Long-Term Outcome of Monochorionic Twins after Fetoscopic Laser Therapy Compared to Matched Dichorionic Twins.

INTRODUCTION: The only causal therapy is fetoscopic laser surgery (FLS). The aims of this study were to analyze the long-term outcome of monochorionic twins treated by FLS, including their school career, need for therapy and special aid equipment, and free-time activities, and compare their outcome to matched dichorionic twins. MATERIAL AND METHODS: Among the 57 women treated at a single fetal treatment center between 2008 and 2017 with FLS because of twin-to-twin transfusion syndrome, 25 women with 42 children were included in the FLS group. The control group consisted of 16 dichorionic twin pairs matched for birth year, gestational age (GA), birth weight, and sex. The long-term outcome was assessed by a parental questionnaire and a standardized neurodevelopmental examination for children born before 32 gestational weeks or with a birth weight lower than 1500 g. They were also registered into the Swiss Neonatal Network database. The primary outcome was event-free survival, defined as normal neurology, behavior, vision, and hearing. The secondary outcomes were school career, need for therapy and special aid equipment, and free-time activities. RESULTS: An event-free survival was found in 32 children (76%) in the laser and in 24 children (75%) in the control group (p = 0.91). Neurological anomalies were found in 5 children (12%) in the laser group and 3 children (9%) in the control group (p = 1.00). Multiple logistic regression analysis showed that GA at delivery was the only predictive factor for event-free survival. There were no significant differences regarding school career, therapies, or special aid equipment between the 2 groups. We found that children without FLS were involved in more free-time activities and needed fewer breaks during physical activity than children with FLS during pregnancy. CONCLUSION: The outcome of monochorionic twins treated with FLS is comparable to the outcome of dichorionic twins. Long-term neurodevelopment in the cohort was mainly dependent on GA at birth.

Risk Factors for Preterm Birth following Open Fetal Myelomeningocele Repair: Results from a Prospective Cohort.

BACKGROUND: Fetal myelomeningocele (fMMC) repair is a therapeutic option in selected cases. This study aimed to identify risk factors for preterm birth (PTB) following open fMMC repair. METHODS: Sixty-seven women underwent fMMC repair and delivered a baby between 2010 and 2018 at our center. Demographic, surgical, and pregnancy complications, including potential risk factors for PTB such as preterm premature rupture of membranes (PPROM), chorioamniotic membrane separation (CMS), and placental abruption were evaluated. RESULTS: Maternal body mass index, maternal age, parity, previous uterine surgery, gestational age at fetal surgery, total surgery duration, surgical subcutaneous hematoma, oligohydramnios, and amniotic fluid leakage were not identified as risk factors for PTB. CMS (p = 0.028, 92 vs. 52%) and PPROM (p = 0.001, 95 vs. 52%) were highly associated with PTB. Placental abruption was found more often in women after fMMC repair than in a general obstetrical population (12 vs. 1%) and ended in premature birth in all cases (p = 0.024, 100 vs. 60%). However, the majority of women delivered at a gestational age >35 weeks. CONCLUSIONS: In our study cohort, risk factors for PTB were PPROM, CMS, and placental abruption, whereas surgery duration did not influence outcome. We conclude that the surgery technique should aim to minimize CMS and amniotic fluid leakage.

Benchmarking against the MOMS Trial: Zurich Results of Open Fetal Surgery for Spina Bifida.

INTRODUCTION: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results. MATERIALS AND METHODS: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared. RESULTS: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters. CONCLUSION: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care.

Outcome after fetoscopic laser coagulation in twin-twin transfusion syndrome - is the survival rate of at least one child at 6 months of age dependent on preoperative cervical length and preterm prelabour rupture of fetal membranes?

Purpose: Twin-to-twin transfusion syndrome (TTTS) complicates 10-15% of all monochorionic twin pregnancies. Selective laser coagulation of placental anastomoses is the only causal therapy. The aim of this study was to analyze the neonatal survival, the survival rate of at least one child at 6 months of age, and maternal outcome after laser therapy in a Swiss cohort.Material and methods: Between 2008 and 2014, 39 women were treated with fetoscopic laser procedure due to TTTS. Two women were excluded from the study because of missing informed consent or loss of follow-up. The women were divided into two groups: group 1 with a cervical length >25 mm and group 2 with a cervical length ≤25 mm. The primary end point was the survival rate of at least one child at 6 months of age and its dependence on maternal preoperative cervical length or the time interval between operation (OP)-preterm prelabour rupture of fetal membranes (PPROM). Secondary outcomes were neonatal complications and maternal complications due to the procedure. Statistical analysis was performed using the program SPSS 22. A p-value of <.05 was considered statistically significant.Results: Mean gestational age (GA) at OP of group 1 (20.3 ± 3 GW) was comparable with group 2 (21.5 ± 2.4 GW; p = .27). The GA at birth was significantly higher in group 1 (31.5 ± 5.9 GW) than in group 2 (27.0 ± 4.7 GW: p = .02). The survival rate of at least one child at 30 days and 6 months of age was 81% in group 1 and only 60% in group 2 (p = .1). PPROM <32 GW occurred in 43%. The survival rate of at least one child was significantly higher if the OP-PPROM interval was >28 days (93 versus 43%; p = .02). Major brain injury was observed in 11% of infants. Severe maternal complications (pulmonary edema) occurred in three cases (8%).Conclusions: Our survival rate of at least one child at 30 days and 6 months of age and the outcome of the mothers is well comparable to other international studies. A preoperative maternal cervical length of >25 mm and an occurrence of PPROM more than 28 days after the laser therapy is associated with a higher survival rate of at least one child at 6 months of age.

