Normal Pregnancy Outcome Research Articles

A control study of artificial oocyte activation in the same period

Objective: To compare the fertility rate and embryo outcome between normal fertilization and the use of Calcium ionophore A23187 on the same period of the same cycle of human ovum for artificial activation. Methods: Patients who conducted the intracytoplasmic sperm injection (ICSI) cycle in vitro fertilization assisted reproductive from January 2015 to December in reproductive center of the Third Affiliated Hospital of Zhengzhou University were enrolled.The protocol of this study was approved by the ethics committee of The Third Affiliated Hospital of Zhengzhou University.The subjects must met at least one of the inclusion criteria: (1)the normal fertilization rate was less than 30% ICSI in the previous ICSI cycle; (2)no good quality embryos in a previous period of third days in ICSI; (3)patients with globozoospermia.The ovum were randomly divided into two groups, control group and artificial oocyte activation (AOA) group. In the control group, the eggs were treated with routine ICSI operation, and the AOA group was activated by A23187 after ICSI. Normal fertilization rate, cleavage rate, pregnancy and birth outcome of two groups were compared. Results: The 2PN fertilization rate in the AOA group 65.93% (60/91) was significantly higher than that in the control group 46.67% (41/89) (P<0.05). In addition, in patients who met the inclusion criteria of 1 categories (2PN≤30%), the 2PN fertilization rate was significantly higher (P<0.05) in the AOA group [79.59% (39/49)] compared with the control group [57.14% (28/49)]. In patients who met the inclusion criteria of 3 categories (globozoospermia), the 2PN fertilization rate was significantly higher (P<0.05) in the AOA group [75% (6/8)] compared with the control group [0% (0/5)]. Conclusions: The use of calcium ionophore A23187 assisted activation could be helpful to improve the normal fertilization rate of ICSI. But the effects of early embryonic development and the safety of generation need to be further studied.

The association between maternal hydronephrosis and acute flank pain during pregnancy: a prospective pilot-study

Purpose: Maternal hydronephrosis may cause flank pain during pregnancy. We aimed to investigate the association between maternal hydronephrosis and flank pain intensity.Methods: From 2014 to 2015, all consecutive women with singleton pregnancies, who presented at our tertiary center due to acute flank pain, were prospectively evaluated by renal ultrasonography and pain questionnaires. A visual analogue scale was used to assess pain intensity. The study had 90% power to detect a significant correlation between hydronephrosis and flank pain (Spearman’s test).Results: A total of 51 consecutive women with left-sided (13.7%), right-sided (64.7%) or bilateral (21.6%) pain were enrolled. The mean gestational age of these women, who presented due to their pain, was 27.5 ± 6.8 weeks at the time of consultation. The mean VAS score was 7.6 ± 2.2. In 43/51 (84.3%) women, hydronephrosis was found on renal sonograms. No correlation was found between the grade of hydronephrosis and pain intensity (p = 0.466; r= −0.28). Women delivered at a mean gestational age of 38.1 ± 2.4 weeks and their infants had a mean birthweight of 3138 ± 677 g.Conclusions: Hydronephrosis is a common finding among pregnant women with acute flank pain. The grade of hydronephrosis does not affect pain intensity. This study suggests normal pregnancy outcomes in these women.

Longitudinal changes of cardiotocographic parameters throughout pregnancy: a prospective cohort study comparing small-for-gestational-age and normal fetuses from 24 to 40 weeks.

To compare longitudinal trends of cardiotocographic (CTG) parameters between small-for-gestational-age (SGA) and normal fetuses, from 24 to 41 weeks of pregnancy. A prospective cohort study was carried out in singleton pregnancies without fetal malformations. At least one CTG was performed in each of the following intervals: 24-26 weeks+6 days, 27-29 weeks+6 days, 30-32 weeks+6 days, 33-35 weeks+6 days, 36-38 weeks+6 days and ≥39 weeks. Tracings were analyzed using the Omniview-SisPorto® 3.6 system. Cases with a normal pregnancy outcome, including a birthweight ≥10th percentile for gestational age, were compared with two groups of SGA fetuses: with birthweight <10th percentile (SGA<p10) and <3rd percentile (SGA<p3; a subgroup of the latter). Generalized linear mixed-effects models were used for analysis. A total of 176 fetuses (31 SGA) and 1256 tracings (207 from SGA fetuses) were evaluated. All CTG parameters changed significantly throughout pregnancy in the three groups, with a decreasing baseline and probability of decelerations, and an increasing average long-term variability (LTV), average short-term variability (STV) and accelerations. Baseline showed a more pronounced decrease (steeper slope) in SGA fetuses, being higher in these cases at earlier gestational ages and lower later in pregnancy. Average LTV was significantly lower in SGA<p3 fetuses, but a parallel increase occurred in all groups. There was a considerable inter-fetal variability within each group. A unique characterization of CTG trends throughout gestation in SGA fetuses was provided. A steeper descent of the baseline was reported for the first time. The findings raise the possibility of clinical application of computerized CTG analysis in screening and management of fetal growth restriction.

