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BACKGROUND: The diagnosis of failure to progress, the most common indication for intrapartum cesarean delivery, is based on the assessment of cervical dilation and station over time. Labor curves serve as references for expected changes in dilation and fetal descent. The labor curves of Friedman, Zhang et al, and others are based on time alone and derived from mothers with spontaneous labor onset. However, labor induction is now common, and clinicians also consider other factors when assessing labor progress. Labor curves that consider the use of labor induction and other factors that influence labor progress have the potential to be more accurate and closer to clinical decision-making. OBJECTIVE: This study aimed to compare the prediction errors of labor curves based on a single factor (time) or multiple clinically relevant factors using two modeling methods: mixed-effects regression, a standard statistical method, and Gaussian processes, a machine learning method. STUDY DESIGN: This was a longitudinal cohort study of changes in dilation and station based on data from 8022 births in nulliparous women with a live, singleton, vertex-presenting fetus ≥35 weeks of gestation with a vaginal delivery. New labor curves of dilation and station were generated with 10-fold cross-validation. External validation was performed using a geographically independent group. Model variables included time from the first examination in the 20 hours before delivery; dilation, effacement, and station recorded at the previous examination; cumulative contraction counts; and use of epidural anesthesia and labor induction. To assess model accuracy, differences between each models predicted value and its corresponding observed value were calculated. These prediction errors were summarized using mean absolute error and root mean squared error statistics. RESULTS: Dilation curves based on multiple parameters were more accurate than those derived from time alone. The mean absolute error of the multifactor methods was better (lower) than those of the single-factor methods (0.826 cm [95% confidence interval, 0.820-0.832] for the multifactor machine learning and 0.893 cm [95% confidence interval, 0.885-0.901] for the multifactor mixed-effects method and 2.122 cm [95% confidence interval, 2.108-2.136] for the single-factor methods; P

OBJECTIVE:  The aim of Placental Assessment in Response to Environmental Pollution Study (PARENTs) was to determine whether imaging of the placenta by novel multiparametric magnetic resonance imaging (MRI) techniques in early pregnancy could help predict adverse pregnancy outcomes (APOs) due to ischemic placental disease (IPD). Additionally, we sought to determine maternal characteristics and environmental risk factors that contribute to IPD and secondary APOs. STUDY DESIGN:  Potential patients in their first trimester of pregnancy, who agreed to MRI of the placenta and measures of assessment of environmental pollution, were recruited into PARENTs, a prospective population-based cohort study. Participants were seen at three study visits during pregnancy and again at their delivery from 2015 to 2019. We collected data from interviews, chart abstractions, and imaging. Maternal biospecimens (serum, plasma, and urine) at antepartum study visits and delivery specimens (placenta, cord, and maternal blood) were collected, processed, and stored. The primary outcome was a composite of IPD, which included any of the following: placental abruption, hypertensive disease of pregnancy, fetal growth restriction, or a newborn of small for gestational age. RESULTS:  In this pilot cohort, of the 190 patients who completed pregnancy to viable delivery, 50 (26%) developed IPD. Among demographic characteristics, having a history of prior IPD in multiparous women was associated with the development of IPD. In the multiple novel perfusion measurements taken of the in vivo placenta using MRI, decreased high placental blood flow (mL/100 g/min) in early pregnancy (between 14 and 16 weeks) was found to be significantly associated with the later development of IPD. CONCLUSION:  Successful recruitment of the PARENTs prospective cohort demonstrated the feasibility and acceptability of the use of MRI in human pregnancy to study the placenta in vivo and at the same time collect environmental exposure data. Analysis is ongoing and we hope these methods will assist researchers in the design of prospective imaging studies of pregnancy. KEY POINTS: · MRI was acceptable and feasible for the study of the human placenta in vivo.. · Functional imaging of the placenta by MRI showed a significant decrease in high placental blood flow.. · Measures of environmental exposures are further being analyzed to predict IPD..

Background: Many health education institutions in African countries such as Nigeria face increasing enrolment of students but lack an adequate number of instructors to train them. If digital learning can be demonstrated effective in augmenting knowledge and skills, this approach could help fill this gap and improve education efficiency. A needs assessment in two Nigerian midwifery schools confirmed that digital learning would be feasible and welcomed. In this study, the Midwifery Active Digitization Empowerment Initiative (MADE-I) program was tested to determine if digital delivery of the Fundamental Interventions, Referral and Safe Transfer (FIRST) course is at least equally effective for training midwifery students compared to conventional small-group delivery. Methods: A non-inferiority randomized controlled trial design was used, enrolling 130 s-year students from 2 midwifery schools in Benue State, Nigeria. Students were randomly assigned into six cohorts. Each cohort received half of the course on a Learning Management Platform on their mobile phones, the other half through standard small-group teaching. Students' knowledge, thinking, and technical skills were assessed using a pre-test, post-test, Objective Structured Clinical Exam (OSCE), and daily modular quizzes. The data was analyzed using the difference-in-difference method. Results: The study revealed that post-intervention student knowledge and thinking skills did not significantly differ between digital learning (75.26%) and small-group learning arms of the trial (75.02%, p = 0.404). Student knowledge improved significantly compared to the pre-test in both groups (by 25.03 points in the digital arm, 26.39, in small-group). Some differences were observed between digital and small-group learning in disaggregated analysis by specific module and midwifery school. Although there was a trend toward small-group learning of technical skills being more effective than digital learning, no significant differences between groups were observed in the post-intervention OSCE. Students in both groups learned equally well regardless of age, gender, and midwifery school entrance exam score. Conclusion: Digital learning is as effective as small-group learning, for midwifery trainees, in augmenting knowledge, thinking, and technical skills addressed in the FIRST course, and have lighter human resource requirements, an important consideration especially in LMIC. However, similar assessments would be needed to assess effectiveness for other digitally delivered clinical education programs. [ABSTRACT FROM AUTHOR]

Introduction- An abnormally positioned placenta is a significant and potentially life-threatening problem for pregnant women. There is ongoing discussion over the early detection and treatment methods to reduce the risk of death and complications. The present study was done to evaluate the role of beta-human chorionic gonadotrophin (B-HCG) level in the first half of pregnancy as a marker for prediction of placenta previa. Material and methods- The present prospective study was conducted among 60 pregnant women who reported to department of obstetrics and gynecology at a tertiary care center during the study period of one year. The study involved sampling all participating mothers between 14 and 18 weeks of gestational age. The results were analyzed using SPSS version 25.0. Results– Out of total 60 women 15 (4%) had condition of placenta previa. The Mean age of patients was 33.45 years, gravid was 4.2, parity was 2.9 and serum hCG was 90,981 IU. Mean serum HCG >104679 iu at 14 weeks of gestation is the ideal cutoff value. The sensitivity and specificity were determined to be 100% and 73.3%, respectively. Conclusion- The measurement of B-HCG levels throughout the first half of pregnancy can serve as an indicator for predicting the occurrence of placenta previa. [ABSTRACT FROM AUTHOR]

