sFlt-1 Levels as a Predicting Tool in Placental Dysfunction Complications in Multiple Pregnancies.

BACKGROUND: several studies have demonstrated that angiogenic markers can improve the clinical management of hypertensive disorders (HDs) and fetal growth restriction (FGR) in singleton pregnancies, but few studies have evaluated the performance of these tests in multiple pregnancies. Our aim was to investigate the role of soluble fms-like tyrosine kinase 1 (sFlt-1) in predicting adverse obstetric outcomes in hospitalized multiple pregnancies with HD (preeclampsia/gestational hypertension/uncontrolled chronic hypertension) and/or FGR in one or more fetuses. METHODS: A retrospective analysis of multiple pregnancies with HD/FGR occurring after the 20th gestational week. Pregnant women were divided into two groups: women with high levels of sFlt-1 and those with low levels of sFlt-1. A value of sFlt-1 greater than or equal to 15,802 pg/mL was considered arbitrarily high, as it is equivalent to two times the 90th percentile expected in an uncomplicated full-term singleton pregnancy based on data from a prospective multicenter study (7901 pg/mL). RESULTS: The cohort included 39 multiple pregnancies. There were no cases of birth <34 weeks, HELLP syndrome, ICU admission, and urgent cesarean sections for HD/FGR complications reported among women with low levels of sFlt-1. CONCLUSIONS: A cut-off value of sFlt-1 ≥ 15,802 pg/mL could represent a valuable tool for predicting adverse obstetric outcomes in multiple pregnancies hospitalized for HD/FGR disorders, regardless of gestational age and chorionicity.

Delivery and feto-neonatal outcomes of diamniotic twin pregnancies in women with no chronic disease or gestational complications: impact of mode of conception.

Introduction: Autologous and heterologous assisted reproductive technology (ART) conceptions have been on the rise for the last few decades and alongside with that have the rate of multiple pregnancies. Multiple gestations are associated with high odds of gestational complications and, in turn, adverse delivery and feto-neonatal outcomes. Whether ART-conception further increases such elevated risk is still debated. ART is more commonly accessed by older women with chronic diseases, which relate to heightened likelihood of complications. We decided to investigate the influence of autologous and heterologous ART conception compared to spontaneous conception on delivery and feto-neonatal outcomes of diamniotic twin pregnancies in a cohort of healthy women with no chronic conditions or gestational complications.Materials and methods: Retrospective cohort study among diamniotic twin pregnancies in mothers without pregestational or gestational disease. Delivery and feto-neonatal outcomes were compared among three groups according to mode of conception: (1) spontaneous conception (SC, referent group, n = 251 pregnancies), (2) autologous ART-conception (A-ART, n = 87), and (3) heterologous ART-conception (H-ART, n = 22).Results: At adjusted analyses, twin pregnancies conceived by A-ART showed a twofold heightened risk of delivery by urgent/emergent cesarean section, as well as four and sevenfold increase in odds of blood loss >1000 and >1500 mL, respectively. H-ART pregnancies were at fivefold higher risk of undergoing prelabor cesarean section compared to SC, whereas no differences were identified for odds of severe post-partum hemorrhage. Also, A-ART and H-ART gestations displayed fetal and neonatal outcomes similar to SC pregnancies when analysis was adjusted for relevant confounding factors.Conclusion: Our results suggest that both A-ART and H-ART conception associate with increased odds of operative delivery among diamniotic twin pregnancies in healthy mothers with no chronic diseases or gestational complications. Also, a higher risk of severe postpartum hemorrhage appears to relate to A-ART independent of mode of delivery and maternal age. Further studies with larger series of uncomplicated twin pregnancies are warranted to improve our understanding of the relationship of ART to adverse delivery outcomes.

Neonatal hypoxia of the second twin after vaginal delivery of the first twin: what matters?

