Ophthalmic artery Doppler in the complementary diagnosis of preeclampsia: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the accuracy of different parameters of the ophthalmic artery Doppler (OAD) in the complementary diagnosis of preeclampsia (PE). METHODS: This meta-analysis adhered to the PRISMA guidelines. To investigate the mean difference in OAD values, peak systolic velocity (PSV), end-diastolic velocity (EDV), second systolic velocity peak (P2), resistance index (RI), pulsatility index (PI), and peak ratio (PR), between PE cases (overall and according to severity) and controls, random-effects meta-analyses were conducted for each Doppler parameter, with overall PE and mild and severe PE subgroups. Diagnostic performance and heterogeneity were evaluated with summary receiver operating characteristic (sROC) curves and 95% confidence intervals obtained with bivariate models. RESULTS: Eight studies stratified the results into mild and severe or late and early PE, involving 1,425 pregnant women. PR and P2 had better diagnostic performance than the other indexes, with the PR of AUsROC at 0.885, the sensitivity of 84%, and specificity of 92%, with a low false-positive rate of 0.08 and the P2 with AUsROC of 0.926, the sensitivity of 85% and specificity of 88%. RI, PI, and EDV showed good performance and consistency across studies but lower AUsROC values of 0.833, 0.794, and 0.772, respectively. CONCLUSION: Ophthalmic artery Doppler is a complementary tool with good performance for the diagnosis of overall and severe preeclampsia, with high and best sensitivity and specificity when using PR and P2 parameters.

Association between cervical length and gestational age at birth in singleton pregnancies: a multicentric prospective cohort study in the Brazilian population.

BACKGROUND: Short cervical length measured during the second trimester of pregnancy is an important risk factor for spontaneous preterm birth (sPTB). The aim of this study is to identify the association between mid-pregnancy cervical length (CL) and gestational age at birth in asymptomatic singleton pregnant women. METHODS: This is a prospective cohort study involving singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial) between July 2015 and March 2019. Transvaginal ultrasound to measure CL was performed from 18 to 22 + 6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks' gestation. For this analysis we considered all women with CL ≤ 30 mm receiving progesterone and a random selection of women with CL > 30 mm, keeping the populational distribution of CL. We obtained prognostic effectiveness data (area under receive operating characteristic curve (AUC), sensitivity and specificity and estimated Kaplan-Meier curves for preterm birth using different CL cutoff points. RESULTS: We report on 3139 women and identified a negative association between cervical length and sPTB. CL ≤ 25 mm was associated with sPTB < 28, sPTB < 34 and sPTB < 37 weeks, whereas a CL 25-30 mm was directly associated with late sPTB. CL by transvaginal ultrasound presented an AUC of 0.82 to predict sPTB < 28 weeks and 0.67 for sPTB < 34 weeks. Almost half of the sPTB occurred in nulliparous women and CL ≤ 30 mm was associated with sPTB at < 37 weeks (OR = 7.84; 95%CI = 5.5-11.1). The number needed to screen to detect one sPTB < 34 weeks in women with CL ≤ 25 mm is 121 and we estimated that 248 screening tests are necessary to prevent one sPTB < 34 weeks using progesterone prophylaxis. CONCLUSIONS: CL measured by transvaginal ultrasound should be used to predict sPTB < 34 weeks. Women with CL ≤ 30 mm are at increased risk for late sPTB.

COVID-19 Vaccines Confer Protection in Hospitalized Pregnant and Postpartum Women with Severe COVID-19: A Retrospective Cohort Study.

The coronavirus disease 2019 (COVID-19) pandemic has had deleterious effects among the obstetric population. Pregnant and postpartum women constitute a high-risk group for severe COVID-19. Vaccination reduces the risk of infection, but it is not known whether women who become infected despite vaccination have a milder course of disease than those who had not been vaccinated. This retrospective cohort study evaluated whether vaccination reduces the severity of COVID-19 infection, as measured by severe maternal morbidity and mortality among hospitalized pregnant and postpartum individuals. A total of 2284 pregnant and postpartum women hospitalized with severe COVID-19 were included. Those who did and who did not receive COVID-19 vaccination were compared. The rates of intensive care unit admission, intubation, and mortality were significantly lower among subjects in the vaccinated group (p < 0.001, p < 0.001 and p < 0.001, respectively). The numbers of patients who needed to be vaccinated to avoid one case of intensive care unit admission, intubation, or death due to COVID-19 were 7, 7, and 9, respectively. The COVID-19 vaccine offers protective effects against intensive care unit admission, intubation, and death in hospitalized pregnant and postpartum women with severe SARS-CoV-2-induced SARS.

