Preeclampsia is caused by placental impairment with increased expression of sFlt-1 (soluble fms-like tyrosine kinase 1) and decreased PlGF (placental growth factor); it has been associated with cardiovascular morbidity and mortality later in life, but the underlying mechanism remains unknown. The aim of this study was to determine whether sFlt-1 and PlGF levels during preeclampsia are associated to long-term cardiovascular risk. We prospectively recruited 43 women with previous preeclampsia and 21 controls with uncomplicated pregnancies. Cardiovascular risk assessment ≈12 years later included maternal hemodynamic, cardiac function and structure, biomarker analysis, and carotid-intima thickness evaluation. Women with previous preeclampsia had higher prevalence of hypertensive disorders and dyslipidemia than controls. In addition, they had worse global longitudinal strain, thicker left ventricular septal and posterior walls, more myocardial mass and increased carotid intima-media thickness compared with controls. PlGF during pregnancy correlated positively with high-density lipoprotein ( r =0.341; P =0.006), and negatively with global longitudinal strain ( r =−0.581; P <0.001), carotid intima-media thickness ( r =−0.251; P =0.045), and mean arterial blood pressure ( r =−0.252; P =0.045), when adjusted by study group. sFlt correlated negatively with high-density lipoprotein ( r =−0.372; P =0.002) and apolipoprotein A-1 ( r =−0.257; P =0.040), and positively with carotid intima-media thickness ( r =0.269; P =0.032) and left ventricular posterior wall thickness ( r =0.368; P =0.003). The antiangiogenic state present in preeclampsia is related to greater prevalence of cardiovascular risk factors ≈12 years after delivery. The knowledge of altered angiogenic factors may help detect women with a higher risk for premature cardiovascular disease, who will require earlier follow-up after delivery.

BackgroundIt is estimated that globally, approximately 13 million preterm infants are born annually and a much higher number of pregnancies are characterized by threatening preterm birth.FindingsA proportional inverse correlation between gestational age at delivery and neonatal mortality has been observed which is more prevalent in countries without high standard neonatal care. The socioeconomic burden of preterm birth is enormous, as preterm neonates are particularly prone to severe morbidity that may expand up to adulthood. Several strategies have been proposed for the prevention of preterm birth which can be sub-stratified as primary (when these apply to the general population), secondary (when they target women at risk), and tertiary (optimizing neonatal outcomes when preterm birth cannot any longer be prevented). The aim of this review is to summarize the most important strategies.

Background Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Methods Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). Discussion The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children’s neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. Trial registration NCT02996630 , on 4th December 2016 (retrospectively registered).

BACKGROUND: To date, no intervention has proved effective in reducing the spontaneous preterm birth rate in singleton pregnancies following an episode of threatened preterm labor and short cervix remaining. OBJECTIVE: This study was designed to ascertain whether cervical pessaries could be useful in preventing spontaneous preterm birth in women with singleton pregnancies and a short cervix after a threatened preterm labor episode. STUDY DESIGN: This open randomized controlled trial was conducted in 357 pregnant women (between 24(0)-33(6) weeks) who had not delivered 48 hours after a threatened preterm labor episode and had a short cervix remaining (<= 25 mm at 24(0)-29(6) weeks; <= 15 mm at 30(0)-33(6) weeks). Patients were randomly assigned to cervical pessary (179) or routine management (178). The primary outcome was the spontaneous preterm birth rate <34 weeks. Spontaneous preterm birth <28 and 37 weeks and neonatal morbidity and mortality were also evaluated in an intention-to-treat analysis. RESULTS: No significant differences between the pessary and routine management groups were observed in the spontaneous preterm birth rate <34 weeks (19/177 [10.7%] in the pessary group vs 24/175 [13.7%] in the control group; relative risk, 0.78; 95% confidence interval, 0.45-1.38). Spontaneous preterm birth <37 weeks occurred less frequently in the pessary group (26/175 [14.7%] vs 44/175 [25.1%]; relative risk, 0.58; 95% confidence interval, 0.38-0.90; P = .01). Pre-term premature rupture of membranes rate was significantly lower in pessary carriers (4/177 [2.3%] vs 14/175 [8.0%]; relative risk, 0.28; 95% confidence interval, 0.09-0.84; P = .01). The pessary group less frequently required readmission for new threatened preterm labor episodes (8/177 [4.5%] vs 35/175 [20.0%]; relative risk, 0.23; 95% confidence interval, 0.11-0.47; P<.0001). No serious adverse maternal events occurred; neonatal morbidity and mortality were similar in both groups. CONCLUSION: Pessary use did not significantly lower the spontaneous preterm birth rate <34 weeks in women with a short cervix remaining after a threatened preterm labor episode but did significantly reduce the spontaneous preterm birth rate <37 weeks, threatened preterm labor recurrence, and the preterm premature rupture of membranes rate.

