Antenatal reproductive screening for pregnant people including preconception: Provides the best reproductive opportunity for informed consent, quality, and safety.

INTRODUCTION: This antenatal screening review will include reproductive screening evidence and approaches for pre-conception and post-conception, using first to third trimester screening opportunities. METHODS: Focused antenatal screening peer-reviewed publications were evaluated and summarized. RESULTS: Evidenced-based reproductive antenatal screening elements should be offered and discussed, with the pregnancy planning or pregnant person, during Preconception (genetic carrier screening for reproductive partners, personal and family (including reproductive partner) history review for increased genetic and pregnancy morbidity risks); First Trimester (fetal dating with ultrasound; fetal aneuploidy screening plus consideration for expanded fetal morbidity criteria, if appropriate; pregnant person preeclampsia screening; early fetal anatomy screening; early fetal cardiac screening); Second Trimester for standard fetal anatomy screening (18-22 weeks) including cardiac; pregnant person placental and cord pathology screening; pregnant person preterm birth screening with cervical length measurement); Third Trimester (fetal growth surveillance; continued preterm birth risk surveillance). CONCLUSION: Antenatal reproductive screening has multiple elements, is complex, is time-consuming, and requires the use of pre- and post-testing counselling for most screening elements. The use of preconception and trimesters 'one to three' requires clear patient understanding and buy-in. Informed consent and knowledge transfer is a main goal for antenatal reproductive screening approaches.

Low-dose aspirin, maternal cardiometabolic health, and offspring respiratory health 9 to 14 years after delivery: Findings from the EAGeR Follow-up Study.

BACKGROUND: Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring. OBJECTIVES: We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health. METHODS: The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma. RESULTS: Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias. CONCLUSIONS: We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.

Association between days post-conception and lactation persistency in dairy cattle.

Determining the optimal insemination moment for individual cows is complex, particularly when considering the effects of pregnancy on milk production. The effect of pregnancy on the absolute milk yield has already been reported in several studies. Currently, there is limited quantitative knowledge about the association between days post-conception (DPC) and lactation persistency, based on a lactation curve model, and, specifically, how persistency changes during pregnancy and relates to the days in milk at conception (DIMc). Understanding this association might provide valuable insights to determine the optimal insemination moment. This study, therefore, aimed to investigate the association between DPC and lactation persistency, with an additional focus on the influence of DIMc. Available milk production data from 2005 to 2022 were available for 23,908 cows from 87 herds located throughout the Netherlands and Belgium. Persistency was measured by a lactation curve characteristic decay, representing the time taken to halve milk production after peak yield. Decay was calculated for 8 DPC (0, 30, 60, 90, 120, 150, 180, and 210 d after DIMc) and served as the dependent variable. Independent variables included DPC, DIMc (≤60, 61-90, 91-120, 121-150, 151-180, 181-210, >210), parity group, DPC × parity group, DPC × DIMc, and variables from 30 d before DIMc as covariates. The results showed an increase in decay, which is to say, a decrease in persistency, during pregnancy for both parity groups, albeit in different ways. Specifically, from DPC 150 to DPC 210, multiparous cows showed a greater decline in persistency compared with primiparous cows. Furthermore, a later DIMc (cows conceiving later) was associated with higher persistency. Except for the early DIMc groups (DIMc <90), DIMc does not affect the change in persistency by gestation. The findings from this study contribute to a better understanding of how DPC and DIMc during lactation influence lactation persistency, enabling more informed decision-making by farmers who wish to take persistency into account in their reproduction management.

Quantifying the Impacts of Pre- and Post-Conception TSH Levels on Birth Outcomes: An Examination of Different Machine Learning Models.

