One suggested approach to improve the reproductive performance of dairy herds is through the targeted management of subgroups of biologically similar animals, such as those with similar probabilities of becoming pregnant, termed pregnancy risk. We aimed to use readily available farm data to develop predictive models of pregnancy risk in dairy cows. Data from a convenience sample of 108 dairy herds in the UK were collated and each herd was randomly allocated, at a ratio of 80:20, to either training or testing data sets. Following data cleaning, there were a total of 78 herds in the training data set and 20 herds in the testing data set. Data were further split by parity into nulliparous, primiparous, and multiparous subsets. An XGBoost model was trained to predict the insemination outcome in each parity subset, with predictors from farm records of breeding, calving and milk recording. Training data comprised 74,511 inseminations in 45,909 nulliparous animals, 86,420 inseminations in 39,439 primiparous animals, and 158,294 inseminations in 32,520 multiparous animals. The final models were evaluated by predicting with the testing data, comprising 31,740 inseminations in 19,647 nulliparous animals, 38,588 inseminations in 16,215 primiparous animals, and 65,049 inseminations in 12,439 multiparous animals. Model discrimination was assessed by calculating the area under receiver operating characteristic curves (AUC); model calibration was assessed by plotting calibration curves and compared across test herds by calculating the expected calibration error (ECE) in each test herd. The models were unable to discriminate between insemination outcomes with high accuracy, with an AUC of 0.63, 0.59 and 0.62 in the nulliparous, primiparous and multiparous subsets, respectively. The models were generally well-calibrated, meaning the model-predicted pregnancy risks were similar to the observed pregnancy risks. The mean (SD) ECE in the test herds was 0.038 (0.023), 0.028 (0.012) and 0.020 (0.008) in the nulliparous, primiparous and multiparous subsets respectively. The predictive models reported here could theoretically be used to identify subgroups of animals with similar pregnancy risk to facilitate targeted reproductive management; or provide information about cows\' relative pregnancy risk compared with the herd average, which may support on-farm decision-making. Further research is needed to evaluate the generalizability of these predictive models and understand the source of variation in ECE between herds; however, this study demonstrates that it is possible to accurately predict pregnancy risk in dairy cows using readily available farm data.

Zinpentraxin alfa is a recombinant human pentraxin-2 (PTX-2) developed for the treatment of various fibrotic diseases with the hypothesis that supplementing endogenous PTX-2 levels through intravenous administration should increase its regulatory capacity in circulation and at the site of disease, thereby promoting healing and reducing fibrosis. Zinpentraxin alfa has been studied in various clinical trials, particularly in patients with idiopathic pulmonary fibrosis, where it has demonstrated efficacy in slowing decline in lung function in a phase 2 study. In the present investigation, we summarize findings from 14-day repeat-dose toxicity studies in rats and cynomolgus monkeys supporting early clinical development of zinpentraxin alfa. In addition, we also describe the findings from the embryo-fetal developmental (EFD) studies conducted in rats and rabbits, since the intended fibrosis patient population may include patients of childbearing potential. Zinpentraxin alfa was well tolerated by rats and monkeys in general toxicity studies with no treatment-related adverse effects, as well as by pregnant rats over the same dose range in a definitive EFD study. In contrast, substantial toxicity was observed in a rabbit dose-range-finder EFD study. Zinpentraxin alfa was poorly tolerated by pregnant rabbits and effects on the dams correlated with post-implantation fetal losses. The disparate effects of zinpentraxin alfa on embryo-fetal development between the two species suggests a potential unknown biological function of PTX-2 in pregnancy in the rabbit, which may be relevant to humans. Our findings warrant the consideration for highly effective contraceptive measures to avoid pregnancy in patients enrolled in clinical studies with zinpentraxin alfa.

BACKGROUND: In this register-based study of pregnancies in Denmark, we assessed the associations between maternal age and the risk of fetal aneuploidies (trisomy 21, trisomy 18, trisomy 13, triploidy, monosomy X and other sex chromosome aberrations). Additionally, we aimed to disentangle the maternal age-related effect on fetal aneuploidies by cases with translocation trisomies and mosaicisms.
METHODS: We followed a nationwide cohort of 542 375 singleton-pregnant women attending first trimester screening in Denmark between 2008 and 2017 until delivery, miscarriage or termination of pregnancy. We used six maternal age categories and retrieved information on genetically confirmed aneuploidies of the fetus and infant from the national cytogenetic register.
RESULTS: We confirmed the known associations between advanced maternal age and higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations, especially in women aged ≥35 years, whereas we found no age-related associations with triploidy or monosomy X. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies.
CONCLUSIONS: This study provides insight into the accurate risk of fetal aneuploidies that pregnant women of advanced ages encounter.

