human insulin by immunohistochemistry and RT-PCR. HE stain was used to detect the morphological changes of rat's pancreatic island.Vitro Research The morphology of huMSCs under medicine induction gradually changed from fibroblast to round and some of then had the tend of forming clusters.?GThe result of immunocytochemical showed that the expression of human insulin and glucagon was positive after treatment with medicine?GhuMSCs induced by medicine can express insulin and PDX-1 gene by RT-PCR?GDithizon stain show that the cytoplasm of huMSCs after induction were stained in Brownish red color?Gthe results of radio-immunity manifested that the insulin quantity secreted by medicine induction were significant differences compared with control group(t??6.183,P<0.05). Vivo Research When transplanted into Streptozotocin(STZ)-treated diabetics rats, huMSCs can decreased blood glucose, increased body weight and survival ratio in diabetic rats?GAfter being transplanted for one month, we discovered that it can be planted into rat's pancreas and liver by Hoechst33258?Gimmunohistochemistry and RT-PCR show that the pancreas of rat can express human insulin?Gthe morphology of rats' pancreatic island was repaired obviously if compared with diabetic rats before the transplantation through HE-stain.huMSCs can be differentiated into insulin-producing cells in vitro or in vivo. Therefore, huMSCs have the potential to become an excellent candidate in β cell replacement therapy of diabetes.No relevant conflicts of interest to declare.

Abstract 4581

Salvia miltiorrhiza is a traditional Chinese herb with thousands of years history. Composite salvia injection (CSI), a widely used administration in China nowadays, consists of Salvia miltiorrhiza, notoginseng, radix and borneo. It can promote blood flow, but also regulate qi to alleviate pain. So it is frequently used for angina, coronary heart disease and chest discomfort. Recently, some laboratory studies show that CSI may have the effect of cell induction.. In this study, we aim to investigate its neural induction. Objective: To investigate the differentiation-inducing effects of salvia miltiorrhiza on umbilical cord blood mesenchymal stem cells. Methods: The immunophenotypes of human umbilical cord blood-derived mesenchymal stem cells(MSCs) were determined by flow-cytometry. Salvia miltiorrhiza was adapted to induce the differentiation of the primary cultured cells of umbilical cord blood and MSCs. The results were compared with nerve growth factor(NGF) and ganglioside(GM1). The differentiated and undifferentiated cells were identified with immunocytochemistry. Results: In primary culture, certain cells proliferated and formed cell clusters. These cells were either fibroblast-like or round in shape with various sizes. The positive rates for MSCs phenotypes CD29, CD44, CD59 of primary culture cells were 10.7%,37.27% and 66.67%, respectively. Salvia miltiorrhiza could induce the primary cultured cells of umbilical cord blood to express neural phenotypes. After passage, the MSCs could be maintained in vitro for extended periods with stable population doubling. The positive rates for CD29, CD44, CD59 of human umbilical cord blood-derived MSCs were 40.2%,70.5% and 95.4%, respectively. Salvia miltiorrhiza could induce the MSCs to express three kinds of proteins: nestin(the marker of neuronal precursor stem cells), β-TubulinIII and neurofilament (NF) (the marker of neuronal phenotypes) and glial fibrillary acidic protein(GFAP, the marker of astrocyte). Besides, NGF and GM1 could also induce the same MSCs to nerve-like cell, which could express the same markers: β-TubulinIII, NF and GFAP. In comparison NGF and GM1, the induction effect of salvia miltiorrhiza demonstrated the higher rate of expressing neuron phenotypes at a faster speed. Conclusion: The human MSCs could be isolated from human umbilical cord blood. Salvia miltiorrhiza can induce the MSCs to differentiate into nerve-like cells, therefore, might act as a potential drug for neural induction.