Prenatal diagnosis of closed spina bifida: multicenter case series and review of the literature.

Objective: Closed spina bifida (CSB) is an abnormality of the posterior arch formation in which the defect is covered by the skin, without protrusion of nervous tissue. The prenatal diagnosis of CSB is very difficult, rarely diagnosed antenatally.Methods: We present a multicenter case series of six prenatal diagnosis of CSB using two-dimensional (2D) ultrasonography complemented with three-dimensional (3D) ultrasonography and magnetic resonance imaging (MRI). All cases of prenatal diagnosis of CSB were confirmed in the postnatal period/termination of pregnancy by both clinical and/or imaging diagnosis (ultrasonography and MRI).Results: 2D ultrasonography allowed the prenatal diagnosis of six cases. We observed two cases of subcutaneous lipomas, two cases of meningoceles, one case of fibrolipomas, and one case of false-positive CSB (meningomyelocele). 3D ultrasonography using rendering mode was important in one case of meningocele (case# 3). Three cases were delivered at term and one of them was submitted to corrective surgery. All these three newborns were discharged from the hospital well and without neurologic signs. Termination of pregnancy was performed in three cases.Conclusion: During prenatal evaluation, detailed ultrasonographic assessment of the entire spine with the identification of the position and morphology of the conus medullaris and absence of cranial signs of spinal dysraphism are the most valuable sonographic clues for the diagnostic of the CSB.

Prediction of Preterm Birth by Maternal Characteristics and Medical History in the Brazilian Population.

OBJECTIVES: The aim of this study was to assess the performance of a previously published algorithm for first-trimester prediction of spontaneous preterm birth (PTB) in a cohort of Brazilian women. METHODS: This was a retrospective cohort study of women undergoing routine antenatal care. Maternal characteristics and medical history were obtained. The data were inserted in the Fetal Medicine Foundation (FMF) online calculator to estimate the individual risk of PTB. Univariate and multivariate logistic regression analyses were performed to determine the effects of maternal characteristics on the occurrence of PTB. A receiver-operating characteristics (ROC) curve was used to determine the detection rates and false-positive rates of the FMF algorithm in predicting PTB <34 weeks of gestation in our population. RESULTS: In total, 1,323 women were included. Of those, 23 (1.7%) had a spontaneous PTB before 34 weeks of gestation, 87 (6.6%) had a preterm birth between 34 and 37 weeks, and 1,197 (91.7%) had a term delivery. Smoking and a previous history of recurrent PTB between 16 and 30 weeks of gestation without prior term pregnancy were significantly more common among women who delivered before 34 weeks of gestation compared to those who delivered at term were (39.1% vs. 12.0%, p = 0.001 and 8.7% vs. 0%, p < 0.001, respectively). Smoking and history of spontaneous PTB remained significantly associated with spontaneous PTB in the multivariate logistic regression analysis. Significant prediction of PTB <34 weeks of gestation was provided by the FMF algorithm (area under the ROC curve 0.67, 95% CI 0.56-0.78, p = 0.005), but the detection rates for fixed false-positive rates of 10% and 20% were poor (26.1% and 34.8%, respectively). CONCLUSIONS: Maternal characteristics and history in the first trimester can significantly predict the occurrence of spontaneous delivery before 34 weeks of gestation. Although the predictive algorithm performed similarly to previously published data, the detection rates are poor and research on new biomarkers to improve its performance is needed.

The reverse boomerang sign: a marker for first-trimester transposition of great arteries.

