Contingent screening in stratification of pregnancy care based on risk of pre-eclampsia at 19-24 weeks' gestation.

OBJECTIVE: To explore the possibility of carrying out routine screening for pre-eclampsia (PE) with delivery at < 28, < 32, < 36 weeks' gestation by maternal factors, uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP) in all pregnancies and reserving measurements of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) for only a subgroup of the population. METHODS: This was a prospective observational study in two UK maternity hospitals involving women with singleton pregnancy attending for routine assessment at 19-24 weeks' gestation. The improvement in performance of screening for PE, at fixed risk cut-offs, by the addition of serum PlGF and sFlt-1 to screening by maternal factors, UtA-PI and MAP, was estimated. We examined a policy of contingent screening in which biochemical testing was reserved for only a subgroup of the population. The main outcome measures were the additional contribution of PlGF and sFlt-1 to the performance of screening for PE and the proportion of the population requiring measurement of PlGF and sFlt-1 for maximum performance of screening. RESULTS: The study population included 37 886 singleton pregnancies. At each risk cut-off, the highest detection rates for delivery with PE and the lowest screen-positive rates were achieved in screening with maternal factors, UtA-PI, MAP, PlGF and sFlt-1. The maximum performance by such screening was also achieved by contingent screening in which PlGF and sFlt-1 were measured in only about 40% of the population. CONCLUSION: The performance of screening for PE by a combination of maternal factors, UtA-PI and MAP is improved by measurement of PlGF and sFlt-1 in about 40% of the population. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Stratification of pregnancy care based on risk of pre-eclampsia derived from biophysical and biochemical markers at 19-24 weeks' gestation.

OBJECTIVE: We have proposed previously that all pregnant women should have assessment of risk for pre-eclampsia (PE) at 20 and 36 weeks' gestation and that the 20-week assessment should be used to define subgroups requiring additional monitoring and reassessment at 28 and 32 weeks. The objective of this study was to examine the potential improvement in screening at 19-24 weeks' gestation for PE with delivery at < 28, < 32, < 36 and ≥ 36 weeks' gestation by the addition of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to the combination of maternal demographic characteristics and medical history, uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP). METHODS: This was a prospective, non-intervention study in women attending for an ultrasound scan at 19-24 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at < 36 weeks' gestation were calculated using the competing-risks model to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiples of the median values of UtA-PI, MAP, PlGF and sFlt-1. Different risk cut-offs were used to vary the proportion of the population stratified into each of four risk categories (very high risk, high risk, intermediate risk and low risk) with the intention of detecting about 80%, 85%, 90% and 95% of cases of delivery with PE at < 28, < 32 and < 36 weeks' gestation. The performance of screening was assessed by plotting the detection rate against the screen-positive rate and calculating the areas under these curves, and by the proportion stratified into a given group for fixed detection rates. Model-based estimates of screening performance for these various combinations of markers were also produced. RESULTS: In the study population of 37 886 singleton pregnancies, there were 1130 (3.0%) that subsequently developed PE, including 160 (0.4%) that delivered at < 36 weeks' gestation. In both the modeled and empirical results, there was incremental improvement in the performance of screening with the addition of PlGF and sFlt-1 to the combination of maternal factors, UtA-PI and MAP. If the objective of screening was to identify about 90% of cases of PE with delivery at < 28, < 32 and < 36 weeks and the method of screening was a combination of maternal factors, UtA-PI and MAP, the respective screen-positive rates would be 3.1%, 8.5% and 19.1%. The respective values for screening by maternal factors, UtA-PI, MAP and PlGF were 0.2%, 0.7% and 10.6%, and for screening by maternal factors, UtA-PI, MAP, PlGF and sFlt-1 they were 0.1%, 0.4% and 9.5%. The empirical results were consistent with the modeled results. There was good agreement between the predicted risk and the observed incidence of PE at < 36 weeks' gestation for all three strategies of screening. Prediction of PE at ≥ 36 weeks was poor for all three screening methods, with the detection rate, at a 10% screen-positive rate, ranging from 33.2% to 38.4%. CONCLUSIONS: The performance of screening at 19-24 weeks' gestation for PE with delivery at < 28, < 32 and < 36 weeks' gestation achieved by a combination of maternal demographic characteristics and medical history, UtA-PI and MAP is improved by the addition of serum PlGF and sFlt-1. The performance of screening for PE at ≥ 36 weeks' gestation is poor irrespective of the method of screening at 19-24 weeks. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Women's obstetric history and midtrimester cervical length measurements by 2d/3d and doppler ultrasound / História obstétrica e medida do comprimento do colo uterino de mulheres no segundo trimestre gestacional por ultrassonografia bi/tridimensional e Doppler

