Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

A closer look at discordant placental echogenicity: two cases under the microscope.

Discordant placental echogenicity is observed in MC pregnancies complicated with twin anemia-polycythemia sequence, but could also belong to complicated singleton gestation.

Incidence of Cerebral Injury in Monochorionic Twin Survivors after Spontaneous Single Demise: Long-Term Outcome of a Large Cohort.

OBJECTIVES: To evaluate incidence of cerebral injury and outcome in a large series of monochorionic (MC) twin survivors after spontaneous single fetal demise. METHODS: Retrospective analysis of all MC pregnancies with single fetal demise diagnosed at, or referred to, the Fetal Therapy Unit "U. Nicolini," V. Buzzi Children's Hospital, Milan, Italy, from 2004 to 2015. Survivors evaluation protocol included detailed ultrasound (US) of intracranial anatomy, Doppler investigation of peak systolic velocity in the middle cerebral artery (MCA-PSV), and magnetic resonance (MR). Data were collected on pregnancy characteristics, postnatal brain scan, and MR and neurological follow-up. RESULTS: Seventy-eight consecutive MC pregnancies were analyzed. Median gestational age (GA) at single fetal demise was 22 weeks (range 15-36); median interval between single demise and live birth was 105 days (range 1-175), with a median GA at birth of 36 weeks (range 23-41). Prenatal MR was performed in 57 of 78 cases (73%). Cerebral injury affected 14/78 (18%) co-twins, 2 of whom were born immediately after single demise, with postnatal diagnosis of cerebral injury; of the other 12 fetuses that were studied before birth, 10 had a prenatal diagnosis of lesion both with US and MR, one only with MR, and in one case, a grade III intraventricular hemorrhage was reported only after delivery, which occurred at 25 weeks, 5 weeks after the single demise. Signs of fetal anemia (MCA-PSV value above 1.55 MoM) were related to a higher risk of prenatal cerebral injury; cases with postnatal diagnosis of lesion were delivered at lower GA. CONCLUSIONS: Cerebral injury affects 18% of co-twin survivors after single fetal demise in MC twin pregnancies, and evaluation and follow-up of these cases can improve detection rate of such damage.

Longitudinal Doppler references for monochorionic twins and comparison with singletons.

OBJECTIVES: To construct monochorionic (MC) twin-specific longitudinal Doppler references for umbilical artery pulsatility index (UA-PI), middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and ductus venosus (DV) PI derived from a strictly selected cohort of uncomplicated MC twins. The secondary aim of the study was to compare our findings with singleton reference charts. METHODS: A retrospective evaluation was made of all consecutive uncomplicated MC twin pregnancies referred to our Unit from 2010 to 2018. Fortnightly serial examinations were performed of UA-PI, MCA-PI, MCA-PSV and DV-PI, according with the clinical protocol, from 20 to 37 weeks of gestation. We included cases with at least four ultrasound examinations, delivery at our hospital and complete neonatal follow up. A two-step method was used to trace the estimated centile curves: estimation of the median was performed with appropriate fractional polynomials by a multilevel model and estimation of the external centiles through the residuals (quantile regression). The comparison with singletons was made by plotting the references derived from the present study on the referred charts commonly used for singletons. RESULTS: The study group comprised 150 uncomplicated MC twin pairs. Estimated centiles (3rd, 5th, 10th, 50th, 90th, 95th, 97th) of UA-PI, MCA-PI, MCA-PSV and DV-PI in function of the gestational age are presented. The comparison with singletons showed substantial differences, with higher UA-PI and lower MCA-PI and PSV median values in MC twins. Median DV PI values were similar to the values for singletons, while the upper centiles were higher in MC twins. CONCLUSIONS: This study sets out MC twin-specific longitudinal references for UA-PI, MCA-PI, MCA-PSV and DV-PI derived from the largest series of uncomplicated MC twin pregnancies presently available. The comparison with singleton reference values underscores the deviation from physiology that is intrinsic to these unique pregnancies and supports the need for MC twin-specific charts.

Major Discordant Structural Anomalies in Monochorionic Twins: Spectrum and Outcomes.

