Sabrina Cozzolino

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%.

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 ≤5th %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.

Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death

OBJECTIVE To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95% CI: 1.3-13.5). CONCLUSION These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.

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.

Expectant management in di-chorionic pregnancies complicated by discordant anomalous twin

Abstract Fetal malformations are more frequent in twins than in singletons. The aim of our study was to define the influence of a malformed twin on di-chorionic pregnancy outcomes. We performed a retrospective cohort study of di-chorionic pregnancies delivered between 2000 and 2015. Exclusion criteria were: both twins affected by fetal malformations, double intra-uterine fetal death in pregnancies without fetal malformation, selective feticide and therapeutic pregnancy termination. We compared maternal and fetal outcomes of di-chorionic pregnancies not complicated by fetal malformations with pregnancies affected by a single malformed fetus with conservative management. We included 642 di-chorionic pregnancies: 56 (case group, 8.7%) with one twin affected by a malformation (20 minor, 36 major ones), 586 (control group, 91.3%) without fetal malformation. No differences were found on maternal and not malformed co-twin outcomes when compared to pregnancies with no malformation; case vs control group presented similar rates of preeclampsia (8.9% vs. 10.8%, respectively), intrauterine growth restriction (7.1% vs. 9.4%) and composite adverse neonatal outcomes (19.6% vs. 15.1%). No case of fetal death in not malformed co-twin was reported. Expectant management could be a safe option for both mother and co-twin in case of di-chorionic twin pregnancy complicated by only one malformed fetus.

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.

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

Abstract 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.

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

Abstract 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.

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

Abstract 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.