Correlation between changes in liver stiffness and preeclampsia as shown by transient elastography

ABSTRACTObjective: The aim of this study was to evaluate the use of Fibroscan as a measure of liver transient elastography in women with preeclampsia and compare the results with a group of normotensive controls. Materials and Methods: In this prospective observational case-control study, women at 24–41 weeks gestation who were diagnosed with preeclampsia using standard criteria, between January 2012 and December 2013, were included. The Fibroscan test was performed by a hepatologist 1–7 days postpartum. A control group consisted of low-risk women with normal pregnancy outcomes. Results: Fibroscan results for fibrosis were significantly higher in the 32 preeclamptic women compared to the 16 normotensive women (mean 4.57 kPa vs. 3.66 kPa respectively, P = 0.01). There was no difference in liver steatosis between women with preeclampsia and normotensive women (226 vs. 225 kPa, respectively, P = 0.442) Conclusions: Fibroscan results for fibrosis were significantly higher in postpartum preeclamptic women (although within the normal range). Further studies are required in order to evaluate the usefulness of Fibroscan as an additional test in the evaluation and management of preeclampsia.

Error-rate estimation in discriminant analysis of non-linear longitudinal data: A comparison of resampling methods.

Consider longitudinal observations across different subjects such that the underlying distribution is determined by a non-linear mixed-effects model. In this context, we look at the misclassification error rate for allocating future subjects using cross-validation, bootstrap algorithms (parametric bootstrap, leave-one-out, .632 and [Formula: see text]), and bootstrap cross-validation (which combines the first two approaches), and conduct a numerical study to compare the performance of the different methods. The simulation and comparisons in this study are motivated by real observations from a pregnancy study in which one of the main objectives is to predict normal versus abnormal pregnancy outcomes based on information gathered at early stages. Since in this type of studies it is not uncommon to have insufficient data to simultaneously solve the classification problem and estimate the misclassification error rate, we put special attention to situations when only a small sample size is available. We discuss how the misclassification error rate estimates may be affected by the sample size in terms of variability and bias, and examine conditions under which the misclassification error rate estimates perform reasonably well.

75 How useful is placental growth factor in routine practice? A clinical evaluation in women presenting with suspected placental disease

Introduction Placental growth factor (PlGF) is increasingly recognised as a marker of placental dysfunction. PlGF for the diagnosis of pre-eclampsia (PE) has recently been recommended by the NICE diagnostic assessment panel to rule out PE within one week but the significance of a positive test remains uncertain. Objectives The aim of this study was to evaluate the use of PlGF in routine practice in women with suspected placental disease with and without features of maternal disease. Methods Women with chronic disease (hypertension, renal disease ± diabetes, n = 114) with a change in maternal condition or women with suspected fetal growth restriction (FGR) (n = 146) had a PlGF performed >20 weeks. Results were revealed and standardised care pathways followed. Outcomes were checked by two independent reviewers. Results In line with previous reports, we observed a much shorter median test-delivery interval in women with a low PlGF Despite a strong association between low PlGF and poor outcome (62% delivered 14 days. 62% (n = 18) of these women had PE and 28% (n = 8) had FGR without maternal disease. There was no significant difference in the test-delivery interval between these groups (13 [0–37] compared with 11 [1–35] days, p > 0.05). There were 2 false positive cases of low PlGF without a diagnosis of PE, however these women had confounding medical comorbidities which made the diagnosis ambiguous. Similarly, 2/77 women had a false positive intermediate PlGFs associated with concurrent maternal disease. There were no normal pregnancy outcomes associated with low PlGF. Evaluation of the 7 false negative cases (a diagnosis of PE with a normal PlGF) demonstrated that none were obtained within a week of delivery (27 [7–63] days). Three of these cases had long test-delivery intervals and 3 cases were complicated by complex maternal disease. Of the women with a normal PlGF and small for gestational age (SGA) (n = 51), the median test-delivery interval was 48 [4–90] days. However, 48/51 (94%) were >7 days before delivery.9/51 of these normotensive SGA pregnancies with normal PlGF were delivered for suspected FGR (abnormal growth velocity, oligohydramnios and/or abnormal Dopplers) and had a median birthweight (BW) centile of 2.8 (0–8–8.3), 17 for suspected SGA (median BW centile 3.6 [0.1–9.6]) and 25 delivered for other reasons (median BW centile 5.25 [1–9.3]). There were 3 cases of stillbirth, one of which had a normal PlGF (23 days before delivery; BW centile 1.4). Conclusion In our cohort, a low PlGF was universally associated with a poor outcome and short test-delivery interval which was not affected by the indication (maternal or fetal) for the PlGF. Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction, however it has highlighted that several evidence gaps remain before this test can be implemented in routine clinical practice and confirms that abnormal PlGF levels in isolation are not an indication for delivery. Further research linking placental pathology and maternal PlGF levels is urgently needed.