OBJECTIVE: To describe a new sonographic marker of transposition of great arteries (TGA) during the first-trimester screening. METHODS: We reviewed six cases of TGA from 2013 to 2016 in which an antenatal diagnosis of TGA at first-trimester screening (11-13 + 6 weeks of gestation) was confirmed postnatally. We specifically assessed images obtained by scanning the fetal heart in three vessels (3V) and three-vessel with trachea (3VT) views using color Doppler. The "reverse boomerang" sign was defined as a reverse curvature of right ventricle outflow tract (RVOT) at level of the 3VT view. RESULTS: We described six cases of confirmed TGA, five singletons and one twin pregnancy, among which only two vessels and the reverse curvature of RVOT (reverse boomerang sign) was demonstrated in the first-trimester screening at level of 3VT view. Ventricular septal defects were observed in three cases, and double outlet right ventricle in one case. No other cardiac or extracardiac anomalies were identified. Termination of pregnancy was not performed in any case. CONCLUSION: Our series case suggests that the reverse boomerang sign may improve the early prenatal screening for TGA.

Association between Dietary Glycemic Index and Excess Weight in Pregnant Women in the First Trimester of Pregnancy.

OBJECTIVE: To assess the association between dietary glycemic index (GI) and excess weight in pregnant women in the first trimester of pregnancy. METHODS: A cross-sectional study in a sample of 217 pregnant women was conducted at the maternal-fetal outpatient clinic of the Hospital Geral de Fortaleza, Fortaleza, state of Ceará, Brazil, for routine ultrasound examinations in the period between 11 and 13 weeks + 6 days of gestation. Weight and height were measured and the gestational body mass index (BMI) was calculated. The women were questioned about their usual body weight prior to the gestation, considering the prepregnancy weight. The dietary GI and the glycemic load (GL) of their diets were calculated and split into tertiles. Analysis of variance (ANOVA) or Kruskal-Walls and chi-squared (χ2) statistical tests were employed. A crude logistic regression model and a model adjusted for confounding variables known to influence biological outcomes were constructed. A p-value < 0.05 was considered significant for all tests employed. RESULTS: The sample group presented a high percentage of prepregnancy and gestational overweight (39.7% and 40.1%, respectively). In the tertile with the higher GI value, there was a lower dietary intake of total fibers (p = 0.005) and of soluble fibers (p = 0.008). In the third tertile, the dietary GI was associated with overweight in pregnant women in the first trimester of gestation, both in the crude model and in the model adjusted for age, total energy intake, and saturated fatty acids. However, this association was not observed in relation to the GL. CONCLUSION: A high dietary GI was associated with excess weight in women in the first trimester of pregnancy.

OBJETIVO: Avaliar a associação entre índice glicêmico (IG) dietético e presença de excesso de peso em gestantes no primeiro trimestre de gestação. MéTODOS: Estudo transversal realizado com 217 gestantes atendidas no Ambulatório de Medicina Materno-Fetal do Hospital Geral de Fortaleza, Fortaleza, CE, para realização de exames ultrassonográficos de rotina no período entre 11 e 13 semanas e 6 dias de gestação. Peso e altura foram obtidos para o cálculo do índice de massa corporal (IMC) gestacional. As mulheres foram questionadas quanto ao peso corporal habitual anterior à gestação, considerado o peso pré-gestacional. O IG e a carga glicêmica (CG) das suas dietas foram calculados e divididos em tercis. As associações foram investigadas por análise de variância (ANOVA, na sigla em inglês) ou pelos testes Kruskal-Walls e qui-quadrado (χ2). RESULTADOS: O grupo tinha alto percentual de excesso de peso pré-gestacional (39,7%) e gestacional (40,1%). Houve menor consumo de fibras totais (p = 0,005) e fibras insolúveis (p = 0,008) no tercil de maior valor de IG. No terceiro tercil, o IG da dieta foi associado ao excesso de peso das mulheres no primeiro trimestre de gestação, tanto no modelo bruto como no modelo ajustado para idade, consumo total de energia e de ácidos graxos saturados. No entanto, não se observou esta associação em relação à CG. CONCLUSãO: O alto IG da dieta consumida foi associado ao excesso de peso das mulheres no primeiro trimestre da gestação.

Second Trimester Screening of Preeclampsia Using Maternal Characteristics and Uterine and Ophthalmic Artery Doppler.

