Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

BACKGROUND AND AIMS: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. APPROACH AND RESULTS: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. CONCLUSIONS: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Dynamics of liver stiffness measurement and clinical course of primary biliary cholangitis.

BACKGROUND & AIMS: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. METHODS: We conducted an international retrospective cohort study among PBC patients treated with ursodeoxycholic acid (UDCA) and followed by vibration-controlled transient elastography (VCTE) between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation (LT) or death, was quantified using the hazard ratio (HR) and its confidence interval (CI). RESULTS: A total of 6,362 LSMs were performed in 3,078 patients (2,007 on UDCA alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1,000 person-years). LSM progressed in 59% of patients (mean 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (p<0.001). For example, the adjusted HRs (95% CI) associated with a 20% annual variation in LSM were 2.13 (1.89 - 2.45) for the increase and 0.40 (0.33 - 0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or LT was considered. CONCLUSIONS: Tracking longitudinal changes in LSM using VCTE provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate endpoint in PBC clinical trials.

Hepatocellular carcinoma in pregnancy: A systematic review.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis or chronic hepatitis B virus infection. Ultrasound evaluation, CT scan, and MRI are used to detect HCC. α-fetoprotein (AFP) is a common marker used to detect HCC in the non-pregnant population, which notoriously increases in pregnant women in relation to gestational age. Treatment is driven by the extent of the disease and the severity of underlying liver disease. Pregnancy may represent an obstacle to diagnosis and appropriate treatment of HCC. The aim of this descriptive systematic review was to describe the clinical features and maternal and neonatal outcomes of HCC in pregnancy. MATERIAL AND METHODS: We performed a systematic review of the literature about HCC diagnosed in pregnancy and the postpartum period, with signs or symptoms arising in pregnancy. We included case reports and case series describing the clinical features of women diagnosed with HCC, fibrolamellar variant of HCC, and mixed HCC and cholangiocarcinoma during pregnancy or the postpartum period (with onset of symptoms during pregnancy), from inception to March 2023. The study protocol was registered with the PROSPERO database (Registration number: ID CRD42021275584). RESULTS: We identified 180 records. The articles included in this systematic review were 47 case reports and 5 case series, for a total of 63 pregnancies. The two most frequent predisposing conditions were hepatitis B virus infection (30/63; 47%) and liver cirrhosis (14/63; 22%). Ultrasound evaluation was the most used technique to detect HCC. AFP was higher than normal in 28/46 patients tested (61%). Surgical treatment was the most used therapy, both during pregnancy and after delivery. Twenty-six patients (26/63; 42%) died within 6 months of diagnosis. Survival >24 months was 9% (4/46) in symptomatic and 29% (5/17) in asymptomatic women. No patient with cirrhotic liver survived more than 12 months. Thirty-eight newborns were alive at 28 days of age (38/63; 61%). CONCLUSIONS: Hepatocellular carcinoma in pregnancy is associated with a high risk of maternal and neonatal mortality. Diagnosis in asymptomatic high-risk women or following abnormal maternal serum AFP screening is associated with better maternal outcomes.

Intrapartum pyrexia, cardiotocography traces and histologic chorioamnionitis: a case-control study.

OBJECTIVES: To compare characteristics of labor, cardiotocography traces, and maternal and neonatal outcomes, in a cohort of pregnancies at term complicated by maternal intrapartum pyrexia, with or without a histologic diagnosis of chorioamnionitis. METHODS: This is a retrospective case-control study including pregnancies at term with detection of maternal intrapartum pyrexia, delivered between January 2020 and June 2021. Cardiotocography traces were entirely evaluated, since admission till delivery, and classified according to the International Federation of Obstetrics and Gynecology (FIGO) guideline. Maternal and neonatal outcomes were also recorded as secondary outcomes. Placentas have been studied according to the Amniotic Fluid Infection Nosology Committee. RESULTS: Forty four patients met the inclusion criteria and were included in the study cohort. There was a significant association between the use of oxytocin augmentation in labor and the histologic diagnosis of chorioamnionitis. A significative recurrence of loss and/or absence of accelerations at the point of pyrexia was also documented in women with histological chorioamnionitis compared to the others. CONCLUSIONS: Chorioamnionitis appears to be associated with myometrial disfunction, as suggested by the increased use of oxytocin augmentation during active labor of women at term with intrapartum pyrexia and histologic diagnosis of chorioamnionitis.