Impact of vitamin D deficiency on maternal and birth outcomes in the Saudi population: a cross-sectional study.

BackgroundLow serum vitamin D [25(OH)D] has been associated with different health problems worldwide. However, its causal role in several diseases remains unclear. We aimed to correlate vitamin D status with maternal and neonatal outcomes in pregnant females.MethodOne thousand pregnant women were recruited during early labour from the labour ward of King Khaled University Hospital, Riyadh, Saudi Arabia. Detailed medical data of all participants were collected from their records. Delivery events and birth outcomes were also documented. Serum 25(OH)D levels were measured using an enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve was constructed to evaluate the ability of vitamin D levels to predict complicated pregnancies. Regression analysis was used to test the correlation between serum 25(OH)D levels and different variables.ResultsMost of the participants were Saudis (89.9 %) and housewives (85.1 %) and 86.4 % of them had vitamin D deficiency (mean: 30.46 ± 19.6 nmol/L). Gestational diabetes mellitus (GDM) was the commonest complication detected (11.1 %) while the history of miscarriage was elevated (24.5 %). There was no association between GDM and low 25(OH)D. Yet, there was a significant negative correlation between serum 25(OH)D levels and fasting blood glucose among females older than 35 years (r = −0.2, p = 0.03). Hypertensive disorders of pregnancy and pre-existing hypertension were less than 1.5 % of frequency. Nevertheless, they were only recorded in women with insufficient and deficient vitamin D. ROC curve revealed that 25(OH)D levels were not able to discriminate between normal and adverse pregnancy outcomes (AUROC curve: 0.51; 95 % confidence interval (CI): 0.44–0.58; p = 0.8).ConclusionHypovitaminosis D, a highly prevalent health problem among pregnant females in Riyadh, has no relation to adverse pregnancy outcomes except for a higher prevalence of miscarriage in women with low 25(OH)D.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-0901-4) contains supplementary material, which is available to authorized users.

Imbalance of Amniotic Fluid Activin-A and Follistatin in Intraamniotic Infection, Inflammation, and Preterm Birth.

Microbial invasion of the amniotic fluid (AF) cavity stimulates an inflammatory response that involves activin-A, a pleiotropic mediator member of the TGFβ superfamily involved in connective tissue remodeling. The role of AF follistatin, a natural inhibitor of activin-A, in inflammation-induced preterm birth (PTB), has yet to be determined. The objective of the study was to investigate the relationships between AF activin-A and follistatin in physiological gestation and in pregnancies complicated by PTB and to evaluate a possible role played by the activin-A-follistatin balance in processes leading to PTB and preterm premature rupture of membranes (PPROM). The AF levels of total activin-A and follistatin were immunoassayed in 168 women with a normal pregnancy outcome or PTB with and without intraamniotic inflammation or PPROM. The impact of the activin-A-follistatin imbalance on PTB terminal effector pathways (prostaglandins [prostaglandin E2, prostaglandin F2α] and matrix metalloproteinases [MMP-1, MMP-2, MMP-3, and MMP-9]) was investigated in an amniochorion explant system challenged with lipopolysaccharide (LPS) to mimic inflammation. AF follistatin and the activin-A to follistatin ratio varied with gestational age, both decreasing toward term (P < .001). Activin-A was up-regulated in AF infection (>2-fold elevation in activin-A to follistatin ratio) correlating directly with severity of inflammation (both P < .001). Activin-A increased prostaglandins, MMP-1, and MMP-9 released by amniochorion (P < .05) to LPS-equivalent levels. Follistatin effectively blunted the prostaglandin response to activin-A and LPS and that of MMPs after activin-A but not after LPS challenge. Activin-A and follistatin are part of the complex inflammatory response of the gestational sac to infection and modulate effector pathways leading to PTB. The activin-A to follistatin ratio may play a role in determining the clinical phenotype of PTB as preterm labor or PPROM.