Abstract Objective The aim of the present study was to compare the obstetric history and both two- and tri-dimensional ultrasound parameters according to different cervical lengths. Methods The present cross-sectional study analyzed 248 midtrimester pregnant women according to cervical length and compared the data with the obstetric history and 2D/3D ultrasound parameters. Patients were divided into 3 groups according to cervical length: The Short Cervix group for cervical lengths ≥ 15mm and< 25mm(n= 68), the Very Short Cervix group for cervical lengths< 15mm (n = 18) and the Control group, composed of 162 pregnant women with uterine cervical lengths ≥ 25mm. Results When analyzing the obstetric history of only non-nulliparous patients, a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth was reported (p = 0.021). Cervical length and volume were positively correlated (Pearson coefficient = 0.587, p < 0.0001). The flow index (FI) parameter of cervical vascularization was significantly different between the Control and Very Short Cervix groups. However, after linear regression, in the presence of volume information, we found no association between the groups and FI. Uterine artery Doppler was also not related to cervical shortening. Conclusion The present study showed a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth. None of the vascularization indexes correlate with cervical length as an independent parameter. Uterine artery Doppler findings do not correlate with cervical length.

Resumo Objetivo O objetivo do presente estudo foi comparar a história obstétrica e os parâmetros bi- e tridimensionais ultrassonográficos de acordo com os diferentes comprimentos cervicais. Métodos O presente estudo transversal analisou 248 gestantes no segundo trimestre de acordo com o comprimento cervical e comparou os dados com a história obstétrica e os parâmetros ultrassonográficos 2D/3D. As pacientes foram divididas em 3 grupos de acordo com o comprimento do colo uterino: grupo Colo Curto para comprimentos cervicais ≥ 15mm e < 25mm (n = 68), grupo Colo Muito Curto para comprimentos cervicais < 15mm (n = 18) e grupo Controle, composto por 162 gestantes com comprimento cervical uterino ≥ 25 mm. Resultados Ao analisar a história obstétrica apenas de pacientes não nulíparas, foi relatadauma associação significativa entre a presença de colo uterino curto na gravidez atual e pelo menos um episódio de parto prematuro anterior (p = 0,021). Comprimento e volume do colo uterino foram correlacionados positivamente (coeficiente de Pearson = 0,587, p < 0,0001). O parâmetro índice de fluxo (IF) da vascularização cervical foi significativamente diferente entre os grupos Controle e Colo Muito Curto. Entretanto, após regressão linear, na presença de informações de volume, não encontramos associação entre os grupos e o parâmetro IF. Também não foi encontrada relação entre o Doppler da artéria uterina e o encurtamento cervical. Conclusão O presente estudo mostrou uma associação significativa entre a presença de colo uterino curto na gravidez atual e pelo menos um episódio de parto prematuro anterior. Nenhum dos índices de vascularização se correlaciona com o comprimento cervical como parâmetro independente, assim como o Doppler da artéria uterina também não está relacionado ao comprimento do colo uterino.

Women's Obstetric History and Midtrimester Cervical Length Measurements by 2D/3D and Doppler Ultrasound.

OBJECTIVE: The aim of the present study was to compare the obstetric history and both two- and tri-dimensional ultrasound parameters according to different cervical lengths. METHODS: The present cross-sectional study analyzed 248 midtrimester pregnant women according to cervical length and compared the data with the obstetric history and 2D/3D ultrasound parameters. Patients were divided into 3 groups according to cervical length: The Short Cervix group for cervical lengths ≥ 15 mm and < 25 mm (n = 68), the Very Short Cervix group for cervical lengths < 15 mm (n = 18) and the Control group, composed of 162 pregnant women with uterine cervical lengths ≥ 25 mm. RESULTS: When analyzing the obstetric history of only non-nulliparous patients, a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth was reported (p = 0.021). Cervical length and volume were positively correlated (Pearson coefficient = 0.587, p < 0.0001). The flow index (FI) parameter of cervical vascularization was significantly different between the Control and Very Short Cervix groups. However, after linear regression, in the presence of volume information, we found no association between the groups and FI. Uterine artery Doppler was also not related to cervical shortening. CONCLUSION: The present study showed a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth. None of the vascularization indexes correlate with cervical length as an independent parameter. Uterine artery Doppler findings do not correlate with cervical length.