BACKGROUND: Season of birth has been associated with age at menarche. Maternal vitamin D levels in pregnancy may explain this effect. We investigated whether the season of first trimester or maternal 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with pubertal timing in children. METHODS: We conducted a follow-up study of 15 819 children born in 2000-03 from the Puberty Cohort, nested in the Danish National Birth Cohort (DNBC). Mean differences in attaining numerous pubertal markers, including a combined estimate for the average age at attaining all pubertal markers, were estimated for low (November-April) relative to high (May-October) sunshine exposure season in the first trimester using multivariable interval-censored regression models. Moreover, we conducted a two-sample instrumental variable analysis using season as an instrument for maternal first-trimester 25(OH)D3 plasma levels obtained from a non-overlapping subset (n = 827) in the DNBC. RESULTS: For the combined estimate, girls and boys of mothers who had their first trimester during November-April had earlier pubertal timing than girls and boys of mothers whose first trimester occurred during May-October: -1.0 months (95% CI: -1.7 to -0.3) and -0.7 months (95% CI: -1.4 to -0.1), respectively. In the instrumental variable analysis, girls and boys also had earlier pubertal timing: respectively, -1.3 months (95% CI: -2.1 to -0.4) and -1.0 months (95% CI: -1.8 to -0.2) per SD (22 nmol/L) decrease in 25(OH)D3. CONCLUSIONS: Both first pregnancy trimester during November-April and lower 25(OH)D3 were associated with earlier pubertal timing in girls and boys.

OBJECTIVE: There is increasing evidence supporting the clinical utility of next generation sequencing for identifying fetal genetic disorders. However, there are limited data on the demand for and accessibility of these tests, as well as payer coverage in the prenatal context. We sought to identify clinician perspectives on the utility of prenatal exome sequencing (ES) and on equitable access to genomic technologies for the care of pregnancies complicated by fetal structural anomalies. METHOD: We conducted two focus group discussions and six interviews with a total of 13 clinicians (11 genetic counselors; 2 Maternal Fetal Medicine/Geneticists) from U.S. academic centers and community clinics. RESULTS: Participants strongly supported ES for prenatal diagnostic testing in pregnancies with fetal structural anomalies. Participants emphasized the value of prenatal ES as an opportunity for a continuum of care before, during, and after a pregnancy, not solely as informing decisions about abortions. Cost and coverage of the test was the main access barrier, and research was the main pathway to access ES in academic centers. CONCLUSION: Further integrating the perspectives of additional key stakeholders are important for understanding clinical utility, developing policies and practices to address access barriers, and assuring equitable provision of prenatal diagnostic testing.

Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural anomalies (FSAs). However, few studies have comprehensively evaluated its performance against current standard-of-care diagnostic tests: karyotype, chromosomal microarray (CMA), and exome sequencing (ES). To assess the clinical utility of GS, we compared its diagnostic yield against these three tests in 1,612 quartet families including an individual with ASD and in 295 prenatal families. Our GS analytic framework identified a diagnostic variant in 7.8% of ASD probands, almost 2-fold more than CMA (4.3%) and 3-fold more than ES (2.7%). However, when we systematically captured copy-number variants (CNVs) from the exome data, the diagnostic yield of ES (7.4%) was brought much closer to, but did not surpass, GS. Similarly, we estimated that GS could achieve an overall diagnostic yield of 46.1% in unselected FSAs, representing a 17.2% increased yield over karyotype, 14.1% over CMA, and 4.1% over ES with CNV calling or 36.1% increase without CNV discovery. Overall, GS provided an added diagnostic yield of 0.4% and 0.8% beyond the combination of all three standard-of-care tests in ASD and FSAs, respectively. This corresponded to nine GS unique diagnostic variants, including sequence variants in exons not captured by ES, structural variants (SVs) inaccessible to existing standard-of-care tests, and SVs where the resolution of GS changed variant classification. Overall, this large-scale evaluation demonstrated that GS significantly outperforms each individual standard-of-care test while also outperforming the combination of all three tests, thus warranting consideration as the first-tier diagnostic approach for the assessment of ASD and FSAs.

Herein, we report an unusual presentation of a 38-year-old heathy lady with a painless slowly growing lesion in the volar aspect of her left distal forearm reaching the thenar area for >15 years. Magnetic resonance imaging of the lesion showed multilobulated soft tissue mass with low and high signal in T1- and T2-weighted images with homogenous contrast enhancement. Additionally, a stable serpiginous bony lesion was noted in the first metacarpal bone showing low T1 and high T2 signals with peripheral enhancement. Histopathological examination was consistent with cylindroma and enchondroma, respectively. The patient had full recovery with no recurrence at a 1-year follow-up visit. While enchondroma is the most common benign tumor of the hand, sporadic dermal cylindroma, in contrast, rarely affects the upper extremity. The coexistence of these two pathological entities was not previously reported and it may complicate the diagnosis. [ABSTRACT FROM AUTHOR]

BackgroundMany health education institutions in African countries such as Nigeria face increasing enrolment of students but lack an adequate number of instructors to train them. If digital learning can be demonstrated effective in augmenting knowledge and skills, this approach could help fill this gap and improve education efficiency. A needs assessment in two Nigerian midwifery schools confirmed that digital learning would be feasible and welcomed. In this study, the Midwifery Active Digitization Empowerment Initiative (MADE-I) program was tested to determine if digital delivery of the Fundamental Interventions, Referral and Safe Transfer (FIRST) course is at least equally effective for training midwifery students compared to conventional small-group delivery.MethodsA non-inferiority randomized controlled trial design was used, enrolling 130 s-year students from 2 midwifery schools in Benue State, Nigeria. Students were randomly assigned into six cohorts. Each cohort received half of the course on a Learning Management Platform on their mobile phones, the other half through standard small-group teaching. Students’ knowledge, thinking, and technical skills were assessed using a pre-test, post-test, Objective Structured Clinical Exam (OSCE), and daily modular quizzes. The data was analyzed using the difference-in-difference method.ResultsThe study revealed that post-intervention student knowledge and thinking skills did not significantly differ between digital learning (75.26%) and small-group learning arms of the trial (75.02%, p = 0.404). Student knowledge improved significantly compared to the pre-test in both groups (by 25.03 points in the digital arm, 26.39, in small-group). Some differences were observed between digital and small-group learning in disaggregated analysis by specific module and midwifery school. Although there was a trend toward small-group learning of technical skills being more effective than digital learning, no significant differences between groups were observed in the post-intervention OSCE. Students in both groups learned equally well regardless of age, gender, and midwifery school entrance exam score.ConclusionDigital learning is as effective as small-group learning, for midwifery trainees, in augmenting knowledge, thinking, and technical skills addressed in the FIRST course, and have lighter human resource requirements, an important consideration especially in LMIC. However, similar assessments would be needed to assess effectiveness for other digitally delivered clinical education programs.