Augmented Expression of Piezo1 in the Uterine Vasculature During Pregnancy

The maternal uterine circulation undergoes expansive remodeling during gestation to facilitate the many‐fold increase in uteroplacental blood flow required for normal pregnancy outcome. Although we and others have shown that endothelial nitric oxide (NO) is a key mediator of this process, the primary molecular sensor responsible for detecting shear stress and transducing it to eNOS activation has yet to be identified. The recent discovery of Piezo1 ‐ a large, mechanically‐activated cation channel that has been implicated in mechanosensing of shear stress in various cell types, including the endothelium, inspired this study. Notably, transfection of Piezo1 into HEK293 cells, which normally cannot sense shear stress, conferred a shear stress responsiveness evidenced by increased cytosolic calcium and eNOS activation. We hypothesized that Piezo1 may be present in uterine arteries, and that its expression would be augmented during pregnancy and linked to increased eNOS.Main uterine arteries (MUA) were collected from adult (12–14 week old) late pregnant (LP: gestational day 20, n=4) Sprague‐Dawley rats, and from age‐matched nonpregnant (NP, n=4) controls. Following euthanization, MUAs were dissected free of surrounding connective and adipose tissues, and cut open to remove any blood present in the lumen. Segments of MUA were either fixed and permeabilized for immunohistochemistry (IHC), or homogenized for Western Blotting (WB). Tissues were incubated with rabbit polyclonal Piezo1 antibody (Ab), eNOS Ab, β‐tubulin Ab; goat anti‐rabbit IgG‐HRP Ab (and/or Alexa Fluor® 488 Ab). Immunolabeled vessels were imaged using a Zeiss LSM 510 META confocal microscope @ 100x; for WB, proteins were detected with chemiluminescent substrate and analyzed using ImageJ software.Results(1) Piezo1 was detected in the MUA of both NP and LP rats (using either method), and localized to the arterial endothelium (IHC). (2) Both Piezo1 and eNOS expression were augmented in MUAs from LP vs. NP rats. Based on this preliminary information, we suggest that Piezo1 may play a role in transducing shear stress into the activation of eNOS in the uterine circulation during pregnancy, and thereby contributes to the expansive arterial remodeling required to maintain sufficient uteroplacental perfusion. This is the first study to identify this channel in uterine vessels, and to show a gestational effect on its expression. As both shear stress and uterine arterial remodeling are attenuated in preeclampsia (a serious gestational disease that afflicts ten million pregnant women worldwide each year), understanding the underlying mechanosensing/transducing mechanisms may lead to new therapeutic strategies for augmenting uteroplacental blood flow.Support or Funding InformationNIH R21 HD080156

The promise of gene therapy.

The promise of gene therapy performed in the preimplantation and prenatal periods of pregnancy is rapidly becoming a reality. New technologies capable of making designed changes in single nucleotides make germline gene therapy possible. The article reviews the ethical and technical challenges of germline gene therapy. Clustered regularly interspaced short palindromic repeats and related technologies are capable of deleting and inserting specific DNA sequences in mutated genes so as to correct the targeted DNA. The ability to target specific gene mutations will offer unique opportunities to at risk families, particularly those whose genotypes prevent any chance of a normal pregnancy outcome. Other applications of gene-modifying technologies on gametes, zygotes, and embryos are likely in the near future. There will be renewed debates on the potentially controversial applications of these technologies because of their capability to genetically alter the human germline and thereby future generations.