Objectives: To determine intraobserver and interobserver variability in the measurement of different cervical length (CL) components at the first trimester (endocervical canal and isthmus), describe the optimum measurement method (single line or two lines) and establish a normality curve of first trimester CL in our population. Methods: Women who attended the first-trimester US scan, between 11.0 and 13.6?weeks of gestation at Vall d?Hebron Universitary Hospital, Barcelona, Spain were included. Inclusion criteria were singleton pregnancies in women over 18?years of age, no gestational complications, uterine malformations or uterine surgery. Lengths of the endocervical canal and uterine isthmus were measured using two methods. Results: Both methods for endocervical canal measurement, single line and two lines, showed low intraobserver variability between examiners, with no statistical differences in the majority of measurements. A correct correlation existed between examiners using the single-line two-line measurements, with a concordance correlation coefficient of 0.76. Conclusions: Cervical length in the first trimester was reproducible for the same physician and between different physicians; however, it is essential to ensure examiners receive adequate training in the technique.

Objectives: The aim of this study was to evaluate the relationships between brain injury biomarkers in intrauterine growth-restricted (IUGR) infants (S100B and neuron-specific enolase (NSE)) and neurodevelopment at 2 years of age. Methods: This prospective case-control study was a cooperative effort among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler variables were measured for each infant. Maternal venous blood and fetal umbilical arterial blood samples were collected at the time of delivery and neural injury markers S100B and NSE concentrations were measured. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). Results: Fifty six pregnancies were included. Thirty-one infants were classified as IUGR and 25 as non-IUGR. Neurodevelopmental evaluation at 2 years of age indicated that there were no between-group differences for any of the tests. For all patients in both groups, we found statistically significant inverse relationships between the concentrations of NSE in the cord blood and the results of the cognitive test (r = -271, p = .042), fine motor subtest (r = -280, p = .036), and social-emotional test (r = -349, p = .015). We also found statistically significant differences between the concentrations of S100B in the cord blood and the results of the cognitive test (r = -306, p = .022) and expressive communication subtest (r = -304, p = .023). For the IUGR group, we found a significant inverse relationship between the concentrations of S100B in the maternal serum and the results of adaptive behavior test (p < .05). In the non-IUGR group, we found statistically significant inverse relationships between the concentration of NSE in the cord blood and the results of the fine motor subtest (r = -446, p = .025) and social-emotional test (r = -489, p = .021). The difference between the concentration of S100B in the cord blood and the language composite score was also statistically significant (p = .038). Conclusions: At 2 years of age, the concentrations of NSE and S100B were higher in the non-IUGR and IUGR groups with the worst scores for some areas of neurodevelopmental evaluation. The value of these biomarkers for prognostic neurodevelopmental use requires further investigation for both non-IUGR and IUGR infants.

Objective To assess potential differences in the expression of antiangiogenic and angiogenic factors and of genes associated with chronic hypoxia in cerebral tissue of euploid fetuses with congenital heart disease (CHD) vs those without. Methods Cerebral tissue was obtained from 15 fetuses with CHD and 12 control fetuses that had undergone termination of pregnancy. Expression profiles of the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF), and of genes associated with chronic hypoxia were determined by real-time polymerase chain reaction in tissue from the frontal cortex and the basal ganglia of the fetuses. Results Expression of sFlt-1 was 48% higher in the frontal cortex (P = 0.0431) and 72% higher in the basal ganglia (P = 0.0369) of CHD fetuses compared with controls. The expression of VEGF-A was 60% higher (P = 0.0432) and that of hypoxia-inducible factor 2-alpha was 98% higher (P = 0.0456) in the basal ganglia of CHD fetuses compared with controls. No significant differences were observed between the two groups in the expression of PlGF and hypoxia-inducible factor 1-alpha. Conclusion An overall dysregulation of angiogenesis with a net balance towards an antiangiogenic environment was observed in the cerebral tissue of fetuses with CHD, suggesting that these fetuses may have an intrinsic angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life. Copyright (C) 2017 ISUOG. Published by John Wiley & Sons Ltd.

These guidelines are based upon most recent and updated evidence and they are adapted to a European perspective by an expert view of the problem. These guidelines are not intended to be a meta-anal...