Rheumatic heart disease (RHD) remains prevalent in the developing world and reproductive-age women are disproportionately affected. It is among the common est cardiac diseases during pregnancy and is associated with poor pregnancy outcomes. Despite its importance among reproductive-age women, there are no local studies that characterize the clinical characteristics, risk of poor pregnancy outcomes and contraception which represents one effective way to prevent unplanned pregnancies in this population.
This was a hospital-based descriptive cross-sectional study. Non-pregnant reproductive-age women with echocardiographically diagnosed RHD were consecutively recruited from in- and out-patients units of the Jakaya Kikwete Cardiac Institute (JKCI). A clinical research form was used to gather socio-demographic, clinical characteristics, contraception status and echocardiographic information. The maternal/pregnancy risk class was determined using the modified World Health Organization (WHO) classification of maternal risk.
Two hundred thirty-eight women of reproductive age with RHD were recruited. The median age (range) was 36 years (15-49). Two-thirds were dyspneic on moderate exertion and 17.2% had New York Heart Association class IV heart failure. A quarter had atrial fibrillation/flutter. On echocardiography, mitral regurgitation was the most common valvular lesion (68.1%), followed by mitral stenosis (66.8%), and 12.2% of participants had reduced left ventricular ejection fraction. Two-thirds (66%) had a high pregnancy risk (class IV) based on the modified WHO classification system. The proportion of participants using contraception was 7.1% and common methods were: bilateral tubal ligation 5 of 17 (29.4%) and hormonal implant (4 of 17). The most common reason for the choice of a method was safety, 10 out of 17 (58.8%).
The majority of women of reproductive age with RHD in our hospital cohort are at the highest pregnancy risk based on the modified WHO classification and a very small proportion of them are on contraception. These results call for action among clinicians to offer counselling to these patients, educating them on their risk and offering appropriate contraception advice while waiting for definitive interventions.

UNASSIGNED: Despite substantial progress in improving maternal and newborn health, India continues to experience high rates of newborn mortality and stillbirths. One reason may be that many births happen in health facilities that lack advanced services-such as Caesarean section, blood transfusion, or newborn intensive care. Stratification based on pregnancy risk factors is used to guide \'high-risk\' women to advanced facilities. To assess the utility of risk stratification for guiding the choice of facility, we estimated the frequency of adverse newborn outcomes among women classified as \'low risk\' in India.
UNASSIGNED: We used the 2019-21 Fifth National Family Health Survey (NFHS-5)-India\'s Demographic and Health Survey-which includes modules administered to women aged 15-49 years. In addition to pregnancy history and outcomes, the survey collected a range of risk factors, including biomarkers. We used national obstetric risk guidelines to classify women as \'high risk\' versus \'low risk\' and assessed the frequency of stillbirths, newborn deaths, and unplanned Caesarean sections for the respondent\'s last pregnancy lasting 7 or more months in the past five years. We calculated the proportion of deliveries occurring at non-hospital facilities in all the Indian states.
UNASSIGNED: Using data from nearly 176,699 recent pregnancies, we found that 46.6% of India\'s newborn deaths and 56.3% of stillbirths were among women who were \'low risk\' according to national guidelines. Women classified as \'low risk\' had a Caesarean section rate of 8.4% (95% CI 8.1-8.7%), marginally lower than the national average of 10.0% (95% CI 9.8-10.3%). In India as a whole, 32.0% (95% CI 31.5-32.5%) of deliveries occurred in facilities that were likely to lack advanced services. There was substantial variation across the country, with less than 5% non-hospital public facility deliveries in Punjab, Kerala, and Delhi compared to more than 40% in Odisha, Madhya Pradesh, and Rajasthan. Newborn mortality tended to be lower in states with highest hospital delivery rates.
UNASSIGNED: Individual risk stratification based on factors identified in pregnancy fails to accurately predict which women will have delivery complications and experience stillbirth and newborn death in India. Thus a determination of \'low risk\' should not be used to guide women to health facilities lacking key life saving services, including Caesarean section, blood transfusion, and advanced newborn resuscitation and care.
UNASSIGNED: Bill and Melinda Gates Foundation and the World Bank. The findings, interpretations and conclusions expressed in the paper are entirely those of the authors, and do not represent the views of the Gates Foundation or of the World Bank, its Executive Directors, or the countries they represent.