High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth, and the source may be the damaged fetal membranes

BackgroundHigh Mobility Group Box-1 (HMGB1) is considered a prototype alarmin molecule. Upon its extracellular release, HMGB1 engages pattern recognition receptors and the Receptor for Advanced Glycation End-products (RAGE) followed by an outpouring of inflammatory cytokines, including interleukin (IL)-6. MethodsWe assayed the amniotic fluid (AF) levels of HMGB1 and IL-6 in 255 women that either had a normal pregnancy outcome or delivered preterm. Immunohistochemistry on fetal membranes was used for cellular localization and validation of immunoassay findings. HMGB1 also was analyzed in amniochorion tissue explants subjected to endotoxin. ResultsAF HMGB1 levels are not gestational age regulated but are increased in women with intra-amniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments. ConclusionsOur research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure to elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth.

Maternal autoantibody profiles at risk for autoimmune congenital heart block: a prospective study in high-risk patients

ObjectiveThis prospective study aimed to identify antibody profiles characterising mothers with fetuses developing congenital heart block (CHB) by comparing their antibody frequencies and levels with those in unaffected mothers.MethodsEighty-one consecutive...

Reduced spontaneous platelet aggregation: a novel risk factor for adverse pregnancy outcome

ObjectiveSpontaneous platelet aggregation has not been adequately assessed as a potential risk factor for adverse outcomes in pregnancy. Therefore the objective of this study was to assess spontaneous platelet aggregation (SPA), measured via a novel functional assay, as a risk factor for hypertensive disease and intra-uterine growth restriction (IUGR). Study designThis was a prospective longitudinal study. Spontaneous platelet aggregation was assessed as a marker of platelet reactivity using a modification of light transmission aggregometry. Platelet reactivity was assessed in four groups: non-pregnant healthy female volunteers (n=30), longitudinally in normal uncomplicated pregnancy (n=50), hypertensive disorder (n=40) and IUGR (n=30). The mean percentage SPA was plotted and compared across all groups. ResultsSpontaneous platelet aggregation was significantly reduced in the first trimester compared to the non-pregnant group (p-value=0.003). The mean aggregation for the hypertensive group was 1.9%, (95% CI −0.08 to 4.02) and for the IUGR group was 1.6%, (95% CI −0.6 to 3.72). Platelet aggregation in the hypertensive group was significantly reduced compared to the normal pregnant group (p<0.05). Spontaneous platelet aggregation was also reduced in the IUGR group compared to normal pregnancy (p<0.05). ConclusionThis study demonstrates that a reduction of spontaneous platelet aggregation may be a novel risk factor for adverse pregnancy outcomes such as pre-eclampsia and IUGR. The most clinically significant finding is that SPA is significantly lower in pregnancies complicated by hypertension and IUGR compared to those who had a normal pregnancy outcome. Further studies should be carried out to asses if spontaneous platelet aggregation may be a clinically useful tool for the prediction of pre-eclampsia and IUGR.

Gender-specific reference charts for cardiotocographic parameters throughout normal pregnancy: a retrospective cross-sectional study of 9701 fetuses

ObjectiveTo establish reference values for cardiotocographic (CTG) parameters from 24 to 41 weeks of gestation in normal pregnancies. Study designRetrospective cross-sectional study, using the first antepartum tracing of singleton fetuses with normal pregnancy outcomes (term birth, normal birthweight, normal umbilical artery pH and Apgar scores, no intensive care unit admission). Cases were consecutively selected from a hospital electronic patient record, and analyzed using the OmniviewSisPorto 3.7 system. Variables were compared between male and female fetuses, by gestational age, and percentile curves were constructed. ResultsA total of 9701 tracings (corresponding to 9701 fetuses) were analyzed. All CTG parameters changed significantly throughout gestation in both genders, with a decrease in baseline and decelerations, and an increase in average long-term variability (LTV), average short-term variability (STV), accelerations and uterine contractions. The mean baseline value decreased 9bpm, and its range almost doubled from 24 to 40 weeks. Until 30 weeks the lower percentiles for average LTV were below 5bpm, and the minimum value for average STV was never below 1bpm. The proportion of tracings without accelerations decreased from 30.1% at 24-25 weeks to 0.5% at 39 weeks. The median number of decelerations was practically zero for all gestational ages. All CTG variables, except decelerations and uterine contractions, showed statistically significant gender differences: baseline was consistently higher in females, while average LTV and average STV tended to be lower in females throughout most of pregnancy. Separate percentile curves were constructed for male and female fetuses. ConclusionThis study provides reference values for CTG parameters throughout pregnancy, derived from the largest dataset of healthy fetuses published to date. For the first time, gender differences were clearly demonstrated in fetal life, and percentile curves constructed separately for male and female fetuses.