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. METHODS: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. RESULTS: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. CONCLUSIONS: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

Small-for-gestational-age fetus diagnosed in the second trimester: Possible etiologies and short-term neonatal outcomes.

INTRODUCTION: The aim of our study was to investigate the causes of fetal growth <10th centile diagnosed <26 weeks' gestation in singleton pregnancies and compare pregnancy outcomes in relation to the identified etiology. MATERIAL AND METHODS: Historical cohort study conducted in two Italian hospitals which included all small-for-gestational-age fetuses diagnosed between 18+0 and 26+0 weeks over a 10-year period. Fetuses were divided into three groups depending on the prenatally suspected etiology: chromosomal abnormalities (Group 1), malformations (Group 2) and isolated (Group 3). These groups were compared regarding pregnancy outcomes. Fetuses in Group 3 were divided into small-for-gestational-age and fetal growth restriction following the Delphi Consensus criteria and the outcomes were further compared. Fisher's Exact or Mann-Whitney test were used for comparison of groups. RESULTS: In all, 435 fetuses were included. Of these, 20 cases (4.6%) were associated with chromosomal abnormalities (Group 1), 98 (22.5%) with fetal malformations (Group 2) and 317 (72.9%) were isolated (Group 3). A higher percentage of live births was reported for Group 3 (P < 0.001). Termination of pregnancy was more common in Group 1 (P < 0.001). No differences in gestational age at delivery, birthweight, intrauterine death or neonatal death were detected within groups. Growth-restricted fetuses had lower gestational age at delivery, birthweight and number of live births (P < 0.001), higher rates of termination of pregnancy, intrauterine death (P < 0.001) and neonatal death <10 days (P = 0.002) compared to small-for-gestational-age. In 17 cases a chromosomal abnormality, genetic syndrome or adverse neurological outcome was diagnosed after birth: six from Group 2 (11.3% of live births in this group) and 11 from Group 3 (4.3%). CONCLUSIONS: We report that fetal growth <10th percentile diagnosed before 26 weeks is not isolated before birth in 27% of cases. Malformations and chromosomal abnormalities are common etiologies; therefore, detailed anomaly scans and invasive testing should be offered. In addition, there is a residual risk of neonatal death and postnatal diagnosis of a genetic syndrome or neurodevelopmental impairment despite normal prenatal tests. These results expand the small amount of information on the outcome of cases with very early diagnosis of impaired fetal growth currently available and highlight the importance of detailed counseling with couples.

A strange case of pleuritic pain in the third trimester of pregnancy.

Pulmonary sequestration is an uncommon congenital malformation of the lung, generally diagnosed in childhood or adolescence, corresponding to dysplastic lung tissue not communicating with the rest of vascular or bronchial lung system but receiving an arterial blood supply from systemic arteries. Currently, surgical resection is usually indicated in order to prevent or treat related symptoms or complications, although controversy exists regarding its use in asymptomatic patients and adults. We present the case of a 32-year-old pregnant woman with acute chest pain and vomiting diagnosed with intralobar sequestration at 32+2 weeks of gestation and treated with pulmonary lobectomy after giving birth by cesarean section at 33+0 weeks of gestation.

Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis.

BACKGROUND & AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. METHODS: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. RESULTS: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79-0.87) and 0.92 (0.89-0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM. CONCLUSIONS: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered. LAY SUMMARY: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses gradually, so surrogate markers (markers that predict clinically relevant outcomes like the need for a transplant or death long before the event occurs) are often needed to expedite the drug development and approval process. Herein, we show that liver stiffness measurement is a strong predictor of clinical outcomes and could be a useful surrogate endpoint in PBC trials.

Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach.

BACKGROUND AND AIMS: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC. APPROACH AND RESULTS: We collected data from 167 consecutive treatment-naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. CONCLUSIONS: In a multicenter study of treatment-naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.

An update of diagnostic efficacy of ultrasound and magnetic resonance imaging in the diagnosis of clinically significant placenta accreta spectrum disorders.