Background: While previous studies identified risk factors for diverse pregnancy outcomes, traditional statistical methods had limited ability to quantify their impacts on birth outcomes precisely. We aimed to use a novel approach that applied different machine learning models to not only predict birth outcomes but systematically quantify the impacts of pre- and post-conception serum thyroid-stimulating hormone (TSH) levels and other predictive characteristics on birth outcomes. Methods: We used data from women who gave birth in Shanghai First Maternal and Infant Hospital from 2014 to 2015. We included 14,110 women with the measurement of preconception TSH in the first analysis and 3,428 out of 14,110 women with both pre- and post-conception TSH measurement in the second analysis. Synthetic Minority Over-sampling Technique (SMOTE) was applied to adjust the imbalance of outcomes. We randomly split (7:3) the data into a training set and a test set in both analyses. We compared Area Under Curve (AUC) for dichotomous outcomes and macro F1 score for categorical outcomes among four machine learning models, including logistic model, random forest model, XGBoost model, and multilayer neural network models to assess model performance. The model with the highest AUC or macro F1 score was used to quantify the importance of predictive features for adverse birth outcomes with the loss function algorithm. Results: The XGBoost model provided prominent advantages in terms of improved performance and prediction of polytomous variables. Predictive models with abnormal preconception TSH or not-well-controlled TSH, a novel indicator with pre- and post-conception TSH levels combined, provided the similar robust prediction for birth outcomes. The highest AUC of 98.7% happened in XGBoost model for predicting low Apgar score with not-well-controlled TSH adjusted. By loss function algorithm, we found that not-well-controlled TSH ranked 4th, 6th, and 7th among 14 features, respectively, in predicting birthweight, induction, and preterm birth, and 3rd among 19 features in predicting low Apgar score. Conclusions: Our four machine learning models offered valid predictions of birth outcomes in women during pre- and post-conception. The predictive features panel suggested the combined TSH indicator (not-well-controlled TSH) could be a potentially competitive biomarker to predict adverse birth outcomes.

Early post-conception maternal cortisol, children's HPAA activity and DNA methylation profiles.

The hypothalamic-pituitary-adrenal axis (HPAA) plays a critical role in the functioning of all other biological systems. Thus, studying how the environment may influence its ontogeny is paramount to understanding developmental origins of health and disease. The early post-conceptional (EPC) period could be particularly important for the HPAA as the effects of exposures on organisms' first cells can be transmitted through all cell lineages. We evaluate putative relationships between EPC maternal cortisol levels, a marker of physiologic stress, and their children's pre-pubertal HPAA activity (n=22 dyads). Maternal first-morning urinary (FMU) cortisol, collected every-other-day during the first 8 weeks post-conception, was associated with children's FMU cortisol collected daily around the start of the school year, a non-experimental challenge, as well as salivary cortisol responses to an experimental challenge (all Ps5% change in children's buccal epithelial cells' DNA methylation for 867 sites, while children's HPAA activity was associated with five CpG sites. Yet, no CpG sites were related to both, EPC cortisol and children's HPAA activity. Thus, these epigenetic modifications did not statistically mediate the observed physiological links. Larger, prospective peri-conceptional cohort studies including frequent bio-specimen collection from mothers and children will be required to replicate our analyses and, if our results are confirmed, identify biological mechanisms mediating the statistical links observed between maternal EPC cortisol and children's HPAA activity.

The window period of NEUROGENIN3 during human gestation.

The basic helix-loop-helix transcription factor, NEUROG3, is critical in causing endocrine commitment from a progenitor cell population in the developing pancreas. In human, NEUROG3 has been detected from 8 weeks post-conception (wpc). However, the profile of its production and when it ceases to be detected is unknown. In this study we have defined the profile of NEUROG3 detection in the developing pancreas to give insight into when NEUROG3-dependent endocrine commitment is possible in the human fetus. Immunohistochemistry allowed counting of cells with positively stained nuclei from 7 wpc through to term. mRNA was also isolated from sections of human fetal pancreas and NEUROG3 transcription analyzed by quantitative reverse transcription and polymerase chain reaction. NEUROG3 was detected as expected at 8 wpc. The number of NEUROG3-positive cells increased to peak levels between 10 wpc and 14 wpc. It declined at and after 18 wpc such that it was not detected in human fetal pancreas at 35-41 wpc. Analysis of NEUROG3 transcription corroborated this profile by demonstrating very low levels of transcript at 35-41 wpc, more than 10-fold lower than levels at 12-16 wpc. These data define the appearance, peak and subsequent disappearance of the critical transcription factor, NEUROG3, in human fetal pancreas for the first time. By inference, the window for pancreatic endocrine differentiation via NEUROG3 action opens at 8 wpc and closes between 21 and 35 wpc.

Spontaneous intra-uterine growth restriction modulates the endocrine status and the developmental expression of genes in porcine fetal and neonatal adipose tissue.