Investigation of Nutritional Behaviors in the First and Second Trimesters in Pregnant Women Referring to Clinics in Hamadan, Iran, in 2013.

Background:Pregnancy is a particular period in women’s life that is accompanied by an increase in nutritional needs. Having a normal pregnancy period and successful pregnancy outcomes depends on the intake of sufficient amount of food. The present study aimed to determine nutritional behaviors in pregnant women in the first and second trimesters referring to clinics in Hamadan, Iran.Methods:This cross-sectional study was conducted on 170 women referred to health and treatment centers of Hamadan in 2013. Among Hamadan’s health and treatment centers, 10 were selected as the research setting through cluster sampling. Then, the pregnant women at 8-24 weeks of gestation were randomly entered into the study. The data were collected using nutritional behaviors questionnaire in three months. Accordingly, mean scores below 50, between 50 and 75, and above 75 were considered as weak, moderate, and perfect nutritional behaviors, respectively. The data were analyzed using the SPSS statistical software, version 21 and P<0.05 was considered as statistically significant.Results:The results showed that more than three fourths of the study participants had moderate nutritional behaviors. Insufficient intake of fruit, vegetables, and cereals was detected in 80.6%, 54.1%, and 47.1% of the participants, respectively. Besides, 30% of the women had not used folic acid supplement during their pregnancy period or were not aware of its necessity. The results of multivariate analysis indicated that age was only significantly associated with pregnant women’s score of nutritional behaviors (P=0.010). Additionally, no significant relationship was found between the women’s nutritional behaviors and their strategies for elimination of common pregnancy complications, such as constipation, heartburn, urinary tract infection, and anemia.Discussion and Conclusion:Considering the participants’ moderate nutritional behaviors, health and treatment centers are recommended to provide the necessary training for improving pregnant women’s nutritional behaviors and supervise and follow their execution and evaluation.

Macrophage depletion and TNF-α inhibition prevent resorption in CBA/J × DBA/2 model of CpG-induced abortion

ObjectiveTo elucidate the mechanism by which embryo-resorption was enhanced by pathogenic CpG ODN motif in abortion-prone CBA/J × DBA/2 model and to develop a counter strategy for normal pregnancy outcome. MethodsThis is an animal model-based study. Abortion-prone model is established by CBA/J × DBA/2. An infection was mimicked by CpG ODN injection. ResultsEmbryo-resorption was readily induced by CpG ODN in low doses of CpG ODN (∼25 μg/dam) when intraperitoneally (IP) injected on gestational day(gd) 6.5 in male DBA/2 mated CBA/J female mice. A more modest decline in Progesterone(P4), but not Estrogen(E2) was observed after exposure to CpG ODN in the model. P4 supplement fail to improve pregnancy outcomes, even at pharmocology dose. CpG ODN-induced fetal resorption is prevented by the treatment of anti-F4/80 or by that of anti-TNFα.In the implantation sites, the treatment of anti-F4/80 inhibits the increase both of F4/80+ macrophage proportion and TNF-αexpression level which are induced by CpG ODN. The anti-TNFαtreatment also recovers CpG ODN-induced reduction of CD4+Foxp3+ T cells. ConclusionCirculating P4 is not responsible for the process by which CpG ODN-induced embryonic resorption in an abortion-prone mice. Macrophage depletion and TNF-α inhibition are really noteworthy for CpG ODN-induced pregnancy disruption.

About one-half of early spontaneous preterm deliveries can be identified by a rapid matrix metalloproteinase-8 (MMP-8) bedside test at the time of mid-trimester genetic amniocentesis*