PURPOSE: To establish the performance of a multi-parametric test including maternal risk factors and maternal uterine and ophthalmic artery Doppler in the second trimester of pregnancy for the prediction of preeclampsia (PE). MATERIALS AND METHODS: We performed a prospective observational cohort study with pregnant women who underwent a second trimester morphology scan. Maternal uterine and ophthalmic artery Doppler examinations were performed in 415 singleton pregnancies between 18 and 23 weeks of gestation. Additional history was obtained through participant questionnaires, and follow-up occurred to the time of discharge post-delivery. The control and PE groups were compared to continuous variables using the Kruskal-Wallis test and to categorical variables using the Chi-square and Fisher exact tests. Univariate and multivariate logistic regression analyses were performed to determine the best model for the prediction of PE. RESULTS: 40 (9.6 %) pregnant women developed PE. We observed significant differences in the body mass index (BMI) (p < 0.001), parity (p < 0.001), mean arterial pressure (MAP) (p < 0.001), and pulsatility index (PI) of uterine artery Doppler (p < 0.001) between PE and control groups. The best model for the prediction of PE included maternal characteristics, MAP, maternal uterine and ophthalmic artery Doppler with area under receiver operating characteristics (ROC) curve of 0.710 (95 % confidence interval, 613 - 0.807) with a sensitivity of 45 % to a false-positive rate of 10 % and 35 % to a false-positive rate of 5 %. CONCLUSION: Maternal ophthalmic artery Doppler did not promote a significant increase in the PE detection rate during the second trimester scan.

Comparison of three algorithms for prediction preeclampsia in the first trimester of pregnancy.

OBJECTIVE: To compare a new simple algorithm for preeclampsia (PE) prediction among Brazilian women with two international guidelines - National Institute for Clinical Excellence (NICE) and American College of Obstetricians and Gynecologists (ACOG). METHODS: We performed a secondary analysis of two prospective cohort studies to predict PE between 11 and 13+6weeks of gestation, developed between August 2009 and January 2014. Outcomes measured were total PE, early PE (<34weeks), preterm PE (<37weeks), and term PE (≥37weeks). The predictive accuracy of the models was assessed using the area under the receiver operator characteristic curve (AUC-ROC) and via calculation of sensitivity and specificity for each outcome. RESULTS: Of a total of 733 patients, 55 patients developed PE, 12 at early, 21 at preterm and 34 at term. The AUC-ROC values were low, which compromised the accuracy of NICE (AUC-ROC: 0.657) and ACOG (AUC-ROC: 0.562) algorithms for preterm PE prediction in the Brazilian population. The best predictive model for preterm PE included maternal factors (MF) and mean arterial pressure (MAP) (AUC-ROC: 0.842), with a statistically significant difference compared with ACOG (p<0.0001) and NICE (p=0.0002) guidelines. CONCLUSION: The predictive accuracies of NICE and ACOG guidelines to predict preterm PE were low and a simple algorithm involving maternal factors and MAP performed better for the Brazilian population.

Simple approach based on maternal characteristics and mean arterial pressure for the prediction of preeclampsia in the first trimester of pregnancy.

AIM: To propose a simple model for predicting preeclampsia (PE) in the 1st trimester of pregnancy on the basis of maternal characteristics (MC) and mean arterial pressure (MAP). METHODS: A prospective cohort was performed to predict PE between 11 and 13+6 weeks of gestation. The MC evaluated were maternal age, skin color, parity, previous PE, smoking, family history of PE, hypertension, diabetes mellitus and body mass index (BMI). Mean arterial blood pressure (MAP) was measured at the time of the 1st trimester ultrasound. The outcome measures were the incidences of total PE, preterm PE (delivery <37 weeks) and term PE (delivery ≥37 weeks). We performed logistic regression analysis to determine which factors made significant contributions for the prediction of the three outcomes. RESULTS: We analyzed 733 pregnant women; 55 developed PE, 21 of those developed preterm PE and 34 term PE. For total PE, the best model was MC+MAP, which had an area under the receiver operating characteristic curve (AUC ROC) of 0.79 [95% confidence interval (CI)=0.76-0.82]. For preterm PE, the best model was MC+MAP, with an AUC ROC of 0.84 (95% CI=0.81-0.87). For term PE, the best model was MC, with an AUC ROC of 0.75 (0.72-0.79). The MC+MAP model demonstrated a detection rate of 67% cases of preterm PE, with a false-positive rate of 10%, positive predictive value of 17% and negative predictive value of 99%. CONCLUSION: The MC+MAP model showed good accuracy in predicting preterm PE in the 1st trimester of gestation.