PURPOSE OF REVIEW: Systematic screening and diagnosis of placenta accreta spectrum disorder (PAS) either by ultrasound or magnetic resonance imaging (MRI) would allow referral of high-risk women to specialized multidisciplinary teams. We aimed to report recent findings regarding the diagnostic accuracy of ultrasound and magnetic resonance imaging in the diagnosis of PAS. RECENT FINDINGS: Recent evidence from the literature shows that both ultrasound and MRI are good tests to identify PAS in high-risk populations. Ultrasound can also be used safely to guide management decisions, concentrating greater resources in patients with the higher risk of clinically significant PAS requiring complex peripartum management. Moreover, there are increasing data showing that routine contingent screening for PAS disorders based on the finding of a placenta implanted low in the uterine cavity and previous uterine surgery is effective in a public healthcare setting. A contingent screening strategy for PAS is feasible if placental location is routinely assessed during routine scans, and may even start from the first trimester of pregnancy. SUMMARY: Ultrasound is an effective tool to screen pregnancies at high risk of PAS. In such pregnancies, ultrasound and MRI are effective imaging modalities for guiding management.

Ultrasound and magnetic resonance imaging in the diagnosis of clinically significant placenta accreta spectrum disorders.

OBJECTIVES: We aimed to assess the performance of ultrasound (US) and magnetic resonance imaging (MRI) signs for antenatal detection of placenta accreta spectrum (PAS) disorders in women with placenta previa (placental edge ≤2 cm from the internal uterine orifice, ≥260/7 weeks' gestation) with and without a history of previous Caesarean section. METHODS: Single center prospective observational study. US suspicion of PAS was raised in the presence of obliteration of the hypoechoic space between uterus and placenta, interruption of the hyperechoic uterine-bladder interface and/or turbulent placental lacunae on color Doppler. All MRI studies were blindly evaluated by a single operator. PAS was defined as clinically significant when histopathological diagnosis was associated with at least one of: intrauterine balloon placement, compressive uterine sutures, peripartum hysterectomy, uterine or hypogastric artery ligature, uterine artery embolization. RESULTS: A total of 39 women were included: 7/39 had clinically significant PAS. There were 6/18 cases of PAS with anterior placenta: hypoechoic space interruption and placental lacunae were the most sensitive sonographic signs (83%), while abnormal hyperechoic interface was the most specific (83%). On MRI, focal myometrial interruption and T2 intraplacental dark bands showed the best sensitivity (83%), bladder tenting had the best specificity (100%). 1/21 women with posterior placenta had PAS. There was substantial agreement between US and MRI in patients with anterior placenta (κ=0.78). CONCLUSIONS: US and MRI agreement in antenatal diagnosis of clinically significant PAS was maximal in high-risk women. Placental lacunae on ultrasound scan and T2 intraplacental hypointense bands on MRI should trigger the suspicion of PAS.

Fetoscopic laser ablation therapy in monochorionic diamniotic twin pregnancies with twin-to-twin transfusion syndrome treated at a single centre over 10 years: a retrospective study.

OBJECTIVES: To review experience with fetoscopic laser ablation of placental anastomoses to treat monochorionic diamniotic (MCDA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) in a single centre over a ten-year period. METHODS: A retrospective study on 142 MCDA twin pregnancies complicates by TTTS treated with equatorial laser ablation of placental anastomoses (2008-2018). Solomon technique was also applied after 2013. Survival rates, neonatal outcome, intraoperative and post-laser complications were recorded, and prognostic factors analysed. RESULTS: A total of 133 cases were included in the final analysis; 41 patients were at stage II (30.8%), 73 were at stage III (62.9%), while only 12 (9%) at stage I and two patients (1.7%) at stage IV. Solomon technique was applied in 39 cases (29.3%). Survival of both twins was 51.1% (68/133), of a single twin 20.3% (27/133), and of at least one 71.5% (95/133), with an overall survival of 61.3% (163/266). TAPS and recurrent TTTS occurred in 8 (6%) and 15 (11.3%) patients. Survival of both fetuses increased over time (44.6 vs. 57.3%). A posterior placenta (p<0.003) and the use of the Solomon technique (p<0.02) were more frequent in cases with survival of both fetuses, while TTTS recurrence was significantly associated to the loss of one or two fetuses (p<0.01). Such associations were confirmed at logistic regression analysis. CONCLUSIONS: Survival of both twins can improve over time and seems to be favourably associated with a placenta in the posterior location and the use of the Solomon technique.