Objective: Mid-trimester amniocentesis continues to be used for the prenatal diagnosis of chromosomal anomalies and other genetic disorders. Analysis of amniotic fluid obtained at the time of mid-trimester genetic amniocentesis identifies those patients who are at risk for early spontaneous preterm delivery. This is based on a solid body of evidence that found subclinical intra-amniotic inflammation/infection to be causally linked to early spontaneous preterm birth. Although several biomarkers have been proposed to identify intra-amniotic inflammation, the accumulated data suggest that the determination of amniotic fluid matrix metalloproteinase-8 (MMP-8), or neutrophil collagenase, is a powerful predictor of spontaneous preterm delivery. MMP-8 is released by inflammatory cells in response to microbial products or “danger signals”. A rapid point-of-care test has been developed to determine MMP-8 at the bedside within 20 min, and without the requirement of laboratory equipment. The objective of this study was to determine whether an elevation of MMP-8 in the amniotic fluid, measured by a rapid point-of-care test, can identify those patients at risk for spontaneous preterm delivery after a mid-trimester genetic amniocentesis. Study design: A case–control study was designed to obtain amniotic fluid from asymptomatic singleton pregnant women who underwent mid-trimester genetic amniocentesis. An MMP-8 bedside test was performed to analyze the amniotic fluid of 64 patients with early spontaneous preterm delivery (<30 weeks) and 128 matched controls with normal pregnancy outcomes. Results: (1) The MMP-8 bedside test (Yoon's MMP-8 Check™) was positive in 42.2% (27/64) of patients with spontaneous preterm delivery but in none (0/128) of the control cases (p < 0.001); (2) the MMP-8 bedside test had a sensitivity of 42.2%, and a specificity of 100% in the prediction of spontaneous preterm delivery (<30 weeks) following a mid-trimester genetic amniocentesis; and (3) among the patients with spontaneous preterm delivery, those with a positive MMP-8 bedside test had a significantly higher rate of spontaneous delivery within 2 weeks and 4 weeks of an amniocentesis [40.7% (11/27) versus 5.4% (2/37); 63.0% (17/27) versus 24.3% (9/37)] and a shorter interval-to-delivery period than those with a negative test [interval-to-delivery: median (range), 16 d (0–95 d) versus 42 d (2–91 d); p < 0.05 for each]. Conclusion: We conclude that 42% of patients with an early spontaneous preterm delivery (< 30 weeks) could be identified by a rapid MMP-8 bedside test at the time of their mid-trimester genetic amniocentesis. The MMP-8 bedside test is a powerful predictor of early spontaneous preterm birth in asymptomatic pregnant women.

Normal Pregnancy Outcome After Transcervical Radiofrequency Ablation of Uterine Fibroids

Normal Pregnancy Outcome After Transcervical Radiofrequency Ablation of Uterine Fibroids

Committee Opinion No. 643: Identification and Referral of Maternal Genetic Conditions in Pregnancy.

Advances in the understanding of genetic conditions, reproductive technologies, and improved medical and surgical care have enabled an increasing number of women with genetic conditions to achieve a normal pregnancy outcome. However, management of certain genetic conditions during pregnancy is complex and may require a multidisciplinary approach from preconception through the postpartum period. Patients with certain genetic conditions, or those at risk of having a particular genetic condition, should have a preconception evaluation with their obstetrician-gynecologists, genetics specialists, maternal-fetal medicine specialists, or other appropriate subspecialists to optimize their care. Given the rarity and complexity of some genetic conditions in pregnancy and their evolving management strategies, a coordinated, multidisciplinary approach to care may provide the best opportunity to improve maternal and fetal outcomes.

Bayesian regression analysis of data with random effects covariates from nonlinear longitudinal measurements.

Joint models for a wide class of response variables and longitudinal measurements consist on a mixed-effects model to fit longitudinal trajectories whose random effects enter as covariates in a generalized linear model for the primary response. They provide a useful way to assess association between these two kinds of data, which in clinical studies are often collected jointly on a series of individuals and may help understanding, for instance, the mechanisms of recovery of a certain disease or the efficacy of a given therapy. When a nonlinear mixed-effects model is used to fit the longitudinal trajectories, the existing estimation strategies based on likelihood approximations have been shown to exhibit some computational efficiency problems (De la Cruz et al., 2011). In this article we consider a Bayesian estimation procedure for the joint model with a nonlinear mixed-effects model for the longitudinal data and a generalized linear model for the primary response. The proposed prior structure allows for the implementation of an MCMC sampler. Moreover, we consider that the errors in the longitudinal model may be correlated. We apply our method to the analysis of hormone levels measured at the early stages of pregnancy that can be used to predict normal versus abnormal pregnancy outcomes. We also conduct a simulation study to assess the importance of modelling correlated errors and quantify the consequences of model misspecification.