OBJETIVO: O objetivo do presente estudo foi comparar a história obstétrica e os parâmetros bi- e tridimensionais ultrassonográficos de acordo com os diferentes comprimentos cervicais. MéTODOS: O presente estudo transversal analisou 248 gestantes no segundo trimestre de acordo com o comprimento cervical e comparou os dados com a história obstétrica e os parâmetros ultrassonográficos 2D/3D. As pacientes foram divididas em 3 grupos de acordo com o comprimento do colo uterino: grupo Colo Curto para comprimentos cervicais ≥ 15 mm e < 25 mm (n = 68), grupo Colo Muito Curto para comprimentos cervicais < 15 mm (n = 18) e grupo Controle, composto por 162 gestantes com comprimento cervical uterino ≥ 25 mm. RESULTADOS: Ao analisar a história obstétrica apenas de pacientes não nulíparas, foi relatada uma associação significativa entre a presença de colo uterino curto na gravidez atual e pelo menos um episódio de parto prematuro anterior (p = 0,021). Comprimento e volume do colo uterino foram correlacionados positivamente (coeficiente de Pearson = 0,587, p < 0,0001). O parâmetro índice de fluxo (IF) da vascularização cervical foi significativamente diferente entre os grupos Controle e Colo Muito Curto. Entretanto, após regressão linear, na presença de informações de volume, não encontramos associação entre os grupos e o parâmetro IF. Também não foi encontrada relação entre o Doppler da artéria uterina e o encurtamento cervical. CONCLUSãO: O presente estudo mostrou uma associação significativa entre a presença de colo uterino curto na gravidez atual e pelo menos um episódio de parto prematuro anterior. Nenhum dos índices de vascularização se correlaciona com o comprimento cervical como parâmetro independente, assim como o Doppler da artéria uterina também não está relacionado ao comprimento do colo uterino.

Second and third trimester fetal ultrasound population screening for risks of preterm birth and small-size and large-size for gestational age at birth: a population-based prospective cohort study

BACKGROUND: Preterm birth, small size for gestational age (SGA) and large size for gestational age (LGA) at birth are major risk factors for neonatal and long-term morbidity and mortality. It is unclear which periods of pregnancy are optimal for ultrasound screening to identify fetuses at risk of preterm birth, SGA or LGA at birth. We aimed to examine whether single or combined second and third trimester ultrasound in addition to maternal characteristics at the start of pregnancy are optimal to detect fetuses at risk for preterm birth, SGA and LGA. METHODS: In a prospective population-based cohort among 7677 pregnant women, we measured second and third trimester estimated fetal weight (EFW), and uterine artery pulsatility and umbilical artery resistance indices as placenta flow measures. Screen positive was considered as EFW or placenta flow measure < 10th or > 90th percentile. Information about maternal age, body mass index, ethnicity, parity, smoking, fetal sex and birth outcomes was available from questionnaires and medical records. Screening performance was assessed via receiver operating characteristic (ROC) curves and area under the curve (AUC) along with sensitivity at different false-positive rates. RESULTS: Maternal characteristics only and in combination with second trimester EFW had a moderate performance for screening for each adverse birth outcome. Screening performance improved by adding third trimester EFW to the maternal characteristics (AUCs for preterm birth 0.64 (95%CI 0.61 to 0.67); SGA 0.79 (95%CI 0.78 to 0.81); LGA 0.76 (95%CI 0.75; 0.78)). Adding third trimester placenta measures to this model improved only screening for risk of preterm birth (AUC 0.72 (95%CI 0.66 to 0.77) with sensitivity 37% at specificity 90%) and SGA (AUC 0.83 (95%CI 0.81 to 0.86) with sensitivity 55% at specificity 90%). Combining second and third trimester fetal and placental ultrasound did not lead to a better performance as compared to using only third trimester results. CONCLUSIONS: Combining single third trimester fetal and placental ultrasound results with maternal characteristics has the best screening performance for risks of preterm birth, SGA and LGA. As compared to second trimester screening, third trimester screening may double the detection of fetuses at risk of common adverse birth outcomes.