Transition from design to adoption of innovations must be evidence-based and inform product development, regulatory approval and adoption

Objectives: To observe the modifications in cervical length (CL) in patients with and without cervical pessary (Arabin (R) ASQ 65/25/32) and correlate these modifications with gestational age at delivery.Study design: Prospective study of asymptomatic singleton pregnancies (PECEP-Trial) between weeks 20 + 0 and 23 + 6 with maternal short cervix (<25 mm) randomised into two groups: expectant management and cervical pessary.Results: This study included 380 pregnant women: 190 with pessary and 190 without pessary. Mean CL in both groups at the time of randomisation showed no statistically-significant differences (pessary group: 19.0 mm and management group: 19.0 mm; p = 0.9). Mean CL measured after randomisation was 15.4 mm in patients of the expectant management group and 21.5 mm in the pessary group. These differences were statistically significant (p < 0.0001). When means at randomisation and at the second measurement were compared, CL had decreased by 3.6 mm in the expectant management group and increased by 2.6 mm in the pessary group; this difference was statistically significant (p < 0.0001). Coefficients of correlation showed that among patients of both groups with the same CL at 20 weeks of gestation, those with a pessary gave birth later.Conclusions: Insertion of an Arabin cervical pessary increased CL in asymptomatic patients with a short cervix, which correlated with shorter gestational age at delivery. The cervical pessary halted the progressive decrease in CL, which correlated with longer gestational age at delivery.

BACKGROUNDThe aims of this study were to (i) compare the concentrations of two neural injury markers, S100B protein and neuron-specific enolase (NSE), in intrauterine growth-restricted (IUGR) fetuses and in fetuses with appropriate growth-for-gestational-age (AGA), and (ii) investigate potential relationships between concentrations of these markers, Doppler abnormalities, and adverse perinatal or neonatal outcomes.METHODSThis was a case-controlled, cooperative, prospective study among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler were measured. At the time of delivery, maternal venous blood and fetal umbilical arterial blood samples were collected. S100B and NSE concentrations were determined from these samples.RESULTSIn total, 254 pregnancies were included. Among these, 147 were classified as IUGR and 107 as AGA. There were no differences between the groups in S100B concentrations. However, levels of NSE in maternal and umbilical cord serum differed significantly between these groups (2.31 in AGA vs. 2.51 in IUGR in (P<0.05); and 2.89 in AGA vs. 3.25 in IUGR (P<0.05), respectively). No differences were observed in these neurological markers when stratified by perinatal or neonatal complications.CONCLUSIONAlthough some variations exist in these neurological markers, they did not correlate with perinatal or neonatal complications.

Objectives To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population.Methods This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor <37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications.Results In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early-onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index >90th percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)).Conclusions Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright (C) 2016 ISUOG. Published by John Wiley & Sons Ltd.

Hintergrund: Frühgeburten sind für mehr als 70% aller Todesfälle unter Neugeborenen und Säuglingen verantwortlich. Obwohl es sich nur bei 1,5% aller Schwangerschaften um Zwillingsschwangerschaften handelt, machen diese etwa 25% aller Frühgeburten aus. Nicolaides et al. haben nun im Rahmen einer Studie die Hypothese überprüft, dass die Anwendung eines Zervix-Pessars bei Zwillingsschwangerschaften die Frühgeburtenraten zu senken vermag.

Non-immune neonates and non-immune pregnant women are at risk of developing rubella, measles and mumps infections, including congenital rubella syndrome. We describe the seroepidemiology of measles, mumps and rubella (MMR) in neonates and pregnant women in Catalonia (Spain). Anti-rubella, anti-measles and anti-mumps serum IgG titres were assessed using enzyme-linked immunosorbent assay (ELISA) tests in 353 cord blood samples from neonates of a representative sample of pregnant women obtained in 2013. The prevalence of protective antibody titres in neonates was 96 % for rubella IgG (≥8 IU/ml), 90 % for measles IgG (>300 IU/ml) and 84 % for mumps IgG (>460 EU/ml). Slightly lower prevalences of protective IgG titres, as estimated from the cord blood titres, were found in pregnant women: 95 % for rubella IgG, 89 % for measles IgG and 81 % for mumps IgG. The anti-measles and anti-mumps IgG titres and the prevalences of protective IgG titres against measles and mumps increased significantly (p < 0.001) with maternal age. The prevalence of protective anti-measles IgG titres decreased by 7 % [odds ratio (OR) = 0.15, p < 0.001), the prevalence of protective anti-rubella IgG titres increased by 3 % (OR = 1.80, p < 0.05) and the MMR vaccination coverage (during childhood) in pregnant women increased by 54 % (OR = 2.09, p < 0.001) from 2003 to 2013. We recommend to develop an MMR prevention programme in women of childbearing age based on mass MMR vaccination or MMR screening and vaccination of susceptible women to increase immunity levels against MMR.

