Fetal Rhesus Monkey First Trimester Zika Virus Infection Impacts Cortical Development in the Second and Third Trimesters.
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ABSTRACT:
SUBMITTER: Tarantal AF
PROVIDER: S-EPMC8023859 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE: To determine the frequency of diagnostic indications among women seeking to terminate pregnancies for reasons of fetal abnormality, spontaneous fetal demise, or a genetic disorder in a private outpatient clinic specializing in late outpatient abortion procedures. METHOD: A total of 1005 women requested termination of pregnancy for reasons of genetic disorder, fetal anomaly, or fetal demise over 20?years (1992-2012). Gestational ages ranged from 12 to 39?weeks. In all cases, a documented diagnosis of fetal abnormality or fetal demise was made prior to referral. Records were reviewed to verify fetal diagnosis for all patients seeking termination of pregnancy for reasons of fetal disorder. Major complications included major unintended surgery, hemorrhage requiring transfusion, or pelvic infection. RESULTS: Preoperative diagnoses included the following: chromosomal abnormalities (n?=?378), genetic syndromes and single gene disorders (n?=?30), structural anomalies (n?=?494), and other conditions (n?=?103). These include 26 cases of spontaneous fetal demise and nine selective terminations of one abnormal twin. The major complication rate was 0.5%. CONCLUSIONS: The majority of diagnoses were in the categories of genetic disorder and neurologic abnormality.
| S-EPMC4238813 | biostudies-other
Project description:In this study, we aimed to compare the efficiency of non-invasive prenatal testing (NIPT), karyotyping, and chromosomal micro-array (CMA) for the diagnosis of fetal chromosomal anomalies in the second and third trimesters. Pregnant women, who underwent amniocenteses for prenatal genetic diagnoses during their middle and late trimesters, were recruited at the Prenatal Diagnosis Center of Taizhou City. Maternal blood was separated for NIPT, and amniotic fluid cells were cultured for karyotyping and CMA. The diagnostic efficiency of NIPT for detecting fetal imbalanced anomalies was compared with karyotyping and CMA. A total of 69 fetal chromosomal imbalances were confirmed by CMA, 37 were diagnosed by NIPT and 35 were found by karyotyping. The sensitivities of NIPT and karyotyping for diagnosing aneuploidy were 96.3% and 100% respectively. Only one mosaic sexual chromosome monosomy was misdiagnosed by NIPT, whereas the sensitivity of NIPT and karyotyping was 70% and 30%, respectively, for detecting pathogenic deletions and duplications sized from 5-20 Mb. Taken together, our results suggest that the efficiency of NIPT was similar to the formula karyotyping for detecting chromosome imbalance in the second and third trimesters.
| S-EPMC6421281 | biostudies-literature
Project description:Traditional methods of dating a pregnancy based on history or sonographic assessment have a large variation in the third trimester. We aimed to assess the ability of various quantitative measures of brain cortical folding on MR imaging in determining fetal gestational age in the third trimester.We evaluated 8 different quantitative cortical folding measures to predict gestational age in 33 healthy fetuses by using T2-weighted fetal MR imaging. We compared the accuracy of the prediction of gestational age by these cortical folding measures with the accuracy of prediction by brain volume measurement and by a previously reported semiquantitative visual scale of brain maturity. Regression models were constructed, and measurement biases and variances were determined via a cross-validation procedure.The cortical folding measures are accurate in the estimation and prediction of gestational age (mean of the absolute error, 0.43 ± 0.45 weeks) and perform better than (P = .024) brain volume (mean of the absolute error, 0.72 ± 0.61 weeks) or sonography measures (SDs approximately 1.5 weeks, as reported in literature). Prediction accuracy is comparable with that of the semiquantitative visual assessment score (mean, 0.57 ± 0.41 weeks).Quantitative cortical folding measures such as global average curvedness can be an accurate and reliable estimator of gestational age and brain maturity for healthy fetuses in the third trimester and have the potential to be an indicator of brain-growth delays for at-risk fetuses and preterm neonates.