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

BACKGROUND: Prenatal nonessential metals may contribute to postnatal adiposity, whereas essential metals may have metabolic benefits. We evaluated joint and individual associations between prenatal metals and childhood adiposity. METHODS: We measured concentrations of six nonessential (arsenic, barium, cadmium, cesium, lead, and mercury) and four essential (magnesium, manganese, selenium, and zinc) metals in first trimester maternal blood from a prebirth cohort. We collected anthropometric measures in early childhood, mid-childhood, and early adolescence including subscapular+tricep skinfold thickness (mm) (N = 715-859), waist circumference (cm) (N = 717-882), and body mass index (BMI) (z-score) (N = 716-875). We measured adiposity in mid-childhood and early adolescence using bone densitometry total- and trunk- fat mass index (kg/m 2 ) (N = 511-599). We estimated associations using adjusted quantile g-computation and linear regression. RESULTS: The nonessential metal mixture was associated with higher total (β = 0.07, 95% CI = 0.01, 0.12) and trunk fat mass index (β = 0.12, CI = 0.02, 0.22), waist circumference (β = 0.01, CI = 0.00, 0.01), and BMI (β = 0.24, CI = 0.07, 0.41) in mid-childhood, and total fat mass index (β = 0.07, CI = 0.01, 0.14), and BMI (β = 0.19, CI = 0.02, 0.37) in early adolescence. The essential metal mixture was associated with lower early adolescence total-(β = -0.11, CI = -0.17, -0.04) and trunk- fat mass index (β = -0.13, CI = -0.21, -0.05), subscapular+tricep skinfold thickness (β = -0.02, CI = -0.03, -0.00), waist circumference (β = -0.003, CI = -0.01, -0.00), and BMI (β = -0.16, CI = -0.28, -0.04). Cadmium and cesium were individually associated with childhood adiposity at different timepoints. CONCLUSIONS: Prenatal first-trimester essential metals were associated with lower childhood adiposity, whereas nonessential metals were associated with higher adiposity into adolescence.

ObjectivesAnxiety is prevalent in pregnancy and predicts risk of adverse birth outcomes. Many instruments measure anxiety in pregnancy, some of which assess pregnancy anxiety defined as maternal concerns about a current pregnancy (e.g., baby, childbirth). The present study examined covariance among four anxiety or distress measures at two times in pregnancy and tested joint and individual effects on gestational length. We hypothesized that the common variance of the measures in each trimester would predict earlier delivery.MethodResearch staff interviewed 196 women in first and third trimester utilizing a clinical screener of anxiety severity/impairment, two instruments measuring pregnancy anxiety, and one on prenatal distress. Birth outcomes and medical risk factors were obtained from medical records after birth. Structural equation modeling fit latent factors for each trimester from the four measures. Subsequent models tested whether the latent factors predicted gestational length, and unique effects of each measure.ResultsThe third-trimester pregnancy anxiety latent factor predicted shorter gestational length adjusting for mother's age, education, parity, and obstetric risk. Scores on a four-item pregnancy-specific anxiety measure (PSAS) in third trimester added uniquely to prediction of gestational length. In first trimester, scores on the clinical screener (OASIS) uniquely predicted shorter gestational length whereas the latent factor did not.ConclusionThese results support existing evidence indicating that pregnancy anxiety is a reliable risk factor for earlier birth. Findings point to possible screening for clinically significant anxiety symptoms in the first trimester, and pregnancy-specific anxiety thereafter to advance efforts to prevent earlier delivery. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia. Methods We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia in full-term offspring (aged younger than 15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother's age, gestational age, birth order, and child's sex. We analyzed continuous and categorical exposures, estimating odds ratios (ORs) and 95% confidence intervals (CIs) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child's sex. Results N-methyl-perfluorooctane sulfonamidoacetic acid was associated with acute lymphoblastic leukemia in continuous models (per each doubling in levels: ORperlog2 = 1.22, 95% CI = 1.07 to 1.39), with a positive exposure-response across categories (OR>90th percentile = 2.52, 95% CI = 1.33 to 4.78; P trend = .01). Although we found no relationship with perfluorooctane sulfonic acid overall, an association was observed in samples collected in 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2 = 4.01, 95% CI = 1.62 to 9.93). A positive association with perfluorononanoic acid was suggested among first births (P interaction = .06). The N-methyl-perfluorooctane sulfonamidoacetic acid association was mainly limited to children diagnosed before age 5 years (P interaction = .02). We found no consistent patterns of association with other PFAS or differences by sex. Conclusions These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of perfluorooctanesulfonic acid and with a precursor, N-methyl-perfluorooctane sulfonamidoacetic acid. [ABSTRACT FROM AUTHOR]

Neurosurgery is a specialty that has been dominated by males. Although there has been an increase in the number of women in the field, it is not yet close to being equal. Some noteworthy women who have carved the path for other women to follow in their footsteps include Drs. Sofía Ionescu and Diana Beck, the first and second female neurosurgeons worldwide, respectively. However, there are limited publications on Dr. María Cristina García-Sancho, the first Latina neurosurgeon. The purpose of this review was to illuminate the neurosurgical community on the life of Dr. García-Sancho. A thorough literature was performed on medical and non-medical publications that were either authored by Dr. García-Sancho or mentioned her directly. Dr. García-Sancho earned her medical degree at the School of Medicine of the National Autonomous University of Mexico under the guidance of Dr. Clemente Robles, who founded Mexico's first neurosurgical department. Her training took her worldwide. Her expertise allowed her to pioneer a revolutionary advancement known as the one-step bilateral cordotomy. Her perseverance led her to becoming the head of the Department of Neurosurgery at the National Cancer Institute of Mexico and co-found the Mexican Society of Neurological Surgery, where she served on the board of directors. This review aims to advocate for an equitable environment in the field of neurosurgery with Dr. García-Sancho's story. [ABSTRACT FROM AUTHOR]