(Am J Obstet Gynecol. 2016;214(2):145–152) The primary risk factor for perinatal morbidity and mortality is noted to be spontaneous preterm birth (SPB) and the risk increases in twin gestations. Early and very early birth among twins is attributed to mothers having short cervical length (CL). It is also seen that 15% of women with twin gestations have CL≤25 mm. This measurement has become the benchmark for identifying women at risk of preterm delivery. Vaginal progesterone, cervical cerclage, and cervical pessary are the choices available for the management of patients with short CL. Use of vaginal progesterone did not reduce the rate of preterm delivery but the rate of neonatal morbidity decreased. Adverse outcome in twin gestations has been associated with cervical cerclage. Cervical pessary—a small ring shaped device made of silicone—was introduced in 1960 as a preventive measure for short CL. This device is inserted around the cervix, and a considerable fall in the preterm birth rate was recorded after this device came in use. Although, earlier clinical trial reports showed favorable results, the evidence came from nonrandomized study designs. Thus, further evidence supporting the role of cervical pessary in reducing the preterm birth rate was sought.

The integrity of the fetal amnion-chorion is an imperative for the preservation of a normal pregnancy in the human. The diagnosis of the status of the fetal membranes has traditionally been reduced to either intact or ruptured. In the last decades, evidence has accumulated demonstrating that this clinical approach may well be an over simplification. Practically, all maternal organs experienced physiologic or eventually pathologic changes during the length of the gestational period. We propose that the fetal membranes are also significantly impacted by those changes. The accurate, specific, simplified and low-cost diagnosis of the status of the fetal membranes is of critical importance for the assessment of risk to the pregnancy followed by efficient and prompt treatment. The presence of placental alpha macroglobulin-1 in the vagina specifically indicates a disruption in the integrity of the fetal membranes and may indirectly mean increased risk for preterm birth. Further research to properly characterize this marker and its importance in the care of pregnant woman at risk for preterm birth is strongly recommended.

Objectives: To evaluate the perinatal results of infants born between 23 and 25.6 weeks of gestation.Methods: Medical charts of all women giving birth prematurely (23-25.6 w) from January 2005 to December 2011 were retrospectively reviewed. Cases of malformed infants or deliveries elsewhere were excluded.Results: 198 infants were included. Chorioamnionitis occurred in 86 (43.4%) of the whole group: 26 (86.7%) in the 23-week; 35 (53.8%) in the 24-week and 25 (24.3%) in the 25-week groups. Foetal maturation with antenatal corticosteroids was complete in 119 cases (60.1%): 4 (13.3%) in the 23-week; 35 (53.8%) in the 24-week and 80 (77.7%) in the 25-week groups. Foetal death at birth occurred in 22 cases (11%) and 61 newborns (30.8%) died in the neonatal period. Of the 106 survivors with 2 years complete follow-up, 45 infants (42.4%) did not present sequelae; 16 infants (15.1%) had severe sequelae. A 66.6% (4) of infants born at 23 weeks of gestation did not present sequelae compared with a 32.3% (11) at 24 weeks and 45.4% (30) at 25 weeks.Conclusions: The chorioamnionitis rate was higher when gestational age was lower. The foetal maturation rate was higher when gestational age was higher. A low severe sequelae rate was observed in the whole series, particularly in the 23-week group where the rate was lower than expected; however, these results could have been influenced by the small size of the 23-week group.

Abstract Objectives: The objective of this study is to evaluate obstetric outcomes in women with heart disease and determine whether current multidisciplinary management approaches adversely affect the mother, the neonate, or both. Also to compare the accuracy of several risk scores (RS) including the modified World Health Organization classification (mWHO) and CARPREG to predict obstetric and neonatal complications and to study the addition value of Uteroplacental-Doppler flow (UDF) parameters to predict obstetric complications. Methods: A prospective cohort study examined outcomes in women with heart disease (HD), the majority of whom had corrective surgery and delivered between January 2007 and March 2012. Results: One hundred and seventy-four patients with 179 pregnancies were included in the study. Obstetric complications, including premature labor, arose in 87 patients (48.6%). Neonatal complications were observed in 11 cases (7%). On multivariate analysis, maternal heart disease was predictive of adverse perinatal events (46 cases, 25.7%) and mode of delivery (Thierry’s spatula) of third- or fourth-degree perineal tears (six cases, 3.2%). mWHO classification predicted obstetric complications (p = 0.0001) better than the CARPREG study. Impaired UDF (uterine artery pulsatility index-20 weeks and umbilical artery pulsatility index-32 weeks in HD versus healthy women: 20w 1.12 versus 1.34, p = 0.005; 32w 0.87 versus 1.09, p = 0.008) was associated with adverse obstetric and offspring outcome in the group of HD pregnant women. Conclusions: Nearly 50% of pregnancies were associated with an adverse obstetric outcome, particularly IUGR. mWHO was better at predicting obstetric and neonatal complications that CARPREG in all cathegories. Furthermore, compromised UDF combined with mWHO improved the prediction of obstetric and offspring complications in this population.