Monochorionic twins, resulting from a single fertilized egg giving rise to two separate embryos, are monozygotic and considered genetically identical. However, discordant phenotypes have been reported in monozygotic twins. We analyzed a retrospective cohort of 155 monochorionic pregnancies (312 twins) with major discordant structural anomalies coded by the ICD-10 system in order to describe the spectrum of anomalies, the management of the pregnancies, and the perinatal outcome. Treatment options included conservative management, selective feticide with bipolar cord coagulation, or complete termination. All survivors underwent at least 24 months of postnatal follow-up. Discordancy was complicated by twin-to-twin transfusion syndrome in eight pregnancies (5%) and by selective intrauterine growth restriction in 41 (26%). Major structural anomalies affected one system in 139 cases (90%) and multiple systems in 16 (10%). Median gestational age at diagnosis was 19.1 weeks (IQR 16.4-21.3). The most frequent single-system anomalies involved the nervous and circulatory systems. In total, 72 anomalous twins (46%) and 116 normal co-twins (74%) were delivered at a median gestational age of 34.6 weeks (IQR 31.0-36.3). Neonatal/infant death of the anomalous twin occurred in 22 cases (14%), with an overall survival rate of 32% (50/155). Surviving anomalous twins underwent major surgery in 22/50 cases (44%), four of whom (8%) now suffer from severe neurologic morbidity. This study shows that a wide spectrum of major discordant structural anomalies can be found in monochorionic pregnancies. The outcome for the anomalous twin is poor, while the survival rate for the normal co-twin was 71%, with a favorable overall prognosis.

Familial Precocious Fetal Abnormal Cortical Sulcation.

The development of the human cerebral cortex is a complex and precisely programmed process by which alterations may lead to morphological and functional neurological abnormalities. We report familial cases of prenatally diagnosed abnormal brain, characterized by aberrant symmetrical mesial oversulcation of the parietooccipital lobes, in fetuses affected by abnormal skeletal features. Fetal brain anomalies were characterized by prenatal magnetic resonance imaging at 21 weeks of gestation and histologically evaluated at 22 weeks. Histological examination added relevant information showing some focal cortical areas of micropoligyria and heterotopic extension of the cortical plate into the marginal zone beneath the cortical surface. Genetic analysis of the fetuses excluded FGFR3 mutations known to be related to skeletal dysplasia and aberrant symmetrical oversulcation in other brain areas (temporal lobes). Hence, the present report suggests the existence of a class of rare syndromes of skeleton and brain development abnormality unrelated to FGFR3 mutations or related to other not described FGFR3 gene defects. Using magnetic resonance imaging, histopathology and molecular characterization we provide an example of a translational study of a rare and unreported brain congenital malformation.

Color-dye injection of monochorionic placentas and correlation with pregnancy complications.

INTRODUCTION: Vascular anastomoses in monochorionic (MC) twin placenta can be easily identified with color-dye injection. The aim of this study is to analyze the relationship between different type of anastomoses and twin pregnancy complications. METHODS: From January 2011 to October 2014, MC placentas were analyzed with color-dye injection and five group of pregnancies were identified: those that were not complicated (NC), those complicated with selective intrauterine growth restriction (sIUGR), twin-twin transfusion syndrome (TTTS), or twin anemia-polycitemia sequence (TAPS) and those with amniotic fluid discordance (AFD) between twins. Cases of TTTS treated with endoscopic laser coagulation of placenta anastomoses or cases with in utero death of one twin were excluded. RESULTS: A total of 118 MC placentas were observed, 58 (49%) NC, 35 (30%) sIUGR, 10 (8%) TTTS, 13 (11%) AFD and 2 (2%) TAPS. The median number of anastomoses was 7 (range 1-15), 8 (2-18), 4 (2-11), 7 (2-13) and 1 (1-1), respectively. At least one artero-venous anastomoses was found in the placenta observed, while the prevalence of artero-arterial anastomoses was 95% for NC, 91% for sIUGR, 60% for TTTS, and 77% for AFD; no TAPS placenta had this type of anastomoses. The diameter of arteroarterial anastomoses was greater in the AFD group (3.3 mm), compared to the NC, sIUGR and TTTS groups (2.3, 2.5 and 1.4 respectively, p 0.04). DISCUSSION: In this large serie of MC placenta analyzed with color-dye injection, a specific distribution of anastomoses emerged for twins with amniotic fluid discordance, which points to a need for intensive surveillance.