Lymphocyte immunotherapy in the treatment of recurrent miscarriage: systematic review and meta-analysis.

PURPOSE: Recurrent miscarriage (RM) affects up to 2-3% of couples of reproductive age. There are several causes for this condition, including immunologic. The embryo is considered an allograft, subject to the rejection mechanisms of the maternal immune system. Immunotherapy involving immunization with lymphocytes is considered in cases of idiopathic RM. However, there is still no consensus regarding the efficacy and safety of this therapy. METHODS: This systematic review and meta-analysis evaluated the data available in the literature regarding the efficacy and safety of the use of immunotherapy with lymphocytes in couples with history of RM. Searches in PubMed/Medline, SCOPUS, and Cochrane Library databases were conducted, using the following keywords: "recurrent miscarriage," "lymphocyte immunotherapy," and "meta-analysis." Statistical analyses were performed using Review Manager 5.3 (RevMan), version 5.3. RESULTS: Six published meta-analysis were retrieved; two found no improvements in the rate of live births after the use of immunization with lymphocytes in the treatment of RM, and four found a beneficial effect of the use of immunotherapy with lymphocytes in cases of RM, with significant improvements in the rate of live births. CONCLUSION: Data available in the literature supports the efficacy and safety of immunotherapy with lymphocytes in cases of RM without an identified cause.

Renal Interlobar Vein Impedance Index as a First-Trimester Marker Does Not Predict Hypertensive Disorders of Pregnancy.

OBJECTIVES: The purpose of this study was to examine whether the maternal renal interlobar vein impedance index as assessed by first-trimester sonography is able to predict the later development of hypertensive disorders of pregnancy. METHODS: Venous Doppler parameters of both maternal kidneys were studied in 214 pregnant women at gestational ages of 11 weeks to 13 weeks 6 days. Patients were classified according to outcomes related to hypertensive disorders. Detection rates and areas under receiver operating characteristic curves were determined for the maternal renal interlobar vein impedance index as a first-trimester predictor of preeclampsia and gestational hypertension. RESULTS: Among the 214 patients, 22 (10.3%) developed preeclampsia; 10 (4.7%) developed gestational hypertension; and 182 were unaffected by hypertensive disorders (controls; 85.0%). In the overall study population, there was no difference in the impedance index between the right (0.44; 95% confidence interval, 0.35-0.50) and left (0.43; 95% confidence interval, 0.35-0.53) sides (P = .86). The average impedance index did not differ among women destined to develop preeclampsia (0.46; 95% confidence interval, 0.38-0.57), gestational hypertension (0.39; 95% confidence interval, 0.33-0.46), or pregnancies uncomplicated by hypertensive disease (0.42; 95% confidence interval, 0.37-0.50; P = .15). Low detection rates and the area under the curve analysis demonstrated that the impedance index was not predictive of hypertensive disorders of pregnancy. CONCLUSIONS: The maternal renal interlobar vein impedance index should not be considered a first-trimester marker of hypertensive disorders of pregnancy.

Maternal uterine artery Doppler in the first and second trimesters as screening method for hypertensive disorders and adverse perinatal outcomes in low-risk pregnancies.

OBJECTIVE: To assess the maternal demographic characteristics and uterine artery (UA) Doppler parameters at first and second trimesters of pregnancy as predictors for hypertensive disorders (HDs) and adverse perinatal outcomes. METHODS: This prospective cohort study comprised 162 singleton low-risk women undergoing routine antenatal care. The left and right UA were assessed by color and pulsed Doppler and the mean pulsatility and resistance indices as well as the presence of a bilateral protodiastolic notch were recorded at 11 to 14 and 20 to 24 weeks' gestation. Multilevel regression analysis was used to determine the effects of maternal characteristics and abnormal UA Doppler parameters on the incidence of HD, small for gestational age newborn, cesarean section rate, Apgar score <7 at 1st and 5th minute, and admission to the neonatal intensive care unit. RESULTS: Fifteen women (9.2%) developed HD. UA mean resistance index (RI), UA mean pulsatility index, and parity were independent predictors of HD. Compared to the pregnancies with a normal UA mean RI at the first and second trimesters, pregnancies with UA mean RI >95th percentile only at the first trimester showed an increased risk for HD (odds ratio, 23.25; 95% confidence interval, 3.47 to 155.73; P<0.01). Similar result was found for UA mean pulsatility index >95th percentile (odds ratio, 9.84; 95% confidence interval, 1.05 to 92.10; P=0.05). The model including maternal age, maternal and paternal ethnicity, occupation, parity and UA mean RI increased the relative risk for HD (area under receiver operating characteristics, 0.81). CONCLUSION: A first-trimester screening combining maternal characteristics and UA Doppler parameters is useful to predict HD in a low-risk population.