Background Elevated homocysteine (Hcy) level during pregnancy is positively associated with various gestational-specific diseases. However, there is no uniform standard for the reference interval (RI) of Hcy in pregnancy. Methods From January 2017 to January 2019, 14,530 singleton pregnant women registered at our institute were included for the establishment of trimester-specific RIs of Hcy with both the nonparametric approach and the indirect Hoffmann method, followed by pregnancy outcome association analysis conducted with logistic regression. Results The serum Hcy level in the nonpregnant group was significantly higher than that of pregnant women. A relatively decreased Hcy concentration was observed in the second trimester when compared with that of the first or third trimester. The direct RIs of Hcy in the first or third, and second trimesters were 4.6 to 8.0 mmol/L (merged) and 4.0 to 6.4 mmol/L, respectively, which showed no significant difference compared with the RI derived from the indirect Hoffmann method. In the subsequent risk analysis, the first trimester Hcy was found to be negatively associated with GDM development; whereas the third trimester Hcy conferred increased risk of postpartum hemorrhage after delivery. Conclusion Having established trimester-specific RIs, our study sheds light on the complicated roles of Hcy in pregnancy-related complications. [ABSTRACT FROM AUTHOR]

Aprocitentan (TRYVIO), is the first and only endothelin receptor antagonist for the treatment of high blood pressure not adequately controlled in combination with 3 combined antihypertensive class drugs. Aprocitentan is a dual endothelin receptor antagonist that inhibits the binding of ET-1 to both ETA and ETB receptors. Aprocitentan tablets are available as 12.5 mg orally once daily. It can be administered to subjects with mild and moderate hepatic impairment without the need for dose adjustment. The most frequently reported adverse reactions to during the 4-week double blind placebo-controlled treatment period (part 1) of the PRECISION study is edema and anaemia. Others include embryo-fetal toxicity, hepatotoxicity, fluid retention, hemoglobin decrease, decreased sperm counts. Aprocitentan is contraindicated in pregnancy and in patients who are hypersensitive to aprocitentan or any of its excipients.

Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be due to sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing identified miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n = 113) and parturition (n = 47). Sequencing analysis identified 986 expressed mature miRNAs from female and male placentae at first and third trimester (baseMean>10). Of these, 11 sexually dimorphic (FDR 10, with 508 DE miRNAs in common between female-specific and male-specific analysis (269 upregulated in first trimester, 239 upregulated in third trimester). Of those, miR-4483 had the highest fold changes across gestation. There were 62.5% more female exclusive differences with fold change>2 across gestation than male exclusive (52 miRNAs vs 32 miRNAs), indicating miRNA expression across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex-independent and sex-specific placenta miRNA atlas across gestation, which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences.

Aim: Pediatric lipomas of the head and neck are rarely seen. When reported, they are generally seen as isolated case reports. Here we report an extremely rare type of giant childhood neck lipoma. Background: Lipomas are a group of benign mesenchymal soft tissue tumors formed due to abnormal and excessive proliferation of adipose tissue. They are most common in the age-group of 40-60 years. They are infrequent in the pediatric age-group and rarely occur under the age of 10 years. Case description: A 140 × 80 × 80 mm, 1011 grams lipoma involving both anterior and posterior triangles of the neck with attachments from mastoid process to medial and lateral pterygoids (base of the skull), the substance of submandibular gland, pretracheal fascia and branches of external carotid (posterior auricular artery, occipital artery, and ascending pharyngeal artery) and platysma. The tumor was removed from the neck of 8 years old pediatric patient. Posterior auricular, occipital, and ascending pharyngeal arteries had taken an aberrant route because of the huge mass. The nasopharynx and the entire viscera of the neck were pushed to one side. The mass was adherent to the submandibular gland and in close relation with the lingual nerve. Conclusion: This is the first case report of a giant lipoma of the neck in a pediatric patient which involved both anterior and posterior triangles. To the best of our knowledge, this is the largest neck lipoma reported to date in a child. Clinical significance: Excision of a large neck lipoma should be planned after imaging studies and in a fully equipped operation theater preferably under general anesthesia. Cases of carotid injury and thoracic duct injury have been reported even with utmost precautions and with all modern facilities. [ABSTRACT FROM AUTHOR]

A sufficient vascular network within the feto-maternal interface is necessary for placental function. Several pregnancy abnormalities have been associated with abnormal vascular formations in the placenta. We hypothesized that growth and expansion of the placental vascular network in the equine (Equus caballus) placenta is regulated by estrogens (estrogen family hormones), a hormone with a high circulating concentration during equine gestation. Administration of letrozole, a potent and specific inhibitor of aromatase, during the first trimester (D30 to D118), decreased circulatory estrone sulfate concentrations, increased circulatory testosterone and androstenedione concentrations, and tended to reduce the weight of the fetus (p < 0.1). Moreover, the gene expression of CYP17A1 was increased, and the expression of androgen receptor was decreased in the D120 chorioallantois (CA) of letrozole-treated mares in comparison to that of the control mares. We also found that at D120, the number of vessels tended to decrease in the CAs with letrozole treatment (p = 0.07). In addition, expression of a subset of angiogenic genes, such as ANGPT1, VEGF, and NOS2, were altered in the CAs of letrozole-treated mares. We further demonstrated that 17β-estradiol increases the expression of ANGPT1 and VEGF and increases the angiogenic activity of equine endothelial cells in vitro. Our results from the estrogen-suppressed group demonstrated an impaired placental vascular network, suggesting an estrogen-dependent vasculogenesis in the equine CA during the first trimester.

Uterine rupture following trauma in pregnancy is rare, especially in earlier gestational ages. The diagnosis can be challenging, and treatment may be delayed when patients present with nonspecific findings. Therefore, a high index of suspicion must be maintained. Once diagnosed, the treatment involves surgical exploration. We present a case report of a first-trimester uterine rupture of a twin pregnancy following a motor vehicle collision in a patient with prior cesarean sections. [ABSTRACT FROM AUTHOR]

Medication abortion, also referred to as medical abortion, is a safe and effective method of providing abortion. Medication abortion involves the use of medicines rather than uterine aspiration to induce an abortion. The U.S. Food and Drug Administration (FDA)-approved medication abortion regimen includes mifepristone and misoprostol. The purpose of this document is to provide updated evidence-based guidance on the provision of medication abortion up to 70 days (or 10 weeks) of gestation. Information about medication abortion after 70 days of gestation is provided in other ACOG publications ().

Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal stress years after pregnancy. The 10-item Perceived Stress Scale (PSS) (0-40 range) was completed in the first and third trimesters, and 2-7 years after delivery among a subsample (n = 4161) of nulliparous women enrolled at eight US medical centers between 2010 and 2013 in a prospective, observational cohort study. Demographics, medical history, and presence of APOs (gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preeclampsia (PE), and medically indicated or spontaneous preterm birth (miPTB, sPTB)) were obtained. The associations of prenatal PSS and the presence of APOs with PSS scores years after delivery were estimated using multivariable linear regression. Mean PSS scores were 12.5 (95% CI 12.3, 12.7) and 11.3 (95% CI 11.1, 11.5) in the first and third trimesters respectively and 14.9 (95% CI 14.7, 15.1) 2-7 years later, an average increase of 2.4 points (95% CI 2.2, 2.6) from the start of pregnancy. Regressing PSS scores after delivery on first-trimester PSS and PSS increase through pregnancy showed positive associations, with coefficients (95% CI) of 2.8 (2.7, 3.0) and 1.5 (1.3, 1.7) per 5-point change, respectively. Adding APO indicator variables separately showed higher PSS scores for women with HDP (0.7 [0.1, 1.3]), PE (1.3 [0.6, 2.1]), and miPTB (1.3 [0.2, 2.4]), but not those with GDM or sPTB. In this geographically and demographically diverse sample, prenatal stress and some APOs were positively associated with stress levels 2-7 years after pregnancy.ClinicalTrials.gov Registration number NCT02231398.

Background: Thyroid disorders are one of the commonest endocrine problems among pregnant women. It is often argued that it is not only overt, but subclinical thyroid dysfunction also has similar adverse effects on maternal and fetal outcomes. There is a huge deficiency of data from the Indian population to assess the prevalence of thyroid dysfunction in pregnancy. This study aimed to determine the prevalence of thyroid disorders in pregnancy and their impact on obstetrical outcomes in the Indian population. The study also had the objective of finding a correlation between maternal and fetal thyroid-stimulating hormone (TSH) levels in hypothyroid pregnancies. Materials and Methods: Around 1055 pregnant women in the first and second trimesters were enrolled in the study. A detailed history was noted and general examinations were done. Apart from routine obstetrical investigations, TSH level estimation was done. If the TSH level was deranged, then free T4 (fT4) and free T3 (fT3) levels were also estimated. Furthermore, 50 hypothyroid and euthyroid pregnant women from the same cohort were followed till delivery. Their obstetrical and perinatal outcomes were noted. Results: The prevalence of thyroid dysfunction was 36.5% in this study, which was quite high in the population. Moreover, hypothyroid groups were prone to have pregnancy-induced hypertension (P = 0.03), intrauterine growth restriction (P = 0.05), and preterm delivery (P = 0.04) as compared to control. Cesarean section rate for fetal distress was significantly higher among pregnant hypothyroid women (P = 0.05). Neonatal respiratory distress and low appearance, pulse, grimace, activity, and respiration (APGAR) () scores were significantly more in the hyperthyroidism group (P = 0.04 and P = 0.02, respectively). Maternal TSH was significantly correlated with hemoglobin levels, HbA1c, and systolic blood pressure. Conclusions: Significant adverse effects on maternal and fetal outcomes were seen emphasizing the importance of routine antenatal thyroid screening.

Islam demarcates between permissible and forbidden things to be consumed by humans as food in Quran and Sunnah. The Covid-19 pandemic is also speculated to be caused by the consumption of non-permissible food-items in Islam. In this article a review of Halal (lawful) and Haram (unlawful) foods in the light of Islamic Shariah is given.

OBJECTIVE: Melatonin regulates the mammalian circadian rhythm and plays metabolic functions such as glucose homeostasis. Both melatonin receptors (MTNR1A and MTNR1B, encoded by the MTNR1A and MTNR1B genes, respectively) are expressed in pancreatic beta cells and mediate the glucometabolic roles of melatonin as well as insulin secretion. The MTNR1B gene is a well-known genetic risk factor in type 2 diabetes (T2D); however, little is known about the involvement of the MTNR1A gene in here T2D. We aimed to investigate whether MTNR1A is linked to and/or associated with familial T2D. SUBJECTS AND METHODS: We genotyped 14 single nucleotide polymorphisms within the MTNR1A gene in 212 peninsular Italian families with T2D. We performed parametric linkage and linkage disequilibrium analyses to investigate the role of MTNR1A variants in conferring T2D risk. We considered variants statistically significant if conferring linkage or linkage disequilibrium with p < 0.05. RESULTS: We found 3 novel variants (rs62350392, rs2119883, and rs13147179) significantly linked to and/or associated with T2D in multigenerational Italian families. CONCLUSIONS: This is the first study to report MTNR1A as a novel risk gene in T2D. Functional studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have suggested that age at first birth (AFB) is inversely associated with metabolic diseases, but positively associated with liver cancer in women. Non-alcoholic fatty liver disease (NAFLD) is a canonical example of metabolic dysfunction and inflammation-based liver disease, while the association between AFB and the risk of NAFLD remains unclear. We aimed to investigate the association between AFB and the odds of NAFLD in women. Methods: Women older than 20 years at the time of the survey were analyzed using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018 in the US. AFB was obtained with self-administered questionnaires. NAFLD was diagnosed as fatty liver index (FLI) ≥ 60. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression models. Results: Of the 12,188 women included in this study, 5670 (46.5%) had NAFLD. Compared to individuals with AFB of 30–32 years old (reference group), the fully adjusted ORs and 95% CI in women with AFB < 18, 18–20, 21–23, and 24–26 years were 1.52 (95% CI 1.14, 2.03), 1.60 (95% CI 1.21, 2.11), 1.40 (95% CI 1.06, 1.84), and 1.33 (95% CI 1.01–1.76), respectively. Yet there was no significant difference between AFB of 27–29, 33–35, or > 35 years compared to the reference group. Conclusions: Women with younger AFB have higher odds of NAFLD in later life. Policymakers should consider focusing on those with earlier AFB for screening and prevention of NAFLD. [ABSTRACT FROM AUTHOR]