A lot of studies use the second-to-fourth digit length ratio (2D:4D) as a biomarker for intrauterine androgen load to predict behavioral and mental health problems. Thus, knowledge of 2D:4D\'s metric properties, namely reliability and validity, is essential.
2D:4D handscans were available from 149 adolescents (M = 13.32 years, SD = 0.35) and their mothers. For 88 adolescents, there were also primary-school age handscans (M = 7.87 years, SD = 0.68). Prenatal risks for the 1st to 3rd trimesters were recorded during the 3rd trimester of pregnancy (alcohol exposition: meconium biomarker and maternal self-report; nicotine exposition: maternal self-report; maternal depressive symptoms and subjective stress: questionnaires).
The 2D:4D ratio was highly stable from childhood to early adolescence. However, both developmental and sex effects were present: The 2D:4D ratio increased with age and was higher in adolescent girls vs. boys. Significant 2D:4D mother-child associations were found for girls. Significant main effects could be found for the prenatal risk factors alcohol (self-report) and nicotine consumption.
In line with earlier studies, the 2D:4D biomarker proved to be an inter-individually stable measure with an intra-individual increase from childhood to early adolescence. Sex differences in adolescence and associations with maternal prenatal health behaviour underline the validity of the biomarker. Findings on heritability emphasize the importance of interpreting 2D:4D results in a sex-specific manner.

This study examines alcohol consumption and smoking behaviors by pregnancy status and race/ethnicity in order to inform improved interventions designed to assist women of all races to avoid alcohol and tobacco use during pregnancy for their health and to prevent potential fetal exposure.
This retrospective secondary data analysis utilized nationally representative National Health and Nutrition Examination Survey data between 2001 and 2018. Smoking and alcohol use were evaluated by race/ethnicity and pregnancy risk. Sexual behavior, reproductive health, and prescription drug use determined pregnancy risk, categorized as low pregnancy risk, at risk of becoming pregnant, and pregnant. Binary and multinomial multivariable logistic regression were used to examine associations.
The final sample consisted of 10,019 women of which 11.8% were Mexican American, 7.7% other Hispanic, 65.5% white, and 15% black (weighted percentages). White low pregnancy risk and pregnancy risk smoked most frequently in respective pregnancy risk groups (p < 0.001). Among pregnant women, smoking prevalence was highest among black women (14.0%, p < 0.01). Pregnancy risk women were more likely to smoke and pregnant women were less likely to smoke compared with low pregnancy risk. Low pregnancy risk and pregnancy risk Hispanics had a lower prevalence of binge drinking, but prevalence decreased less among pregnant Hispanics than other racial/ethnic groups. In adjusted analyses, pregnancy risk black women had more than 2 times the odds of combined smoking and alcohol consumption compared with low pregnancy risk black women.
Women who may become pregnant need interventions and improved policy to prevent alcohol use and smoking. Culturally appropriate alcohol and smoking cessation interventions before pregnancy and improved contraception access are needed.

Limited research and guidance on the use of \"withdrawal\" or coitus interruptus for contraception lead to inconsistent or even inaccurate physician recommendations regarding its use. Consequently, patients rely on online communities to learn about this commonly used contraceptive method. To identify knowledge gaps and concerns between men and women, as well as explore how they use withdrawal, we examined withdrawal-related posts on the popular internet discussion forum, Reddit.
To explore gendered variations in withdrawal-related Reddit posts, we extracted posts from the gendered forums: \"TwoXChromosomes,\" \"Askwomen,\" \"Askmen,\" and \"OneY\" between 2010 and 2019 that contained the search terms: \"coitus interruptus,\" \"withdrawal,\" \"pull out,\" \"preejaculate,\" or \"precum.\" We developed an initial codebook with expected codes and augmented it with emerging findings from a random sampling of 10% of posts. We revised iteratively for interrater agreement, after which researchers coded the remaining posts independently.
Of 269 withdrawal-related queries, 19% were submitted by men; 81% referenced the contributor\'s own withdrawal use. Salient domains included: concerns about pregnancy risk (59%), how to effectively use withdrawal (13%), benefits/pleasure from using withdrawal (12%), impact on personal life/relationship (9%), and problems encountered, inclusive of consent (7%). Posts to female-focused forums more frequently inquired about pregnancy risk, while those on male forums more frequently inquired about withdrawal-related logistics (p < 0.001); domains were not associated with contributor gender.
Withdrawal-related queries within this Reddit sample are frequently posted by women, the majority of whom want to understand their risk of pregnancy with withdrawal. Research operationalizing withdrawal and more accurately estimating withdrawal-related pregnancy risk is warranted.
Reddit users discuss their personal experiences with withdrawal as contraception, as well as seek advice regarding its use from the online community. Pregnancy risk, logistics of use, and ongoing stigma are salient topics. Further research on pregnancy risk, operationalizing success, and approaches for discussing this behavioral method is warranted.