Objective: Optimal management of twin deliveries is controversial. We aimed to assess potential risk factors correlated to the development of hypoxia in the second twin after vaginal delivery of the first twin. Study design: This is a retrospective observational study including diamniotic twin pregnancies delivering at our Institution at 35 weeks of gestational age or more, weighing ≥1800 g. Hypoxia was defined as at least one of the following: Apgar score <5 at 10 minute, neonatal resuscitation for >10 minutes, neonatal acidosis (pH ≤7 and/or BE ≥12 mmol/L). Results: A number of 275 diamniotic twin pregnancies met the inclusion criteria and were divided within the following groups: (1) second twin not developing neonatal hypoxia (n = 265); and (2) second twin developing neonatal hypoxia (n = 10). The rate of second twins with neonatal hypoxia during the study period was 3.6% (10/275). Abnormal cardiotocography during the intertwin delivery interval, defined as ACOG category III, was significantly correlated to second twin hypoxia. Of interest, there was no significant difference in the intertwin delivery interval between the study groups. In addition, breech presentation of the second twin did not show to be a risk factor for neonatal hypoxia. None of the second twins developing neonatal hypoxia was reported to have encephalopathy (follow up of at least 24 months). At multivariate analysis, only abnormal cardiotocography was an independent risk factor for second twin hypoxia (OR 17.8, 95% CI 4.1-77.2). Conclusions: In our study, neonatal hypoxia was significantly correlated to abnormal cardiotocography, while intertwin delivery interval was not correlated to the development of this adverse neonatal outcome.

What is the effect of intertwin delivery interval on the outcome of the second twin delivered vaginally?

Objective: Optimal management of twin deliveries is controversial. We aimed to assess if intertwin delivery interval, after vaginal delivery of the first twin, may have an influence on adverse neonatal outcomes of the second twin Study design: This is a retrospective observational study including diamniotic twin pregnancies with vaginal delivery of the first twin, between January 2000 and July 2017. Inclusion criteria were diamniotic pregnancies and vaginal delivery of the first twin. We excluded higher twin order, monoamniotic pregnancies, cesarean delivery of the first twin and patients with missing data. Results: A number of 400 diamniotic twin pregnancies met the inclusion criteria and were divided, considering intertwin delivery interval into (1) ≤30 minutes (n = 365); and (2) >30 minutes (n = 35). Considering the two study groups, maternal and first twin characteristics and outcomes were similar. Second twin reported higher incidence of cesarean section and vacuum delivery, but similar incidence of neonatal adverse outcomes, in case of intertwin interval >30 minutes. At multivariate analysis, a difference between second and first twin weight ≥25% was correlated to neonatal adverse outcome, while we did not found this correlation with a cut-off of 30 minutes. Conclusions: In our study, growth discrepancy between twins was significantly correlated to adverse neonatal outcomes, while intertwin delivery time was not an influencing factor. So, in line with this result, in our clinical practice, we do not use a fixed time in which both twins should be delivered, neither in monochorionic nor in dichorionic pregnancies, when fetal wellbeing was demonstrated during labor.

2D versus 3D real time ultrasound with live xPlane imaging to visualize aortic and ductal arches: comparison between methods.

BACKGROUND: The diagnosis of congenital heart defects is challenging, especially for what concerns conotruncal anomalies. Indeed, although the screening techniques of fetal cardiac anomalies have greatly improved, the detection rate of conotruncal anomalies still remains low due to the fact that they are associated with a normal four-chamber view. Therefore, the study aimed to compare real-time three-dimensional echocardiography with live xPlane imaging with two-dimensional (2D) traditional imaging in visualizing ductal and aortic arches during routine echocardiography of the second trimester of gestation. METHODS: This was an observational prospective study including 114 women with uncomplicated, singleton pregnancies. All sonographic studies were performed by two different operators, of them 60 by a first level operator, while 54 by a second level operator. A subanalysis was run in order to evaluate the feasibility and the time needed for the two procedures according to fetal spine position and operator's experience. RESULTS: The measurements with 2D ultrasound were performed in all 114 echocardiographies, while live xPlane imaging was feasible in the 78% of the cases, and this was mainly due to fetal position. The time lapse needed to visualize aortic and ductal arches was significantly lower when using 2D ultrasound compared to live xPlane imaging (29.56 ± 28.5 s vs. 42.5 ± 38.1 s, P = 0.006 for aortic arch; 22.14 ± 17.8 s vs. 37.1 ± 33.8 s, P = 0.001 for ductal arch), also when performing a subanalysis according to operators' experience (P < 0.05 for all comparisons). Feasibility of live xPlane proved to be correlated with the position of the fetal spine and the operator's experience. DISCUSSION: To find a reproducible and standardized method to detect fetal heart defects may bring a great benefit for both patients and operators. In this scenario live xPlane imaging is a novel method to visualize ductal and aortic arches. We found that the position of the fetal spine may affect the feasibility of the method since, when the fetal back is anterior or transverse, the visualization of the correct view of three-vessels and trachea in order to set the reference line properly becomes more challenging. In addition, the fetal spine position influences the duration of the ultrasound examination. Regarding operator's skills and experience, in our study a first level operator was able to perform the complete 2D and xPlane examination in a lower number of cases compared to second level operators. In addition, the time required for the complete examination was higher for first level operators. This means that this technique is based on an adequate operators' expertise.