Brachial artery flow mediated dilation and pulsatility index change as independent predictors for hypertensive disorders in the second trimester of pregnancy.

OBJECTIVE: To assess brachial artery flow mediated dilatation (FMD) and pulsatility index change (PIC) as independent parameters for prediction hypertensive disorders (preeclampsia - PE and gestational hypertension - GH) in the second trimester of pregnancy. STUDY DESIGN: We performed a prospective cohort study with 372 singleton pregnant women who underwent routine second trimester morphology scan. FMD and PIC were measured immediately after the ultrasound scan using the following formulas: FMD (%)=[(post occlusion arterial diameter-baseline arterial diameter)/baseline arterial diameter]×100 and PIC (%)=[(pulsatility index pre-pulsatility index post)/pulsatility index pre]. The control and hypertensive disorder groups were compared using the Kruskal-Wallis to continue variables and Chi-square and Fisher exact tests to categorical variables. We assessed the predictive accuracy of FMD and PIC by the area under the receiver operating characteristics (ROC) curve with its respective 95% confidence interval (CI). RESULTS: We did not observe statistical difference between control and hypertensive disorder groups regarding the FMD and PIC (p=0.17 and p=0.38, respectively). Areas under ROC curve for prediction of GH using FMD and PIC were 0.59 (CI95% 0.48-0.71) and 0.60 (CI95% 0.47-0.73), respectively. Areas under ROC curve for prediction of PE using FMD and PIC were 0.55 (CI95% 0.46-0.64) and 0.52 (CI95% 0.61-0.69), respectively. CONCLUSION: Brachial artery FMD and PIC as independent parameters did not show good prediction for hypertensive disorders in the second trimester of pregnancy.

Unconditional reference values for the amniotic fluid index measurement between 26w0d and 41w6d of gestation in low-risk pregnancies.

OBJECTIVE: To establish reference values for the amniotic fluid index (AFI) measurement between 26w0d and 41w6d of gestation in a Brazilian population. METHODS: We performed a cross-sectional study with 1984 low-risk singleton pregnant women between 26w0d and 41w6d of gestation. AFI was measured according to the technique proposed by Phelan et al. Maternal abdomen was divided into four quadrants using the umbilicus and linea nigra as landmarks. Single vertical pocket in each quadrant was measured and the AFI was generated by the sum of these four values without umbilical cord or fetal parts. All ultrasound exams were performed by only two experienced examiners. AFI was expressed as median, interquartile range, mean and ranges in each gestational age (GA) interval. Polynomial regressions were performed to obtain the best fit with adjustment by the determination coefficient (R(2)). RESULTS: Mean of AFI ranged from 14.0 ± 4.1 cm (range, 9.7-14.0) at 26w0d to 8.3 ± 4.7 cm (range, 1.9-16.5) at 41w6d, respectively. The best polynomial regression fit curve was a first-degree: AFI = 16.29-0.125*GA (R(2) = 0.01). According the scatterplot, AFI values practically did not vary with advancing GA. CONCLUSION: Reference values for the AFI measurement between 26w0d and 41w6d of gestation in a low-risk Brazilian population were established.

Assessment of angiogenesis modulators in pregnant women with pre-eclampsia: a case-control study.