The correlation of fetal cardiac function with gestational diabetes mellitus (GDM) and oxidative stress levels.

Background The primary objective of this study was to compare the fetal cardiac performance index (Tei index) between the fetuses of gestational diabetes mellitus (GDM) mothers and non-GDM mothers; and the secondary objective was to compare various other parameters of fetal cardiac function as well as maternal oxidative stress levels between the groups of GDM and non-GDM mothers. Methods A cross-sectional study was conducted on pregnant women at 24-28 weeks of gestation. All of the participants underwent 100 g, 3-h oral glucose tolerance test (OGTT) as a diagnostic test for GDM and were categorized as non-GDM and GDM group. All participants had fetal echocardiography performed for cardiac function, and then maternal blood samples were collected for biomarker measurements. Results A total of 80 pregnant women, including 43 in the GDM group and 37 in the non-GDM group, were included in the study. The maternal serum 8-isoprostane (8IsoP), tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 levels were significantly higher in the GDM group than those in the non-GDM group (P: 0.028, P: 0.019 and P: 0.031, respectively). The fetal cardiac function parameters were not significantly different between the two groups. Regardless of the GDM status, the fetuses with high levels of oxidative stress (8Isop ≥1000 pg/mg protein) had a significantly higher rate of impaired shortening fraction (SF) of the left ventricle (P: 0.001). Conclusion GDM is significantly associated with an increase in the oxidative stress process, and a high level of oxidative stress was significantly associated with left ventricular (LV) function impairment. Though a correlation between GDM and fetal cardiac function impairment was not clearly demonstrated in this study, this study suggests that GDM patients with a high level of oxidative stress should be evaluated for fetal cardiac function.

Cardiovascular autonomic modulation and baroreflex control in the second trimester of pregnancy: A cross sectional study.

PURPOSE: The aim is to evaluate and characterize cardiovascular autonomic control and baroreflex function and their response to an orthostatic stressor in the second trimester of pregnancy via time, frequency, information and symbolic analyses. METHODS: We evaluated 22 women at 18 weeks of pregnancy, labeled as pregnant group (PG) (30.8±4.4 years), and 22 non-pregnant women (29.8±5.4 years), labeled as control group (CG). Electrocardiogram, non-invasive photoplethysmographic arterial pressure (AP) and respiratory signals were recorded at rest at left lateral decubitus (REST) and during active standing (STAND) for 10 minutes. The heart period (HP) variability and systolic AP (SAP) variability were assessed in the frequency domain. High frequency (HF) and low frequency (LF) spectral indexes were computed. Nonlinear indexes such as symbolic markers (0V%, 1V%, 2LV% and 2UV% indexes), Shannon entropy (SE) and normalized complexity index (NCI) were calculated as well. Baroreflex control was assessed by cross-spectral HP-SAP analysis. We computed baroreflex sensitivity (BRS), HP-SAP squared coherence (K2) and phase in LF and HF bands. RESULTS: At REST, the PG had lower mean, variance and HF power of HP series and lower K2(LF), BRS(LF) and BRS(HF) than the CG. During STAND, CG and PG decreased the mean, CI, NCI and 2UV% and increased 0V% of the HP series and augmented the SAP variance. LFabs of SAP series increased during STAND solely in CG. BRS(HF) was reduced during in both PG and CG, while HFabs of HP series did not diminish during STAND either in PG or CG. Complexity of the autonomic control was similar in PG and CG regardless of the experimental condition. CONCLUSION: We conclude that the second trimester of pregnancy was characterized by a lower parasympathetic modulation and reduced BRS at REST, preserved complexity of cardiac and vascular controls, limited sympathetic response to STAND and general conservation of the baroreflex responses to posture changes. TRIAL REGISTRATION: Begistro Brasileiro de Ensaios clínicos, Number: RBR-9s8t88.

Quantitative anatomy of the primary ossification center in the fetal pubis bone.