Two experiments were conducted with Holstein-Friesian cows in the Republic of North Macedonia and with Holstein cows in Kansas. We hypothesized that 1 dose of PGF2α administered on d 8 (Ov-8×1) instead of d 7 (Ov-7×1) in an Ovsynch program [GnRH-1 (d 0)-7 d-PGF2α-56 h-GnRH-2-16 h-timed artificial insemination (AI)] would increase the proportion of cows with complete luteolysis compared with controls receiving a single dose on d 7. Cows were treated with Ov-7×1 or with Ov-8×1 in experiment 1 (n = 347), using only a single dose of PGF2α. In experiment 2 (n = 452), a third treatment was added (Ov-7×2), in which a second dose of PGF2α was administered on d 8. Progesterone was measured in blood samples collected before the first or only PGF2α administration and 72 h later before insemination. Complete luteolysis was defined as having occurred when progesterone was ≥1 ng/mL before PGF2α and ≤0.3 ng/mL 72 h later (time of AI). Follicles and luteal structures were mapped before GnRH-1 and PGF2α administrations. The results of experiment 1 demonstrated a greater percentage of multiparous cows in OV-8×1 having complete luteal regression compared with multiparous Ov-7×1 cows, whereas treatments were equally effective in primiparous cows, as reflected in the concentrations of progesterone before AI. Furthermore, pregnancy per AI did not differ between treatments. Results in experiment 2 revealed that 99.3% of cows in the Ov-7×2 treatment receiving the second dose of PGF2α had complete luteolysis, regardless of parity, compared with significantly fewer cows in the Ov-7×1 and Ov-8×1 treatments (91.2 and 90.6%, respectively). Neither concentrations of progesterone, which averaged <0.4 ng/mL at AI, nor pregnancy per AI differed among the 3 treatments. In both experiments, when status of luteal function before PGF2α treatment was examined [cows with no corpus luteum (CL) before GnRH-1 but which had formed a new CL in response to ovulation after GnRH-1; cows with an older CL (the same CL that was detected before GnRH-1); or cows with both a new and an older CL], treatments did not differ in causing complete luteolysis. Furthermore, complete luteolysis in experiment 2 did not differ regardless of whether cows had 1, 2, or 3 or more CL before PGF2α administration. Pregnancy per AI did not differ among treatments, indicating that any of the 3 treatments might produce similar pregnancy outcomes with the flexibility of applying either of the 7- or the 8-d treatments.

OBJECTIVE: The effectiveness of physical activity (PA) programs for prevention of gestational diabetes (GDM) lacks conclusive evidence. The aim of this study was to generate clear evidence regarding the effectiveness of physical activity programs in GDM prevention to guide clinical practice.
METHODS: PubMed/Medline, ISI Web of Science, Scopus, and EMBASE were searched to identify the randomized trials (RCTs) published until June 2019. Randomised controlled trials enrolling women at high risk before the 20th week of gestation comparing the effect of PA interventions with usual care for prevention of GDM were retrieved. Data obtained were synthesised using a bias-adjusted model of meta-analysis.
RESULTS: A total of 1467 adult women in 11 eligible trials were included. The risk of GDM was significantly lower with PA, but only when it was delivered in the healthcare facility (RR 0.53; 95% CI 0.38-0.74). The number needed to treat with PA in pregnancy (compared to usual care) to prevent one GDM event was 18 (95% CI 14 - 29). The overall effect of PA interventions regardless of location of the intervention was RR 0.69 (95% CI 0.51 - 0.94).
CONCLUSIONS: This study provides evidence that in-facility physical activity programs started before the 20th week of gestation can significantly decrease the incidence of GDM among women at high risk.