Background: Spontaneous miscarriage (SM) is the most common complication of pregnancy. Its psychological repercussions are widely documented but few studies have investigated its effect on women’s experience of a subsequent pregnancy. Aim: To evaluate the impact of prior SM on the level of stress experienced by pregnant women during the first trimester of pregnancy. Design and setting: Cross-sectional, observational study, which was conducted between June and October 2021 in France. Method: A self-report questionnaire was distributed to women in the first trimester of pregnancy. Stress was assessed using the Antenatal Perceived Stress Inventory to yield an overall score and a score for three dimensions ('medical and obstetric risks or fetal health'; 'psychosocial changes during pregnancy'; and the ‘prospect of childbirth'). Women with a history of prior SM and those without were compared. Results: In total, 93 women were included; 63 without and 30 with a history of prior SM. Prior SM was not associated with the overall score. The score for the dimension 'medical and obstetric risks or fetal health' was significantly higher in women with prior SM (3.00±0.86 versus 2.34±0.80; β = 0.61 [95% confidence interval {CI} = 0.25 to 0.96]; P = 0.001). Prior SM was significantly associated with the items 'the baby’s health' (P = 0.048) and 'the echography' (P = 0.002). Conclusion: This study shows a significant impact of prior SM on the level of stress of pregnant women during the first trimester, particularly relating to the medical and obstetric risks or fetal health, underlining the need for appropriate psychological support to be provided to women who experience SM. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate outcomes with mifepristone 200 mg orally followed 24-48 h later by misoprostol 800 mcg vaginally for medical abortion at 64-70 days of gestation.Study designWe reviewed electronic databases and medical records for medical abortion cases at 64-70 days' gestation at British Pregnancy Advisory Service clinics in England and Wales from May 2015 through October 2016. Women selected in-office follow-up or self-evaluation of abortion outcome using a checklist along with low-sensitivity urine pregnancy testing. We excluded cases in which we could not locate records and when women did not proceed with medical abortion, did not use misoprostol following mifepristone if abortion had not occurred and did not attend a scheduled follow-up assessment. We analyzed demographic characteristics, treatment outcomes and significant adverse events. We defined treatment success as complete abortion without surgical evacuation and without continuing pregnancy.ResultsOf 2743 cases identified, we could not locate 40 charts and excluded 30 cases, leaving a final sample of 2673. Overall, 2538 (94.9%, 95% CI 94.1-95.8) women had a successful medical abortion. Reasons for failure included continuing pregnancy (n=90, 3.4%, 95% CI 2.7-4.1), retained nonviable pregnancy (n=2, 0.1%, 95% CI 0-0.2) and incomplete abortion (n=43, 1.6%, 95% CI 1.1-2.1). Of those with continuing pregnancies, 81 underwent a uterine aspiration and 9 opted to continue the pregnancy. Thirty-five (1.3%, 95% CI 0.9-1.7) women had significant adverse events; 16 (0.6%, 95% CI 0.3-0.9) underwent an in-hospital aspiration. Pelvic infection (n=4, 0.2%) and transfusion (n=1, 0.03%) occurred rarely.ConclusionMedical abortion from 64 to 70 days with mifepristone and vaginal misoprostol is effective with a low rate of serious adverse events.ImplicationsMedical abortion between 64 and 70 days of gestation may be offered on an outpatient basis using mifepristone and vaginal misoprostol. Service provision without an in-person follow-up is feasible. Not all women with a continuing pregnancy after medical abortion treatment opt to have an aspiration procedure.

PurposeNumerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes.MethodsRetrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal-Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology.ResultsSixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach-Merritt syndrome.ConclusionIn this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.

Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography-tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1-2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1-2% lower estrogen (E1, E2, E3) levels, but 1-2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4-18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1-2% higher (no difference in estrogens). Androgen concentrations were 18-30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.

BackgroundPhthalates are common plasticizer chemicals that have been linked to glucose intolerance in the general population, but there is only limited research on their association with gestational diabetes (GDM).ObjectiveWe evaluated the association between 11 urinary phthalate metabolites and GDM, impaired glucose tolerance (IGT), and continuous blood glucose concentration during pregnancy in The Infant Development and Environment Study (TIDES). Based on prior study results, our primary analyses focused on monoethyl phthalate (MEP) in relation to our outcomes of interest.Study designWe used multi-variable logistic regression to examine the odds of GDM and IGT in relation to an interquartile-range (IQR) increase in natural log (ln)-transformed, specific gravity (SG)-adjusted first trimester (T1) and average of T1 and third trimester (T3) ("T1T3avg") phthalate metabolite concentrations. We fit linear regression models to examine the percent change in blood glucose per IQR increase in ln-transformed, SG-adjusted T1 and T1T3avg phthalates. In sensitivity analyses, we examined interactions between exposure and race. We adjusted for maternal age, maternal body mass index, study center, race/ethnicity, parity, and gestational age at glucose testing.ResultsIn our sample of 705 pregnant women, we observed 60 cases of GDM, 90 cases of IGT, and an average GLT blood glucose of 113.6 ± 27.7 mg/dL. In our primary analysis, T1T3avg MEP was positively associated with GDM ([OR (95% CI) per IQR increase] T1T3avg MEP: 1.61 (1.10, 2.36)). In secondary analyses, most other phthalates were not found to be related to study outcomes, though some associations were noted. Sensitivity analyses indicated possible strong race-specific associations in Asians, though these results are based on a small sample size (n = 35).ConclusionIn alignment with our a priori selection, we documented an association between T1T3avg MEP and GDM. Additional phthalate metabolites were also found to be linked to glucose intolerance, with possible stronger associations in certain racial/ethnic subgroups. Given the prevalence of phthalate exposures and the growing evidence of associations with metabolic outcomes, future studies should continue to examine this question in diverse cohorts of pregnant women, particularly in those who may be at higher risk for GDM and IGT.

BackgroundResidents of Massachusetts and Rhode Island were exposed to tetrachloroethylene-contaminated drinking water from 1968 through the early 1990s when it leached from the vinyl lining of asbestos cement water distribution pipes. While occupational exposure to solvents during pregnancy has consistently been linked to an increased risk of certain birth defects, mixed results have been observed for environmental sources of exposure, including contaminated drinking water. The present case-control study was undertaken to examine further the association between prenatal exposure to tetrachloroethylene-contaminated drinking water and the risk of central nervous system defects, oral clefts and hypospadias.MethodsCases were comprised of live- and stillborn infants delivered between 1968 and 1995 to mothers who resided in 28 Massachusetts and Rhode Island cities and towns with some PCE-contaminated water supplies. Infants with central nervous system defects (N = 268), oral clefts (N = 112) and hypospadias (N = 94) were included. Controls were randomly selected live-born, non-malformed infants who were delivered during the same period and geographic area as cases (N = 771). Vital records and self-administered questionnaires were used to gather identifying information, birth defect diagnoses, and other relevant data. PCE exposure during the first trimester was estimated using water distribution system modeling software that incorporated a leaching and transport model. Prenatal PCE exposure was dichotomized as "high" or "low" exposure at the level corresponding to an estimated average concentration of 40 μg/L, the criterion for remediation when PCE contamination was discovered in 1980.ResultsMothers with "high" levels of exposure to PCE-contaminated drinking water during the first trimester (> 40 μg/L) had increased odds of having a child with spina bifida (OR: 2.0, 95% CI: 0.8-5.4), cleft lip with or without cleft palate (OR: 3.8, 95% CI: 1.2-12.3) and hypospadias (OR: 2.1, 95% CI:0.5-8.3). No increases in the odds of other defects were observed in relation to "high" exposure levels.ConclusionsThe results of the present study suggest that mothers with "high" PCE exposure levels during the first trimester have increased odds of having a child with spina bifida, cleft lip with or without cleft palate, and hypospadias. These findings support several prior studies that observed an increased risk of selected birth defects following prenatal exposure to solvents in occupational and environmental settings. Even though PCE contamination from vinyl lined pipes was remediated many years ago, it remains a widespread contaminant across the U.S and so environmental regulations must be guided by a precautionary perspective that safeguards pregnant women and their offspring.