Influence of weight gain, according to Institute of Medicine 2009 recommendation, on spontaneous preterm delivery in twin pregnancies.

BACKGROUNDS: Maternal total weight gain during pregnancy influences adverse obstetric outcomes in singleton pregnancies. However, its impact in twin gestation is less understood. Our objective was to estimate the influence of total maternal weight gain on preterm delivery in twin pregnancies. METHODS: We conducted a retrospective cohort study including diamniotic twin pregnancies with spontaneous labor delivered at 28 + 0 weeks or later. We analyzed the influence of total weight gain according to Institute of Medicine (IOM) cut-offs on the development of preterm delivery (both less than 34 and 37 weeks). Outcome were compared between under and normal weight gain and between over and normal weight gain separately using Fisher's exact test with Holm-Bonferroni correction. RESULTS: One hundred seventy five women were included in the study and divided into three groups: under (52.0%), normal (41.7%) and overweight gain (6.3%). Normal weight gain was associated with a reduction in the rate of preterm delivery compared to under and over weight gain [less than 34 weeks: under vs. normal OR 4.97 (1.76-14.02), over vs. normal OR 4.53 (0.89-23.08); less than 37 weeks: OR 3.16 (1.66-6.04) and 6.51 (1.30-32.49), respectively]. CONCLUSIONS: Normal weight gain reduces spontaneous preterm delivery compared to over and underweight gain.

Selective IUGR in dichorionic twins: what can Doppler assessment and growth discordancy say about neonatal outcomes?

OBJECTIVE: The aim of the present study was to assess, in a population of dichorionic twin pregnancies with selective growth restriction, the effect of inter-twin differences by use of Doppler velocimetry and fetal growth discordancy on perinatal outcomes. METHODS: This was a retrospective study including dichorionic twin pregnancies from January 2008 to December 2015 at the Department of Obstetrics and Gynecology of Fondazione MBBM. Only dichorionic twin pregnancies affected by selective intrauterine growth restriction (IUGR) delivering at ≥24 weeks were included in the study. RESULTS: We found that twin pregnancies with inter-twin estimated fetal weight (EFW) discordance ≥15% were significantly associated with a higher risk of preterm delivery before 32 (P=0.004) and 34 weeks (P=0.04). Similarly, twin pregnancies with inter-twin abdominal circumference (AC) discordance ≥30° centiles were associated with a higher rate of neonatal intensive care unit (NICU) admission (P=0.02), neonatal resuscitation (P=0.02) and adverse neonatal composite outcome (P=0.04). Of interest, when comparing twin pregnancies according to Doppler study, growth restricted twins had a higher rate of composite neonatal outcome and in multivariate analysis, an abnormal Doppler was an independent risk factor for this outcome. CONCLUSIONS: Our study associated growth discrepancy with specific pregnancy outcomes, according to defined cut-offs. In addition, we demonstrated that an abnormal umbilical artery Doppler is independently associated with a composite neonatal adverse outcome in growth restricted fetuses.

Stillbirths in singletons, dichorionic and monochorionic twins: a comparison of risks and causes.

OBJECTIVES: To estimate the risk of stillbirth in dichorionic and monochorionic twins compared with singletons, and to evaluate the relevant causes of stillbirth in each group. STUDY DESIGN: A retrospective cohort analysis of all pregnancies ≥22 weeks of gestation was performed at a tertiary care center from January 1995 to June 2011. The overall fetal survival and the prospective risk of stillbirth were compared in monochorionic diamniotic (MCDA) twins, dichorionic diamniotic (DCDA) twins, and singletons. Causes of stillbirth were classified using the ReCoDe classification and were compared among the three study groups. RESULTS: A total of 46,200 singletons, 462 MCDA twins and 1108 DCDA twins were included in the study. Both Kaplan-Meier analysis and prospective risk calculation showed that MCDA twins had the highest risk of stillbirth (OR ranging between 13.5 95% CI 8.7-20.7 at 22.0-24.6 weeks and 4.0 95% CI 1.1-13.1 at 31.0-33.6 weeks, compared to singletons), while singletons had the lowest. Main causes of stillbirth were major congenital malformations in singletons (25.1%) and in DCDA twins (75%), and twin-twin transfusion syndrome in MCDA twins (81.5%). When excluding fetuses affected by major congenital anomalies, MCDA twins (p<0.001) but not DCDA twins (p=0.2) remained at increased risk for stillbirth compared with singletons. CONCLUSION: The risk of stillbirth is significantly higher both in MCDA and DCDA twins compared with singletons. Stillbirths are mainly due to twin-twin transfusion syndrome in MCDA twins and major congenital anomalies in DCDA twins. When major congenital anomalies are excluded, DCDA twins have a similar in utero mortality to singletons.