PURPOSE: This study aimed to evaluate the serum concentration of factors associated with placental angiogenesis in pre-eclamptic and normotensive pregnant women. METHODS: This was a prospective, cross-sectional, case-control study in which the pro-angiogenic factors PlGF, VEGF and IL-10, and the anti-angiogenic factors IL-6, IL-17 and TNF-α of 55 pregnant women (31 with pre-eclampsia-PE and 24 normotensive), with gestational age ≥20 weeks, were measured in maternal blood through the enzyme-linked immunosorbent assay (ELISA). The Mann-Whitney and Kruskal-Wallis tests were used for comparison between groups. RESULTS: Serum PIGF was reduced in the group of pregnant women with PE when compared with the normotensive women (493.2 ± 55.1 pg/mL vs. 4.4 ± 26.5 pg/mL; p < 0.001). There was no significant difference in PlGF levels in the pre-eclamptic pregnant women in relation to gestational age or proteinuria levels (p > 0.05). The serum levels of VEGF, IL-17, IL-10 and TNF-α were lower in the pregnant women with PE when compared with their normotensive peers, while the IL-6 levels were higher; however, this difference was not statistically significant (p > 0.05). CONCLUSION: Serum PlGF levels were reduced in the pregnant women with PE and were unrelated to disease severity. Serum levels of VEGF, IL-17, IL-10 and TNF-α were reduced in the pre-eclamptic pregnant women when compared with their normotensive peers, without statistically significant differences.

TNF-R1 as a first trimester marker for prediction of pre-eclampsia.

OBJECTIVE: To examine whether the maternal serum concentration of the soluble receptor-1 of tumor necrosis factor-α (TNF-R1) at 11-13 + 6 weeks of gestation is a predictor of development of pre-eclampsia (PE). METHODS: This is a nested case-control study in which the concentration of TNF-R1 at 11 + 0 to 13 + 6 weeks was measured in 426 pregnant women in the first trimester. TNF-R1 values were expressed as multiples of the median (MoM) adjusted for maternal factors. The distributions of log TNF-R1 MoM in the control group and hypertensive disorders (early-PE [ePE], late-PE [lPE] and gestational hypertension [GH]) groups were compared. Logistic regression analysis was used to determine whether maternal factors, TNF-R1 or their combination make a significant contribution to the prediction of PE. Screening performance was determined by analysis of receiver-operating characteristics curves. RESULTS: Median concentration of TNF-R1 (ng/ml) was higher in ePE (2.62 ± 0.67), lPE (2.12 ± 0.56) and GH (2.19 ± 0.45) compared to controls (2.04 ± 0.42), p = 0.001. Logistic regression analysis demonstrated that the addition of TNFR-1 to maternal factors did not make a significant contribution to the prediction of PE. CONCLUSIONS: The maternal serum TNF-R1 concentration at 11-13 + 6 weeks of gestation was increased in pregnancies which developed hypertensive disorders, however, the addition of TNFR-1 did not improve the detection rate of these conditions compared with maternal factors alone.

Predicting small for gestational age in the first trimester of pregnancy using maternal ophthalmic artery Doppler indices.

OBJECTIVE: To assess the capacity of maternal ophthalmic Doppler indices for predicting small for gestational age (SGA) newborns in the first trimester of pregnancy. METHODS: We performed a prospective observational cohort study involving 499 singleton pregnancies during the first trimester scan (11-14 weeks). The following maternal ophthalmic Doppler indices were assessed: pulsatility index (PI), first diastolic peak velocity (PD1) and peak ratio (PR) = PD1/peak systolic velocity. We considered SGA all newborns with weight below 10th percentile. We used chi-square test (χ(2)) to compare the groups. We used area under receiver operating characteristics (ROC) curves with 95% confidence intervals (CI) and detection rate of 5% of false positive of each maternal ophthalmic Doppler index and the mean uterine artery PI for prediction SGA. RESULTS: 27 (5.4%) patients delivered SGA newborns, 12 (2.4%) patients developed preeclampsia (PE) and delivered SGA newborns, and 460 had uneventful pregnancies (controls). We observed significant difference of PI and PR between SGA (SGA and SGA+PE) and control groups, p = 0.043 and p = 0.014, respectively. To 5% of false positive, the detection rate of SGA (SGA and SGA+PE groups) using PI, PD1 and PR were 14.8, 3.7, 14.8, 16.7, 16.7 and 16.7%, respectively. Mean uterine PI was significantly higher in the SGA+PE group (p = 0.003). CONCLUSION: The isolated use of maternal ophthalmic Doppler indices or in combination with uterine artery Doppler, in the first trimester of pregnancy, was not efficient to predict SGA newborns.