Fetoscopic laser coagulation of the vascular equator versus selective coagulation for twin-to-twin transfusion syndrome: an open-label randomised controlled trial.

BACKGROUND: Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome are typically treated with fetoscopic laser coagulation. Postoperative complications can occur due to residual vascular anastomoses on the placenta. We aimed to assess the efficacy and safety of a novel surgery technique that uses laser coagulation of the entire vascular equator (Solomon technique). METHODS: We undertook an open-label, international, multicentre, randomised controlled trial at five European tertiary referral centres. Women with twin-to-twin transfusion syndrome were randomly assigned by online randomisation (1:1) with permuted blocks to the Solomon technique or standard laser coagulation. The primary outcome was a composite of incidence of twin anaemia polycythaemia sequence, recurrence of twin-to-twin transfusion syndrome, perinatal mortality, or severe neonatal morbidity. Analyses were by intention to treat, with results expressed as odds ratios (ORs) and 95% CIs. This trial is registered with the Dutch Trial Registry, number NTR1245. FINDINGS: Between March 11, 2008, and July 12, 2012, 274 women were randomly assigned to either the Solomon group (n=139) or the standard treatment group (n=135). The primary outcome occurred in 94 (34%) of 274 fetuses in the Solomon group versus 133 (49%) of 270 in the standard treatment group (OR 0·54; 95% CI 0·35-0·82). The Solomon technique was associated with a reduction in twin anaemia polycythaemia sequence (3% vs 16% for the standard treatment; OR 0·16, 95% CI 0·05-0·49) and recurrence of twin-to-twin transfusion syndrome (1% vs 7%; 0·21, 0·04-0·98). Perinatal mortality and severe neonatal morbidity did not differ significantly between the two groups. Outside of the common and well-known complications of twin-to-twin transfusion syndrome and its treatment, no serious adverse events occurred. INTERPRETATION: Fetoscopic laser coagulation of the entire vascular equator reduces postoperative fetal morbidity in severe twin-to-twin transfusion syndrome. We recommend that fetoscopic surgeons consider adopting this strategy for treatment of women with twin-to-twin transfusion syndrome. FUNDING: Netherlands Organization for the Health Research and Development (ZonMw 92003545).

Early diagnosis, follow-up, and prenatal treatment of a case of TRAP sequence occurring in a dichorionic triamniotic triplet pregnancy.

We are reporting a case of twin reversed arterial perfusion (TRAP) sequence occurring in a dichorionic triamniotic triplet pregnancy with successful percutaneous prenatal treatment and excellent neonatal outcome. TRAP sequence was diagnosed at 11 weeks in a spontaneous dichorionic-triamniotic triplet. Sonographic assessment showed persistent arterial flow and development of hydrops in the acardiac twin. Percutaneous cord interstitial laser coagulation was performed, and the co-twin subsequently developed growth restriction. The 9-month-old twins have a normal developmental course. This report confirms that fetal intervention is indicated in cases of TRAP sequence in which the acardiac twin presents a significant enlargement on follow-up sonographic examinations.

Fetal pleural effusion.

Fetal pleural effusion, a nonspecific accumulation of fluid in the pleural space, is an uncommon anomaly which can be associated with aneuploidy and a range of other structural malformations or genetic syndromes. Spontaneous resolution is not rare and confers a good prognosis. Perinatal outcome is better for those fetuses without hydrops than those presenting with hydrops. A detailed review of the literature indicates that, for fetuses with persistent effusions, in utero intervention (repeated thoracocentesis, intrauterine shunting and pleurodesis) may improve the chances of survival.

Pulmonary hypertension due to spontaneous premature ductal constriction in fetal life: association with right bundle branch block.

We describe a case of fetal pulmonary hypertension and tricuspid regurgitation due to non pharmacologically induced ductal constriction observed at 36 weeks' gestational age. The hypertension resolved spontaneously soon after birth, with no functional consequences. Right bundle branch block is the only permanent anomaly, still being seen on the electrocardiogram at the age of 34 months.