PURPOSES: Skeletodysplasiae and hereditary dysostoses constitute a group of over 350 disorders of the skeletal system. Knowledge about development of the pubic primary ossification center may be useful in both determining the fetal stage and maturity, and for detecting congenital disorders. The present study was performed to quantitatively examine the pubic primary ossification center with respect to its linear, planar, and volumetric parameters. MATERIALS AND METHODS: Using methods of computed tomography (CT), digital-image analysis and statistics, the size of the pubic primary ossification center in 33 spontaneously aborted human fetuses (18 males and 15 females) aged 22-30 weeks was studied. RESULTS: With no sex and laterality differences, the best-fit growth dynamics for the pubic primary ossification center was modeled by the following functions: y = - 13.694 + 0.728 × age ± 0.356 for its sagittal diameter, y = - 3.350 + 0.218 × age ± 0.159 for its vertical diameter, y = - 61.415 + 2.828 × age ± 1.519 for its projection surface area, and y = - 65.801 + 3.173 × age ± 2.149 for its volume. CONCLUSIONS: The size of the pubic primary ossification center shows neither sex nor laterality differences. The growth dynamics of the vertical and sagittal diameters, projection surface area, and volume of the pubic ossification centers follow proportionately to fetal age. The obtained numerical findings of the pubic ossification center are considered age-specific reference data with clinical implications in the diagnostics of congenital defects.

Cavernous sinus meningioma presenting as third nerve palsy in pregnancy.

A 33-year-old female patient presented with diplopia and left eye ptosis 26 weeks into her first pregnancy. No investigation was conducted at the time and her symptoms subsided 4 weeks post partum. This same phenomenon occurred during second pregnancy at 20 weeks of gestation, with patient becoming symptom-free again 6 weeks after giving birth. MRI revealed a lesion in the left cavernous sinus in keeping with a meningioma. Due to the surgically challenging location, the lesion was treated with gamma knife radiosurgery. To date, the patient remains asymptomatic with no progression on follow-up imaging 9 years on.

Maternal Serum Concentrations of Corin, Endoglin, PP13, and sFlt-1 and their Changes with Advancement of Pregnancy and Correlation with Doppler of Uterine Arteries.

BACKGROUND: Pre-eclampsia (PE) affects 2% to 5% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. Since PE has complex pathogenesis and treatment is still not found, effective methods for prediction and prevention of PE are still actively searched. AIM: The aim of this study was to find the mean maternal serum concentration of four proteins in Bulgarian pregnant women and to investigate the correlation with uterine artery pulsatility index in the first and second trimester of pregnancy. MATERIALS AND METHODS: In this prospective case-control study, maternal serum concentrations of corin, sEndoglin, PP13, and sFlt-1 were measured, pulsatility index of uterine artery (PI-UA) was assessed in 40 women with Doppler, twice during pregnancy - at the 11th - 13th weeks of gestation and the 20th gestational week. They were randomized in two groups: an experimental group: with increased PIUA at gestational week 13 and a control group: with normal PI-UA. All pregnancies were followed up until the day of delivery and outcomes were recorded. RESULTS: There was no significant difference in the APGAR score and birth weight of the newborns between groups. We found no significant difference in the mean concentration of sEnd, sFlt-1 and PP13 between 11-13 weeks of gestation and 20 week of gestation in the control and experimental groups. Statistically significant difference was found only in the mean concentrations of corin between weeks 11-13 and week 20 in both control (t=3.27; p=0.004) and experimental group (t=3.22; p=0.005). Corin levels and the mean PI of uterine arteries tended to decrease with progression of pregnancy in both groups. CONCLUSIONS: Further prospective studies of larger populations are required to develop a panel of multiple predictors for PE.

Human amniotic fluid stem cells have better potential in early second trimester of pregnancy and can be reprogramed to iPS.