| S-EPMC4940851 | biostudies-literature
Project description:BackgroundInfliximab therapy during pregnancy in inflammatory bowel disease is challenged by a dilemma between maintaining adequate maternal disease control while minimizing fetal infliximab exposure. We investigated the effects of pregnancy on infliximab pharmacokinetics.MethodsThe study population comprised 23 retrospectively identified pregnancies. Patients with inflammatory bowel disease were generally in clinical remission at pregnancy conception (74%) and received steady infliximab maintenance therapy (5 mg/kg q8w n = 17; q6w n = 4; q10w n = 1; 10 mg/kg q8w n = 1). Trough blood samples had been obtained in the same patients prior to pregnancy (n = 119), the first trimester (n = 16), second trimester (n = 18), third trimester (n = 7), and postpregnancy (n = 12). Data were analyzed using nonlinear mixed-effects population pharmacokinetic modeling.ResultsDose-normalized infliximab concentrations were significantly higher during the second trimester (median 15 mg/ml/kg, interquartile range 10-21) compared to prepregnancy (7, 2-12; p = 0.003), the first trimester (9, 1-12; p = 0.04), or postpregnancy (6, interquartile range 3-11; p > 0.05) in patients with inflammatory bowel disease. Similar trends were observed in the third trimester (13, 7-36; p > 0.05). A one-compartment model with linear elimination described the pharmacokinetics of infliximab (volume of distribution n = 18.2 L; clearance 0.61 L/day). Maternal infliximab exposure was influenced by the second and third trimester of pregnancy and anti-infliximab antibodies, and not by pregnancy-imposed physiological changes in, for example, body weight or albumin. Infliximab clearance decreased significantly during the second and third trimesters by up to 15% as compared to pre- and postpregnancy and the first trimester. The increased maternal infliximab exposure was weakly associated with lowered clinical disease activity. Pharmacokinetic model simulations of virtual patients indicated the increased maternal infliximab trough concentrations imposed by pregnancy will not completely counteract the decrease in infliximab concentration if therapy is paused in the third trimester.ConclusionInfliximab clearance decreases significantly in the second and third trimesters, leading to increasing maternal infliximab concentrations in any given regimen. Maternal infliximab levels may thus be maintained as constant in a de-intensified regimen by therapeutic drug monitoring guidance in inflammatory bowel disease.
| S-EPMC8259366 | biostudies-literature
Project description:IntroductionCigarette smoking during pregnancy is associated with poor maternal and child health outcomes. Effective interventions to increase smoking cessation rates are needed particularly for pregnant women unable to quit in their first trimester. Real-time ultrasound feedback focused on potential effects of smoking on the fetus may be an effective treatment adjunct, improving smoking outcomes.MethodsA prospective randomized trial was conducted to evaluate the efficacy of a smoking cessation intervention consisting of personalized feedback during ultrasound plus motivational interviewing-based counseling sessions. Pregnant smokers (N = 360) between 16 and 26 weeks of gestation were randomly assigned to one of three groups: Best Practice (BP) only, Best Practice plus ultrasound feedback (BP+US), or Motivational Interviewing-based counseling plus ultrasound feedback (MI+US). Assessments were conducted at baseline and end of pregnancy (EOP).ResultsAnalyses of cotinine-verified self-reported smoking status at EOP indicated that 10.8% of the BP group was not smoking at EOP; 14.2% in the BP+US condition and 18.3% who received MI+US were abstinent, but differences were not statistically significant. Intervention effects were found conditional upon level of baseline smoking, however. Nearly 34% of light smokers (< or =10 cigarettes/day) in the MI+US condition were abstinent at EOP, followed by 25.8% and 15.6% in the BP+US and BP conditions, respectively. Heavy smokers (>10 cigarettes/day) were notably unaffected by the intervention.DiscussionFuture research should confirm benefit of motivational interviewing plus ultrasound feedback for pregnant light smokers and explore mechanisms of action. Innovative interventions for pregnant women smoking at high levels are sorely needed.
| S-EPMC2711985 | biostudies-literature
Project description:OBJECTIVE:To estimate the risk of adverse perinatal outcomes among women with isolated fetal growth restriction from 17 to 22 weeks of gestation. METHODS:This was a retrospective cohort study of all singleton, nonanomalous pregnancies undergoing ultrasonography to assess fetal anatomy between 17 and 22 weeks of gestation at a single center from 2010 to 2014. After excluding patients with fetal structural malformations, chromosomal abnormalities, or identified infectious etiologies, we compared perinatal outcomes between pregnancies with and without fetal growth restriction, defined as estimated fetal weight less than the 10th percentile for gestational age. Our primary outcome was small for gestational age (SGA) at birth, defined as birth weight less than the 10th percentile. Secondary outcomes included preterm delivery at less than 37 and less than 28 weeks of gestation, preeclampsia, abruption, stillbirth, neonatal death, neonatal intensive care unit admission, intraventricular hemorrhage, need for respiratory support, and necrotizing enterocolitis. RESULTS:Of 12,783 eligible patients, 355 (2.8%) had early second-trimester fetal growth restriction. Risk factors for growth restriction were African American race and tobacco use. Early second-trimester growth restriction was associated with a more than fivefold increase in risk of SGA at birth (36.9% compared with 9.1%, adjusted odds ratio [OR] 5.5, 95% CI 4.3-7.0), stillbirth (2.5% compared with 0.4%, OR 6.2, 95% CI 2.7-12.8), and neonatal death (1.4% compared with 0.3%, OR 5.2, 95% CI 1.6-13.5). Rates of indicated preterm birth at less than 37 weeks of gestation (7.3% compared with 3.3%, OR 2.3, 95% CI 1.5-3.5) and less than 28 weeks of gestation (2.5% compared with 0.2%, OR 10.8, 95% CI 4.5-23.4), neonatal need for respiratory support (16.9% compared with 7.8%, adjusted OR 1.6, 95% CI 1.1-2.2), and necrotizing enterocolitis (1.4% compared with 0.2%, OR 7.7, 95% CI 2.3-20.9) were also significantly higher for those with growth restriction. Rates of preeclampsia, abruption, and other neonatal outcomes were not significantly different. CONCLUSION:Although fetal growth restriction in the early second trimester occurred in less than 3% of our cohort and most of those with isolated growth restriction did not have adverse outcomes, it is a strong risk factor for SGA, stillbirth, neonatal death, and indicated preterm birth.