OBJECTIVE:To investigate if women desire talking to a counselor or physician about contraception when seeking first-trimester medical or surgical abortion. STUDY DESIGN:We conducted a cross-sectional study by distributing self-administered anonymous surveys to women at three clinics in Sacramento, California; Chicago, Illinois; and Cleveland, Ohio, from October 2014 to February 2015. Participants completed surveys after registration and before any in-office counseling. We asked whether women want to discuss contraception, specific topics they want to discuss, reasons why they may not want to talk about contraception and whether they want to receive contraception services as part of their abortion care. We conducted regression analyses to assess associations between patient characteristics and the desire for counseling. RESULTS:Among 3041 eligible women, 1959 (64.4%) completed surveys. Overall, 1208 (61.7%) did not want to discuss contraception prior to having an abortion, primarily citing that they already know which method they want. We found no association between the desire to discuss contraception and age, race, planned abortion method, clinic site and number of unplanned pregnancies. Among those who desired to talk about contraception, subjects preferred to discuss which contraceptive methods are easier to use and more effective as compared to previously used methods. Regardless of their desire for a discussion about contraception, 1386 (70.8%) of subjects wanted to leave the clinic with a specific method, including a long-acting reversible method [intrauterine device or implant (190, 13.7%)] or other hormonal method [pills, patch, ring or injectable (680, 49.1%)]. CONCLUSIONS:The majority of women seeking first-trimester abortion do not come to the clinic wanting to discuss contraception, most commonly because they have a preferred method in mind. IMPLICATIONS:Providers should ask women presenting for abortion if they want to discuss contraception and not assume that they need or desire such information. Focused discussions, starting with the preferred method if known, may better satisfy women's preferences. Providers should account for such desires when allocating resources for contraception services during abortion care.

BackgroundDevelopment of the placenta during the late first trimester is critical to ensure normal growth and development of the fetus. Developmental differences in this window such as sex-specific variation are implicated in later placental disease states, yet gene expression at this time is poorly understood.MethodsRNA-sequencing was performed to characterize the transcriptome of 39 first trimester human placentas using chorionic villi following genetic testing (17 females, 22 males). Gene enrichment analysis was performed to find enriched canonical pathways and gene ontologies in the first trimester. DESeq2 was used to find sexually dimorphic gene expression. Patient demographics were analyzed for sex differences in fetal weight at time of chorionic villus sampling and birth.ResultsRNA-sequencing analyses detected 14,250 expressed genes, with chromosome 19 contributing the greatest proportion (973/2852, 34.1% of chromosome 19 genes) and Y chromosome contributing the least (16/568, 2.8%). Several placenta-enriched genes as well as histone-coding genes were identified to be unique to the first trimester and common to both sexes. Further, we identified 58 genes with significantly different expression between males and females: 25 X-linked, 15 Y-linked, and 18 autosomal genes. Genes that escape X inactivation were highly represented (59.1%) among X-linked genes upregulated in females. Many genes differentially expressed by sex consisted of X/Y gene pairs, suggesting that dosage compensation plays a role in sex differences. These X/Y pairs had roles in parallel, ancient canonical pathways important for eukaryotic cell growth and survival: chromatin modification, transcription, splicing, and translation.ConclusionsThis study is the first characterization of the late first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute to pregnancy outcomes, including fetal growth and birth weight, which was seen in our cohort, with males significantly heavier than females at birth. This transcriptome provides a basis for development of early diagnostic tests of placental function that can indicate overall pregnancy heath, fetal-maternal health, and long-term adult health.

BackgroundPregnancy is associated with improvement in immunoregulation that persists into the geriatric phase. Impaired immunoregulation is implicated in Alzheimer's disease (AD) pathogenesis. Hence, we investigate the relationship between pregnancy and AD.MethodsCross-sectional cohort of British women (N = 95). Cox proportional hazards modeling assessed the putative effects of cumulative months pregnant on AD risk and the mutually adjusted effects of counts of first and third trimesters on AD risk.ResultsCumulative number of months pregnant, was associated with lower AD risk (β = -1.90, exp(β) = 0.15, P = .02). Cumulative number of first trimesters was associated with lower AD risk after adjusting for third trimesters (β = -3.83, exp(β) = 0.02, P < .01), while the latter predictor had no significant effect after adjusting for the former.ConclusionsOur observation that first trimesters (but not third trimesters) conferred protection against AD is more consistent with immunologic effects, which are driven by early gestation, than estrogenic exposures, which are greatest in late gestation. Results may justify future studies with immune biomarkers.

BackgroundThere is a very large population of internal migrants in China, and the majority of migrant women are of childbearing age. Little is known about their utilization of prenatal care and factors that influence this. We examined this using data from a large national survey of migrants.Methods5372 married rural to urban migrant women aged 20-34 who were included in the 2014 National Dynamic Monitoring Survey on Migrants and who delivered a baby within the previous two years were studied. We examined demographic and migration experience predictors of prenatal care in the first trimester and of adequate prenatal visits.Results12.6% of migrant women reported no examination in the first trimester and 27.6% had less than 5 prenatal visits during their latest pregnancy. Multivariate analysis indicated that demographic predictors of delayed and inadequate care included lower educational level, lower income and not having childbearing insurance. Migrating before pregnancy, longer time since migration, having migrated a greater distance, and not returning to their home town for delivery were correlated with better prenatal care.ConclusionsMany internal migrant women in China do not receive adequate prenatal care. While internal migration before pregnancy seems to promote adequate prenatal care, it also creates barriers to receiving care. Strategies to improve prenatal care utilization include expanding access to childbearing insurance and timely education for women before and after they migrate.