Ductus venosus Doppler waveform pattern in fetuses with early growth restriction.

INTRODUCTION: We aimed to assess if maximum velocities of the ductus venosus flow velocity waveform are associated with adverse outcomes in early-onset fetal growth restriction. MATERIAL AND METHODS: Retrospective cohort study from two tertiary referral units, including singleton fetuses with estimated birthweight or fetal abdominal circumference ≤10th centile and absent or reversed end-diastolic velocity in the umbilical artery delivered between 26+0 and 34+0  weeks of gestation. Pulsatility index for veins, and maximum velocities of S-, D-, v- and a-waves, were measured in the ductus venosus within 24 hours of birth. Logistic regression was used to describe the relation between severe neonatal morbidity or neonatal death and clinical independent predictors. RESULTS: The study population included 132 early-onset fetal growth restriction fetuses. Newborns with neonatal morbidity or neonatal death had significantly lower values of v/D maximum velocity ratio multiples of the median (0.86 vs 095; P = 0.006) within 24 hours of birth. The v/D ratio remained a significant predictor of neonatal death or severe neonatal morbidity after adjusting for gestational age and birthweight (adjusted odds ratio 0.065, 95% confidence interval 0.004-0.957). CONCLUSIONS: Assessment of ductus venosus v/D maximum velocity ratio might help to identify fetal growth restriction fetuses at increased risk for neonatal death or severe neonatal morbidity. Confirmation in prospective studies is necessary.

The use of ultrasound-indicated cerclage or cervical pessary in asymptomatic twin pregnancies with a short cervix at midgestation.

INTRODUCTION: Spontaneous preterm birth in women with a twin pregnancy is one of the main causes of perinatal mortality and morbidity. Our aim was to review the perinatal outcome of asymptomatic twin pregnancies with a sonographic short cervical length during the second trimester treated with an ultrasound-indicated cerclage or cervical pessary. MATERIAL AND METHODS: Retrospective study on asymptomatic twin pregnancies with a short cervix (≤ 25 mm) at transvaginal ultrasound examination during the second trimester treated with a cervical cerclage or pessary (2001-2017). The rate of preterm birth < 28, 32 and 34 weeks of gestation, neonatal mortality, neonatal morbidity and composite adverse neonatal outcome were compared in the groups of women treated with cerclage or pessary. RESULTS: Seventy-four twin pregnancies underwent a cerclage while a cervical pessary was inserted in 34 women with twins at our Department: 36 women with an ultrasound-indicated cerclage and 20 with a pessary were included in the analysis. Median gestational age at delivery was higher in women treated with cerclage compared with those with pessary placement (P = .02) and the rate of preterm birth before 34 weeks of gestation was lower in the cerclage group (P = .03). Admissions to the Neonatal Intensive Care Unit were more frequent in pregnancies with pessary (P = .01), the length of admission was longer (P = .005) and composite adverse neonatal outcome occurred more often (P = .03) compared with the cerclage group. CONCLUSIONS: Ultrasound-indicated cerclage appears to reduce the rate of preterm birth before 34 weeks of gestation in asymptomatic twin pregnancies with a short cervix during the second trimester, and also the composite adverse neonatal outcome compared with pessary.

Brain-injured Survivors of Monochorionic Twin Pregnancies Complicated by Single Intrauterine Death: MR Findings in a Multicenter Study.