Perinatal complications in twin pregnancies after 34 weeks: effects of gestational age at delivery and chorionicity.

OBJECTIVE: To evaluate the perinatal outcome of twins approaching term in relation to chorionicity and gestational age at delivery. STUDY DESIGN: We accessed data pertaining to a cohort of 471 twin pregnancies with certain chorionicity delivered at > 34.0 weeks' gestation. Twin gestation per se, estimated fetal weight below the 10th percentile, or any intertwin discordance was not an indication for delivery before 40.0 weeks. Predictors of adverse perinatal outcome were identified using logistic regression analysis. RESULTS: There were no stillbirths. Adverse neonatal outcome occurred in 27% of monochorionic versus 16% of dichorionic gestations. At multivariate analysis, lower gestational age at delivery (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.57 to 0.87), monochorionicity (OR 2.06, 95% CI 1.16-3.63), and either twin being growth-restricted (OR 2.35, 95% CI 1.22 to 4.54) were independent predictors of adverse neonatal outcome. Analysis of adverse neonatal outcome stratified by gestational age and chorionicity identified 36 to 37 weeks as optimal timing for delivery of monochorionic twins, and dichorionic twin pregnancies should be allowed to continue until term. CONCLUSION: Among twin gestations delivered after 34 weeks with appropriate fetal growth, reassuring fetal status at weekly assessment, and absence of obstetric complications, delivery after 36 weeks for monochorionic twins and at term for dichorionic twins minimizes the risk of stillbirths and neonatal morbidity.

A multicenter, case-control study on risk factors for antepartum stillbirth.

OBJECTIVE: As the influence of socio-demographic variables, lifestyle and medical conditions on the epidemiology of stillbirth (SB) is modified by population features, we aimed at investigating the role played by these factors on the incidence of SB in a developed country. STUDY DESIGN: Multivariate logistic regression analysis (OR with 95% CI) was utilized in a prospective multicentre nested case-control study to compare in a 1:2 ratio stillborn of >22 weeks gestation with matched for gestational age live-born (LB) infants. Intrapartum SB were excluded. RESULTS: Two hundred fifty-four consecutive SBs and 497 LBs were enrolled. Socio-demographic variables were equally distributed. Fetal malformations (7.96, 2.69-23.55), severe intrauterine growth restriction (IUGR) (birthweight ≤ 5(th) %ile) (4.32, 2.27?8.24), BMI > 25 (2.87, 1.90-4.33), and preeclampsia (PE, 0.40, 0.21-0.77) were recognized as independent predictors for SB. At term, only BMI > 25 was associated with SB (7.70, 2.9-20.5). CONCLUSION: Fetal malformations, severe IUGR and maternal BMI > 25 were associated with a significant increase in the risk of SB; PE presented instead a protective role. Maternal BMI > 25 was the only risk factor for SB identified in term pregnancies.

Identifying the causes of stillbirth: a comparison of four classification systems.

OBJECTIVE: To identify the classification protocol for stillbirth that minimizes the rate of unexplained causes. STUDY DESIGN: All stillbirths at > 22 weeks from 1995-2007 underwent a workup inclusive of fetal ultrasonography, amniocentesis for karyotype and cultures, placental histology, fetal autopsy, skin biopsy, total body X-ray, maternal testing for thrombophilias, TORCH, Parvovirus spp, thyroid function, indirect Coombs, Kleiheuer-Betke test, and genital cultures. To such a cohort, we applied the 4 most commonly used classification protocols. RESULTS: The stillbirth rate during the study period was 0.4% (154/37,958). The RoDeCo classification provided the lowest rate of unexplained stillbirth (14.3%) compared with Wigglesworth (47.4%), de Galan-Roosen (18.2%), and Tulip (16.2%) classifications. Mean gestational age at stillbirth in unexplained vs explained stillbirth was similar in the 4 protocols. CONCLUSION: Adoption of a consistent and appropriate workup protocol can reduce the rate of unexplained stillbirth to 14%.