Low birth weight is correlated with low adiposity at birth, a phenotype that influences neonatal survival and later adiposity. A better understanding of events affecting the fetal adipose tissue development and its functionality around birth is thus needed. This study was undertaken to examine the impact of spontaneous intra-uterine growth restriction (IUGR) on circulating concentrations of hormones and nutrients together with the developmental expression patterns of various genes in subcutaneous adipose tissue of pig fetus during the last third of pregnancy and just after birth. At 71 and 112 days post-conception and 2 days postnatal, pairs of same-sex piglets were chosen within litters to have either a medium (MBW) or a low (LBW) weight (n=6 pairs at each stage). The results indicate that IUGR counteracts the temporal fall of DLK1 gene expression in developing adipose tissue across gestation. It also attenuates the time-dependent increase in expression levels of many genes promoting adipocyte differentiation (PPARG, CEBPA) and lipogenesis (LPL, SREBF1, FASN, FABP4). Opposite responses to IUGR were observed for the IGF system, so that IGF1 mRNA levels were lower (P<0.001) but IGF2 mRNA levels were greater in adipose tissue of LBW piglets compared with MBW piglets. The plasma insulin concentration and the mRNA levels of insulin receptor (INSR) and insulin-responsive glucose transporter (GLUT4) in adipose tissue were also greater in LBW piglets at day 2 postnatal. The data indicate that IUGR delays the normal ontogeny of adipose tissue across gestation and affects the insulin and IGF axes around birth.

Core promoter analysis of porcine Six1 gene and its regulation of the promoter activity by CpG methylation.

Six1, an evolutionary conserved transcription factor, has been shown to play an important role in organogenesis and diseases. However, no reports were shown to investigate its transcriptional regulatory mechanisms. In the present study, we first identified porcine Six1 gene core promoter region (+170/-360) using luciferase reporter assay system and found that promoter activities were significantly higher in the mouse myoblast C2C12 cells than that in the mouse fibroblast C3H10T1/2 cells, implying that Six1 promoter could possess muscle-specific characteristics. Moreover, our results showed that promoter activities of Six1 were decreased as induction of differentiation of C2C12 cells, which was accompanied by the down-regulation of mRNA expression of Six1 gene. In addition, we found that the DNA methylation of Six1 promoters in vitro obviously influences the promoter activities and the DNA methylation level of Six1 promoter core region was negatively correlated to Six1 gene expression in vivo. Taken together, we preliminarily clarified transcriptional regulatory mechanisms of Six1 gene, which should be useful for investigating its subtle transcriptional regulatory mechanisms in the future. On the other hand, based on Six1 involved in tumorigenesis, our data also provide a genetic foundation to control the generation of diseases via pursuing Six1 as therapeutic target gene.

Development of the penis during the human fetal period (13 to 36 weeks after conception).

PURPOSE: We analyzed the development of the area of the penis and erectile structures (corpora cavernosa and corpus spongiosum) and the thickness of the tunica albuginea during the fetal period (13 to 36 weeks after conception) in humans to establish normative patterns of growth. MATERIALS AND METHODS: We studied 56 male human fetuses at 13 to 36 weeks after conception. We used histochemical and morphometric techniques to analyze the parameters of total penile area, area of corpora cavernosa, area of corpus spongiosum, and thickness of tunica albuginea in the dorsal and ventral regions using ImageJ software (National Institutes of Health, Bethesda, Maryland). RESULTS: Between 13 and 36 weeks after conception the area of the penis varies from 0.95 to 24.25 mm2. The area of the corpora cavernosa varies from 0.28 to 9.12 mm2, and the area of the corpus spongiosum varies from 0.14 to 3.99 mm2. The thickness of the tunica albuginea varies from 0.029 to 0.296 mm in the dorsal region and from 0.014 to 0.113 mm in the ventral region of the corpora cavernosa. CONCLUSIONS: We found a strong correlation between the total penile area, corpora cavernosa and corpus spongiosum with fetal age (weeks following conception). The growth rate was more intense during the second trimester (13 to 24 weeks of gestation) compared to the third trimester (25 to 36 weeks). Tunica albuginea thickness also was strongly correlated with fetal age and this structure was thicker in the dorsal vs ventral region.