Purpose To describe and classify the range of brain injuries present at prenatal, in-utero magnetic resonance (MR) imaging in co-twin survivors of monochorionic (MC) twin pregnancies complicated by single intrauterine death (SIUD). Materials and Methods This retrospective, observational study from six tertiary fetal medicine centers that perform tertiary-level prenatal in-utero MR studies reviewed cases in which prenatal in-utero MR imaging had shown a brain injury in a surviving co-twin of a twin pregnancy with a MC component complicated by SIUD. Results Forty-two surviving MC twins were described. The primary distinction of brain abnormalities was into nonfocal and focal lesions. The nonfocal lesions included periventricular leukomalacia (group 1; two fetuses), generalized encephalomalacia (group 2; nine fetuses), posterior encephalomalacia (group 3; seven fetuses), and bilateral parasagittal and perisylvian injury (group 4; three fetuses). The focal lesions included nonhemorrhagic lesions (group 5; 14 fetuses) and hemorrhagic lesions (group 6; seven fetuses). Focal brain lesions were more likely to be found in the surviving MC pregnancies complicated by twin-twin transfusion syndrome (TTTS) (odds ratio, 2.4; 95% confidence interval: 1.3, 18.5; P = .01) and in fetuses that underwent an obstetric intervention (odds ratio, 2.8; 95% confidence interval: 1.8, 23.6; P = .006). Conclusion Brain injury of the surviving co-twin after SIUD in MC pregnancies is usually of ischemic origin and spares the brainstem and cerebellum. Focal brain lesions are more frequent in pregnancies complicated by TTTS or in those where an intervention has been performed.

Longitudinal reference ranges for serial measurements of myocardial performance index (MPI) by conventional and pulsed-wave tissue Doppler in monochorionic diamniotic twins at 17 to 26 weeks of gestation.

OBJECTIVE: To describe the longitudinal changes of fetal myocardial performance index (MPI) measured by conventional Doppler (MPI) and by pulsed-wave tissue Doppler (MPI') based on a prospective cohort of uncomplicated monochorionic diamniotic twin. METHOD: Single-center observational study. We measured MPI and MPI' in the right and left ventricles 3 times between 17 and 26 weeks of gestation. Second-degree fractional polynomials were built to obtain the best fitting curves in relation to gestational age (weeks) for each parameter. Gestational age-specific reference values were estimated by using two-level hierarchical models. RESULTS: Eighty-three uncomplicated monochorionic pregnancies were included in our study with a total of 249 observations. Fetal cardiac function was measured as MPI RV and LV, MPI' RV and LV at a mean gestational age of 18+3 (range 17+1 to 19+2 ), 22+3 (21+1 to 23+5 ), and 24+3 (22+6 to 26+2 ) weeks. The reference ranges for MPI LV, MPI RV, MPI' LV, and MPI' RV at 17 to 26 weeks were constructed and conditional percentiles calculated. CONCLUSION: The present study provides additional data on fetal cardiac function in uncomplicated monochorionic diamniotic twin gestations, describing the evolution of MPI and MPI' in both ventricles in uncomplicated monochorionic diamniotic pregnancies.

TRAP Sequence in Monochorionic/Monoamniotic (MC/MA) Discordant Twins: Two Cases Treated with Fetoscopic Laser Surgery.

INTRODUCTION: Ablation of the acardiac twin umbilical cord in the TRAP protects the normal donor twin. MATERIALS AND METHODS: Two case descriptions, one of interstitial laser photocoagulation and one of laser umbilical cord occlusion (L-UCO) of the acardiac twin in monochorionic monoamniotic pregnancies are reported. RESULTS: L-UCO in two pregnancies with TRAP syndrome in the second trimester resulted in intrauterine fetal death in both cases after 1 month. Case 1 had no detectable cause of fetal death. Case 2 had rupture of the amniotic sac causing anhydramnios and acute chorioamnionitis. A groove on the umbilical cord of the normal twin indicated a cord stricture due to cord entanglement. CONCLUSION: Our experience confirms that the best timing and optimal treatment of MC/MA twins complicated by TRAP sequence still remains a controversial clinical issue. Cord entanglement may continue be a potential clinical risk factor for adverse perinatal outcome even after ablation therapy.

Development of customized fetal growth charts in twins.