OBJECTIVE: To study the difference of amniotic fluid stem cell potential at different gestational age. MATERIALS AND METHODS: Second trimester amniocentesis was performed during 15 to 22nd week of gestational age in a single medical center from 2015 to 2016. Early second trimester amniotic fluid stem cells (E-AFS) and later one (L-AFS) were defined 15-18th week, and 19-22nd week, respectively. Cell characteristics, surface markers and ability to form induced pluripotent stem cells (iPS) were studied. RESULTS: All the amniotic fluid stem cells samples could be isolated and cultured from second trimester amniocentesis. E-AFS showed more Ckit + cell, shorted doubling time, smaller cell size and higher cell density compared to L-AFS. Both groups had the same stem cell surface markers with highly expression of CD44, CD73, CD90, and CD105, negative for CD45. They can easily be reprogramed into amniotic fluid stem cell derived iPS via standard induction. CONCLUSION: Human amniotic fluid stem cells could be isolated from early or late second trimester amniocentesis with the similar stem cell surface markers presentation, especially in mesenchymal stem cells markers. However, the cells from early second trimester amniocentesis have more Ckit + number and more potential characteristics compared to late second trimester amniocentesis. Both E-AFS and L-AFS could form the iPS easily which lead to the future disease modeling study.

Delayed diagnosis and management of second trimester abdominal pregnancy.

Second trimester abdominal ectopic pregnancies are rare and life threatening. Early diagnosis and treatment are paramount in reducing maternal morbidity and mortality. We describe an unusually late diagnosis of abdominal pregnancy despite multiple ultrasounds beginning in early pregnancy. A 28-year-old G2P1001 sought pregnancy termination at 22 weeks' gestation after fetal anomalies were noted on an 18-week ultrasound during evaluation for elevated maternal serum alfa-fetoprotein. Due to abortion restrictions in her home state, she travelled over 500 miles for abortion care. During dilation and evacuation, suspected uterine perforation led to the finding of a previously undiagnosed abdominal pregnancy. At laparotomy, she underwent left salpingo-oophorectomy and removal of abdominal pregnancy and placenta. A multidisciplinary team approach was paramount in optimising the patient's outcome. Abortion restrictions requiring travel away from the patient's home community interrupted her continuity of care and created additional hardships, complicating management of an unexpected, rare and life-threatening condition.

Surgical Management of the Pregnant Patient With Lumbar Disc Herniation in the Latter Stage of the Second Trimester.

STUDY DESIGN: Case report. OBJECTIVE: To report on a pregnant woman successfully treated with microendoscopic discectomy in the left lateral position under general anesthesia at 24-week gestation. SUMMARY OF BACKGROUND DATA: Treatment for lumbar disc herniation in pregnant women poses a particular challenge due to the complexity of the clinical situation. Review of the literature emphasizes timely diagnosis with adequate management specific for each gestational period. A surgical approach mandates consideration of the physiologic parameters of pregnancy and the effects of these stressors on the fetus. METHODS: A 38-year-old primigravid woman presented with persistent and incapacitating low back and left leg pain. Magnetic resonance imaging demonstrated a herniated disc at L4-5 with a severely compressed left L5 nerve root. Symptoms were resistant to conservative treatment (acetaminophen; 1200 mg/day) and nerve root block with corticosteroids (1 mg/0.5 mL of betamethasone plus 0.5 mL of 1% lidocaine) provided only transient pain relief. Operative management with surgical discectomy was discussed. Anesthesiologists, obstetricians, and neonatologists were consulted for preoperative planning, focusing on appropriate anesthesia, ideal positioning for surgical access, and provision for emergent fetal care. Surgery was ultimately performed in the left lateral position, in contrast to the oft-used prone position. Microendoscopic discectomy was performed under general anesthesia at 24-week gestation. RESULTS: The patient experienced complete relief from pain after surgical intervention and delivered a healthy baby at 39-week gestation after normal labor. Our methods, used in accordance with our preoperative simulation, resulted in a satisfactory outcome for both mother and child. CONCLUSION: Although previously published cases noted the safety of operating in the prone position under epidural anesthesia, we performed minimally invasive microendoscopic discectomy in the left lateral position in combination with general anesthesia and found that this is a safe and preferable alternative for pregnant patients in the latter stage of the second trimester. LEVEL OF EVIDENCE: N/A.

Correlation between maternal serum-amniotic fluid anti-angiogenic factors and uterine artery Doppler indices.