BackgroundA significant proportion of newborn and maternal deaths can be prevented through simple and cost-effective strategies. The main aim of this study was to evaluate the impact of the PRONTO obstetric-emergency management training for improving evidence-based birth attendance practices among providers attending the training at 12 hospitals in three states of Mexico from 2010 to 2012, and to estimate dissemination of the training within the hospitals.MethodsThe average treatment on the treated effect of the PRONTO intervention for the probability of performing certain practices during birth attendance was estimated in a sample of 310 health providers. Impact estimates were obtained by performing provider-level matching using a mixed Mahalanobis distance one-to-one nearest-neighbor and exact matching approach. A secondary analysis estimated the positive externalities caused by the intervention in the treated hospitals using the same analytical approach. Provider-level fixed effects regression models were used to estimate the rate of decay of the probability of performing the examined practices.ResultsProviders attending the PRONTO training showed significant increases in the probability of performing the complete active management of the third stage of labor, especially the first and third steps, and skin-to-skin-contact. There was a negative and significant effect on the probability of performing uterine sweeping. Providers who did not attend the training in treated hospitals also showed marked significant changes in the same practices, except for uterine sweeping. There was no evidence of a significant decay of the probability of performing the routine practices over time among the treated providers.ConclusionsPRONTO is efficacious in changing trained providers' behavior, but not on all practices, suggesting that some practices are deeply ingrained. The results also suggest that information on practices is effectively transmitted to peers within treated hospitals. Previous findings of the dilution of the effect of PRONTO on some practices seem to be more related to the rotation of personnel (mainly interns) rather than providers returning to their former habits.Trial registrationNCT01477554 . Registered on November 18, 2011; retrospectively registered.

Objective To develop a pre-pregnancy or first-trimester risk score to identify women at high risk of preterm birth. Study design In this retrospective cohort analysis, the sample was drawn from California singleton livebirths from 2007 to 2012 with linked birth certificate and hospital discharge records. The dataset was divided into a training (2/3 of sample) and a testing (1/3 of sample) set for discovery and validation. Predictive models for preterm birth using pre-pregnancy or first-trimester maternal factors were developed using backward stepwise logistic regression on a training dataset. A risk score for preterm birth was created for each pregnancy using beta-coefficients for each maternal factor remaining in the final multivariable model. Risk score utility was replicated in a testing dataset and by race/ethnicity and payer for prenatal care. Results The sample included 2,339,696 pregnancies divided into training and testing datasets. Twenty-three maternal risk factors were identified including several that were associated with a two or more increased odds of preterm birth (preexisting diabetes, preexisting hypertension, sickle cell anemia, and previous preterm birth). Approximately 40% of women with a risk score ≥ 3.0 in the training and testing samples delivered preterm (40.6% and 40.8%, respectively) compared to 3.1-3.3% of women with a risk score of 0.0 [odds ratio (OR) 13.0, 95% confidence interval (CI) 10.7-15.8, training; OR 12.2, 95% CI 9.4-15.9, testing). Additionally, over 18% of women with a risk score ≥ 3.0 had an adverse outcome other than preterm birth. Conclusion Maternal factors that are identifiable prior to pregnancy or during the first-trimester can be used create a cumulative risk score to identify women at the lowest and highest risk for preterm birth regardless of race/ethnicity or socioeconomic status. Further, we found that this cumulative risk score could also identify women at risk for other adverse outcomes who did not have a preterm birth. The risk score is not an effective screening test, but does identify women at very high risk of a preterm birth.

Nausea and vomiting in pregnancy (NVP) is one of the most common uncomfortable symptoms of women in early pregnancy. A total of 303 Chinese pregnant women from 10 urban cities in their first trimester were recruited in this study to collect their sociodemographic characteristics and their NVP occurrence. Their dietary nutrient and food intakes were also collected by a 24 h dietary recall and a semi-quantitative food frequency questionnaire (SFFQ). Using the univariate analysis and multiple linear regression analysis to estimate the correlation between NVP and dietary intake, we found that 255 (84.1%) pregnant women experienced NVP during their first trimester. The intake of energy, protein, fat, vitamin A, thiamin, riboflavin, vitamin E, phosphorus, potassium, iron and zinc was lower in women with NVP than in those with no NVP. Additionally, women with NVP were more likely to have insufficient intake of protein, riboflavin, calcium, phosphorus and selenium. In terms of specific food groups, the average daily intake of mushrooms, algae, nuts and seeds, meat, eggs and dairy products in the NVP group was lower. Women in the severe NVP group even had insufficient gestational weight gain. We should pay more attention to women who experience nausea and vomiting during pregnancy and provide them with targeted nutritional support. [ABSTRACT FROM AUTHOR]

Freshwater algae (Chlorophyceae-except Zygnematales) were collected from 18 sites (12 springs and 6 streams) in Shaqlawa district within Erbil Province, Kurdistan Region of Iraq from September-2019 to August-2020. Aim of this study isolation and identification new algal species. 27 new algal genera with 40 species records at first time in Kurdistan Region and others provinces of Iraq, which include the following, Scenedesmus considered the most abundance than others algae which seven species identified followed by genus of Chlamydomonas, genus of Chlorophyceae, genus of Characium with three species for each one recorded, but genera Geminella have two species, finally the remaining genera have one species identified for each one. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia.Study designIncluded were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC).ResultsTwenty-five serum biomarkers along with maternal age 80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing).ConclusionTogether with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia.

BackgroundMedical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss.MethodsWe randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 μg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 μg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment.ResultsComplete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group.ConclusionsPretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .).

ObjectiveTo characterize prescription and other medication use in a geographically and ethnically diverse cohort of women in their first pregnancy.MethodsIn a prospective, longitudinal cohort study of nulliparous women followed through pregnancy from the first trimester, medication use was chronicled longitudinally throughout pregnancy. Structured questions and aids were used to capture all medications taken as well as reasons they were taken. Total counts of all medications taken including number in each category and class were captured. Additionally, reasons the medications were taken were recorded. Trends in medications taken across pregnancy and in the first trimester were determined.ResultsOf the 9,546 study participants, 9,272 (97.1%) women took at least one medication during pregnancy with 9,139 (95.7%) taking a medication in the first trimester. Polypharmacy, defined as taking at least five medications, occurred in 2,915 (30.5%) women. Excluding vitamins, supplements, and vaccines, 73.4% of women took a medication during pregnancy with 55.1% taking one in the first trimester. The categories of drugs taken in pregnancy and in the first trimester include the following: gastrointestinal or antiemetic agents (34.3%, 19.5%), antibiotics (25.5%, 12.6%), and analgesics (23.7%, 15.6%, which includes 3.6%; 1.4% taking an opioid pain medication).ConclusionIn this geographically and ethnically diverse cohort of nulliparous pregnant women, medication use was nearly universal and polypharmacy was common.Clinical trial registrationClinicalTrials.gov, NCT01322529.