| S-EPMC5659275 | biostudies-literature
Project description:Background Advanced maternal age is an important parameter associated with increased risk of feto-maternal complications and it is an evolving trend in society for women planning for pregnancy in late ages. However there are no studies done whether advanced maternal age has its effects on expression of growth pattern in the fetus. So this study was done to compare the maternal age with the third trimester fetal biometric parameters. Methods This study was done in 100 antenatal women and divided into two groups: Group 1: optimal maternal age group between 21–29 years of age and Group 2: advanced maternal age 30 and above. The pre-pregnant maternal weight, gestational age and third trimester fetal biometrics using ultrasound are noted and compared between the groups. Results The maternal weight gain between the groups was optimal but the third trimester fetal parameters were significantly less in advanced maternal age. The abdominal circumference in optimal age group and head circumference in advanced maternal age group was closer to calculated estimated date of delivery (EDD) and would be specific in calculating the gestational age. Conclusions Though there is no significant difference in maternal weight gain, there are fetal growth restrictions in advanced maternal age group due to which the third trimester fetal parameters are lesser than the optimal age group. Head circumference would be specific in calculating the estimated date of delivery in advanced maternal age group.
| S-EPMC9867875 | biostudies-literature
Project description:Research on the treatment of second-trimester miscarriages is scarce. We studied the outcomes, and the factors associated with adverse events and need for hospital resources in the medical treatment of second-trimester miscarriage.In these retrospective analyses we studied women treated for spontaneous fetal miscarriage with misoprostol-only (n = 24) or mifepristone and misoprostol (n = 177) in duration of gestation 12+1-21+6. Primary outcomes were the risk factors for surgical evacuation and excessive bleeding. Secondary outcomes were total misoprostol dose, time to expulsion and the length of hospital stay.History of surgical evacuation of the uterus increased the risk of surgical evacuation (p = 0.027). Excessive bleeding was not associated with any of the studied variables. More misoprostol was needed when the duration of gestation exceeded 17+0 weeks (p = 0.036). In multivariate analysis the time to fetal expulsion was shorter in women with history of 1-2 deliveries (hazard ratio [HR] 1.49, 95% confidence interval [CI]; 1.07-2.07), ≥3 deliveries (HR 1.63, 95% CI; 1.11-2.38) and with a two-day interval between mifepristone-misoprostol administration (HR 1.71, 95% CI; 1.05-2.81). Patients with symptoms (i.e. uterine bleeding or pain) at baseline had longer hospital stay (HR 0.66, 95% CI; 0.47-0.92).The factors affecting the outcomes of medical treatment of second-trimester fetal miscarriage are similar to those of second-trimester induced abortion. Two-day interval between mifepristone-misoprostol administration might decrease the time to fetal expulsion and the need of hospital resources.
| S-EPMC5533459 | biostudies-other
Project description:The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease.
| S-EPMC5959775 | biostudies-literature
Project description:In humans, the developmental origins of interneurons in the third trimester of pregnancy and the timing of completion of interneuron neurogenesis have remained unknown. Here, we show that the total and cycling Nkx2.1(+)and Dlx2(+)interneuron progenitors as well as Sox2(+)precursor cells were higher in density in the medial ganglionic eminence (MGE) compared with the lateral ganglionic eminence and cortical ventricular/subventricular zone (VZ/SVZ) of 16-35 gw subjects. The proliferation of these progenitors reduced as a function of gestational age, almost terminating by 35 gw. Proliferating Dlx2(+)cells were higher in density in the caudal ganglionic eminence (CGE) compared with the MGE, and persisted beyond 35 gw. Consistent with these findings, Sox2, Nkx2.1, Dlx2, and Mash1 protein levels were higher in the ganglionic eminences relative to the cortical VZ/SVZ. The density of gamma-aminobutyric acid-positive (GABA(+)) interneurons was higher in the cortical VZ/SVZ relative to MGE, but Nkx2.1 or Dlx2-expressing GABA(+)cells were more dense in the MGE compared with the cortical VZ/SVZ. The data suggest that the MGE and CGE are the primary source of cortical interneurons. Moreover, their generation continues nearly to the end of pregnancy, which may predispose premature infants to neurobehavioral disorders.
| S-EPMC4830297 | biostudies-literature