PURPOSE: Elevated sFlt-1 and sEng is usually a clue for impending preeclampsia and intrauterine growth restriction. Likewise, uterine artery Doppler ultrasound is being investigated for prediction of similar conditions. In this study, we aimed to explore the possible relations of these two proteins in different body compartments with uterine artery Doppler indices (UtAD) in a healthy second trimester obstetric population. METHODS: Levels of sFlt-1 and sEng were measured in serum and amniotic fluid samples of 43 patients. UtAD were measured on the days of sample collections. Findings were then analyzed for possible correlation. RESULTS: There was a positive correlation between the levels of maternal serum sFlt-1 (MSsFlt-1) and sEng levels (MSsEng) (r= 0.516, p< 0.001). The negative correlation between MSsFlt-1 and UtAD was disappeared after elimination of poor obstetric outcome pregnancies (r= -0.371, p= 0.016). No correlation was found between UtAD and studied protein levels in amniotic fluid. Mean MSsFlt-1 level was 305.2 ± 220.1 pg/ml and mean AFsFlt-1 was 48.9 ± 11.8 ng/ml. Mean MSsEng level was 4.5 ± 1.3 ng/ml, mean AFsEng level was found 0.7 ± 0.3 ng/ml. Mean values for UtAD were 1.3 ± 0.4, 0.6 ± 0.1 and 3.5 ± 1.3 for PI, RI, and S/D, respectively. CONCLUSION: In normal second trimester pregnancies, there is a positive correlation between serum levels of sFlt-1 and sEng levels. Amniotic fluid levels of sEng and sFlt-1 are not correlated with UtAD in uncomplicated pregnancies.

Estimating drinking-water ingestion and dermal contact with water in a French population of pregnant women: the EDDS cohort study.

The aim of the present study, a part of the Endocrine Disruptor Deux-Sèvres (EDDS) cohort study, was to estimate water-use habits of pregnant French women. The study population consisted of 132 pregnant women living in Deux-Sèvres (France) in 2012-2013, in areas where drinking water is exclusively produced by surface water. Drinking-water data included ingested water (tap, bottled and filtered) and ingestion place (home, work and elsewhere). Dermal contact with water included showering, bathing, swimming, spa use, hand-washing and other water activities. Data were collected through face-to-face interviews at second and third trimesters of pregnancy with a 1-day-recall questionnaire. Intertrimestral differences in water-use habits were assessed. Predictors of water ingestion and duration of dermal contact with water were assessed with multiple linear regressions. At the second trimester of pregnancy, the mean total drinking-water ingestion was 1.8±0.6 l per day (mean and SD), 71% of which was tap water. Total drinking-water ingestion was not different between both trimesters but ingestion place differed. Dermal contact with water estimate was 188±118 and 173±92 min/week at second and third trimesters, respectively. Smoking increased water ingestion 777 ml/day 95% CI (171-1384). Duration of dermal contact in spring was 30 min/week 95% CI (13-48) higher than in winter. Obese women spend 26 min/week 95% CI (2-50) more showering than women with recommended weight. Our estimates of pregnant French women's exposure to water will help researchers to better assess water pollutant risks.

Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

Neural stem/progenitor cells (NSC) have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ) of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS) when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6%) over other sources (range of 0%-27.5%, p<0.004). Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

Intra- and inter-observer variability of evaluation of uterine cervix elastography images during pregnancy.

OBJECTIVES: To evaluate reproducibility and repeatability of the assessment of elastography images of the uterine cervix using an Elastography Index. MATERIAL AND METHODS: Elastography images of the uterine cervix were obtained. Numeric scale called Elastography Index, previously published by the authors, was used to describe parts of the cervix. A total of 282 images were evaluated twice by an experienced and twice by an inexperienced operator RESULTS: Reproducibility and repeatability of the evaluation of internal and external os and cervical canal were over 90%. Inter-assay coefficient of variation was 1.84%, 6.76% and 7.27% respectively and 5.84% for anterior and 16.74% for posterior wall. Analysis of the second evaluation only of both operators revealed no significant difference for posterior wall as well (F-test; p = 0.09). CONCLUSION: Authors proved satisfactory reproducibility and repeatability of subjective assessment of elastography images of uterine cervix during pregnancy with the use of Elastography Index in the hands of experienced and inexperienced observer

A novel three-step approach for predicting the imminent onset of preeclampsia within 4 weeks after blood sampling at 19-31 weeks of gestation.