BACKGROUND: Twin gestations are at significantly higher risk of fetal growth restriction in comparison with singletons. Using fetal biometric charts customized for obstetrical and parental characteristics may facilitate an accurate assessment of fetal growth. OBJECTIVE: The objective of the study was to construct reference charts for the gestation of fetal biometric parameters stratified by chorionicity and customized for obstetrical and parental characteristics. STUDY DESIGN: Fetal biometric measurements obtained from serial ultrasound examinations in uncomplicated twin pregnancies delivering after 36 weeks of gestation were collected by 19 Italian fetal medicine units under the auspices of the Società Italiana di Ecografia Ostetrica e Ginecologica. The measurements acquired in each fetus at each examination included biparietal diameter, head circumference, abdominal circumference, and femur length. Multilevel linear regression models were used to adjust for the serial ultrasonographic measurements obtained and the clustering of each fetus in twin pregnancy. The impact of maternal and paternal characteristics (height, weight, ethnicity), parity, fetal sex, and mode of conception was also considered. Models for each parameter were stratified by fetal chorionicity and compared with our previously constructed growth curves for singletons. RESULTS: The data set included 1781 twin pregnancies (dichorionic, n = 1289; monochorionic diamniotic, n = 492) with 8923 ultrasonographic examinations with a median of 5 (range, 2-8) observations per pregnancy in dichorionic and 6 in (range, 2-11) monochorionic pregnancies. Growth curves of twin pregnancies differed from those of singletons, and differences were more marked in monochorionic twins and during the third trimester. A significant influence of parental characteristics was found. CONCLUSION: Curves of fetal biometric measurements in twins are influenced by parental characteristics. There is a reduction in the growth rate during the third trimester. The reference limits for gestation constructed in this study may provide a useful tool for a more accurate assessment of fetal growth in twin pregnancies.

The natural history of monoamniotic twin pregnancies: a case series and systematic review of the literature.

OBJECTIVE: To describe the natural history of monoamniotic twin pregnancies in contemporary practice. METHOD: Cohort study of monochorionic monoamniotic twin pregnancies with two live fetuses diagnosed at less than 16 weeks and prospectively followed up between 2004 and 2013. A systematic review of the literature using Medline, Embase and Scopus to determine the perinatal mortality rate after 24 weeks of gestation in monoamniotic twins was also performed. RESULTS: Twenty pregnancies were analyzed. Four were terminated (in three cases as a result of fetal abnormalities). Another six miscarried spontaneously. Among ten pregnancies reaching viability, there was double intrauterine death in one, and both fetuses were alive at delivery in the other nine. There were no neonatal deaths. Overall survival for fetuses alive at the initial scan was 18/40 (45%; 95% CI 29 to 62%). At meta-analysis of 13 studies (including the current series), the perinatal mortality rate after 24 weeks was 4.5% (95% CI 3.3 to 5.8%). CONCLUSIONS: Despite early diagnosis and intensive monitoring, of those fetuses alive before 16 weeks less than half survive until the neonatal period. Most losses are attributable to fetal abnormalities and spontaneous miscarriage and are therefore unlikely to be reduced by further improvements in fetal assessment and monitoring. © 2014 John Wiley & Sons, Ltd.

Outcome of monochorionic diamniotic twin pregnancies followed at a single center.

OBJECTIVE: We aim to evaluate the outcome of a cohort of monochorionic diamniotic twin pregnancies followed from the first trimester onwards at a single center. METHOD: This was a retrospective analysis of prospectively collected data from a series of 300 monochorionic diamniotic twin pregnancies referred to our twin clinic between 2001 and 2012. Pregnancies were followed from the first trimester and fortnightly after 16 weeks of gestation. Data on pregnancy and neonatal outcome were analyzed. RESULTS: There were two surviving infants in 259/300 (86.4%) pregnancies, one survivor in 22/300 (7.3%) and no survivors in 19/300 (6.3%) with an overall mortality of 60/600 (10%). Twin-twin transfusion syndrome was diagnosed in 33 cases (11%), isolated intertwin weight discordance ≥ 25% in 35 (11.6%) and major congenital structural anomalies in ten (3.3%). After 32 weeks, the prospective risk of spontaneous fetal intrauterine death was one in 248 (0.4%) per pregnancy. CONCLUSIONS: Despite specific prenatal fetal monitoring and management, monochorionic diamniotic twin pregnancies have still to be considered at high risk of mortality, although the prospective risk of intrauterine death after 32 weeks is low. Twin-twin transfusion syndrome and congenital anomalies were the main risk factors for mortality.