Our aim was to develop a novel screening method to detect the imminent onset of preeclampsia (PE) within 4 weeks after blood sampling. We prospectively collected data regarding past history of PE/gestational hypertension (GH), blood pressure levels at 16-23 weeks and plasma levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) twice at 19-31 weeks, which were measured using an automated electrochemiluminescence immunoassay. We found that a three-step approach by sequential selection using maternal factors, including a past history of PE/GH or blood pressure levels ≥120/80 mm Hg at 16-23 weeks (first step), followed by plasma levels of PlGF in the <5th percentile (second step) and plasma levels of sFlt-1 in the ≥95th percentile (third step) yielded both high sensitivity and specificity. The imminent onset of PE occurred in 2 of 1199 (0.2%) women recruited at 19-25 weeks and in 6 of 798 (0.8%) women recruited at 26-31 weeks. The sensitivity, specificity, positive likelihood ratio (95% confidence interval), negative likelihood ratio (95% confidence interval), positive predictive value and negative predictive value of the three-step approach for predicting the imminent onset of PE at 19-25 weeks were 100%, 99.8%, 599 (150-2390), 0%, 50% and 100%, respectively; and those at 26-31 weeks were 83%, 99.1%, 94 (42-214), 0.17 (0.03-1.01), 42% and 99.9%, respectively. In conclusion, the three-step approach is a highly sensitive and specific screening method for detecting the imminent onset of PE within 4 weeks after blood sampling at 19-31 weeks of gestation.

The use of digital peripheral artery tonometry to detect endothelial dysfunction in pregnant women who smoke.

OBJECTIVE: We hypothesized that, as has been shown outside of pregnancy, endothelial dysfunction would be seen in a dose-dependent fashion among women who smoke in the midtrimester of pregnancy. STUDY DESIGN: Endothelial function in women with singleton pregnancies between 16 and 23 weeks was analyzed utilizing the Endo-PAT2000 device (Itamar Medical Ltd., Caesarea, Israel) and expressed as a reactive hyperemia ratio (RHI). Serum was drawn to check cotinine and high-sensitivity C-reactive protein (CRP) levels. SAS 9.2 (SAS Institute, Cary, NC) was used to perform statistical tests including Student t test, analysis of variance, Fisher exact test, and Pearson coefficient. RESULTS: Endothelial function was noninvasively examined in 29 smokers and 31 nonsmokers. Demographics including age, race, and parity were similar between groups. Mean RHI was not significantly different between smokers and nonsmokers (1.43 ± 0.32 versus 1.53 ± 0.39, p = 0.27). No correlation was noted when cotinine values were plotted against RHI or CRP values in smokers (rho = 0.24, p = 0.21 and rho = 0.26, p = 0.18, respectively). RHI did correlate with diastolic blood pressure (rho = -0.40, p = 0.002), systolic blood pressure (rho = -0.35, p = 0.006), and heart rate (rho = -0.37, p = 0.004). CONCLUSION: We did not find an association between smoking status and endothelial dysfunction in the midtrimester utilizing a noninvasive methodology.

Ambulatory blood pressure measurements in mid-pregnancy and development of hypertensive pregnancy disorders.

OBJECTIVE: To explore if blood pressure (BP) readings over 24 h is a useful addition to uterine artery Doppler to screen for hypertensive disorders. METHODS: In a prospective observational study, we invited nulliparous women with abnormal and normal uterine artery Doppler but normal BP at the time of their routine anomaly scan. BP was measured by the woman using automated apparatus at five specified time intervals over 24 h at 22-24 weeks. Pregnancy outcome was retrieved from delivery suite records, discharge summaries, and letters to general practitioners if necessary. Logistic regression was used to explore the contribution of uterine artery Doppler and BP measurements towards the development of pre-eclampsia. RESULTS: Data were available from 52 women with abnormal and 48 women with normal uterine artery Doppler. Thirteen women developed hypertension in pregnancy. Significant difference was found in the BP of women who did or did not develop hypertensive disorders. BP recordings showed the diurnal variation. Both uterine artery Doppler mean PI and BP showed significant correlation with future development of hypertension. CONCLUSIONS: Women can self-measure BP at home. BP readings show diurnal variation. There are significant differences in BP of women who do and do not develop hypertension later in the pregnancy. Use of home BP monitoring over 24 h of the day in mid-pregnancy is unlikely to add to the use of uterine artery Doppler and a one-off BP reading for future development of hypertension in pregnancy.