Open Intrauterine Fetal Myelomeningocele Repair: Changes in the Surgical Procedure and Perinatal Complications during the First 8 Years of Experience at a Single Center.

INTRODUCTION: Open fetal myelomeningocele (fMMC) repair is nowadays a therapeutic option in selected cases. We aimed to evaluate changes in maternal and fetal outcome after fMMC repair during the first 8 years of experience at a tertiary referral fetal medicine center in Switzerland. -Materials and Methods: Between 2010 and 2018, fMMC repair and delivery of the neonate via planned cesarean section was performed in 67 cases. Cases were retrospectively stratified into 2 groups: a "training phase" (TP) with supervision from an external surgeon during 11 operations (2010-2014, 15 cases) followed by an "experienced phase" (EP, 2014-2018, 52 cases); each phase lasted about 4 years. Both phases were compared with regard to various maternal and fetal outcome parameters. RESULTS: Analyses did not reveal differences between TP and EP in major outcome parameters such as gestational age at delivery, chorionic membrane separation, or the incidence of placental abruption. Although more complex surgical techniques were applied in EP (e.g., dermal closure using a rotational flap), surgery time was not different from TP. At the same time, surgical complications such as oligohydramnios (27 vs. 8%, p = 0.046) with MRI-confirmed leakage (13 vs. 4%, nonsignificant) and subchorionic hematoma (20 vs. 2%, p = 0.009) were less common in EP than TP. CONCLUSIONS: This study shows that the level of competence at our center with regard to major perinatal outcome parameters was already high in the first years of fMMC repair. However, more complex surgical techniques and significantly less minor complications were observed during the most recent years.

Clinical and Histologic Evaluation of the Hysterotomy Site and Fetal Membranes after Open Fetal Surgery for Fetal Spina Bifida Repair.

INTRODUCTION: Among the risks associated with open fetal surgery, myometrium and fetal membrane issues are vexing problems since they may lead to uterine dehiscence or preterm premature rupture of membranes resulting in uterine rupture or preterm birth or both. The aim of this study was to examine whether stapled and sutured hysterotomy scars demonstrate partial or complete healing. METHODS: Hysterotomy sites after open fetal surgery were clinically evaluated in 36 women during Caesarean section, classified into the categories intact, thin, and partially or completely dehiscent, then completely excised and histologically analyzed in 25 cases. The histological examination focused on wound healing of myometrium and fetal membranes. RESULTS: The myometrium was intact, thin, and partially or completely dehiscent in 33, 58, and 9%, respectively. The interval between myelomeningocele repair and delivery did not correlate with the healing process. The myometrium showed a reparative zone (scar) with adjacent avital myometrium tissue, fibrosis, and inflammation with foreign body reaction. The intact myometrium was below 1 mm thickness in 56%. All fetal membranes showed complete dehiscence; in 41% they were completely avital. CONCLUSION: Our study provides evidence that the myometrium shows scarring with substantial thinning or dehiscence. Fetal membranes do not heal spontaneously. In order to prevent uterine rupture in subsequent pregnancies, we recommend the hysterotomy site to be completely excised after birth.

High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power.

OBJECTIVE: The objective of this study was to determine for the first time the reliability and the diagnostic power of high-resolution microarray testing in routine prenatal diagnostics. METHODS: We applied high-resolution chromosomal microarray testing in 464 cytogenetically normal prenatal samples with any indication for invasive testing. RESULTS: High-resolution testing revealed a diagnostic yield of 6.9% and 1.6% in cases of fetal ultrasound anomalies and cases of advanced maternal age (AMA), respectively, which is similar to previous studies using low-resolution microarrays. In three (0.6%) additional cases with an indication of AMA, an aberration in susceptibility risk loci was detected. Moreover, one case (0.2%) showed an X-linked aberration in a female fetus, a finding relevant for future family planning. We found the rate of cases, in which the parents had to be tested for interpretation of unreported copy number variants (3.7%), and the rate of remaining variants of unknown significance (0.4%) acceptably low. Of note, these findings did not cause termination of pregnancy after expert genetic counseling. The 0.4% rate of confined placental mosaicism was similar to that observed by conventional karyotyping and notably involved a case of placental microdeletion. CONCLUSION: High-resolution prenatal microarray testing is a reliable technique that increases diagnostic yield by at least 17.3% when compared with conventional karyotyping, without an increase in the frequency of variants of uncertain significance.

Prenatal diagnosis and postnatal outcome of fetal spinal defects without Arnold-Chiari II malformation.

OBJECTIVE: To determine the prenatal evolution/natural history and postnatal outcome of fetuses diagnosed with a neural tube defect (NTD) lacking the Arnold-Chiari-II malformation (ACM II). MATERIAL AND METHODS: This retrospective study reviewed 16 fetuses evaluated with ultrasound (US) and MRI at a single referral center from 1/2000 to 8/2007. Follow-up studies and available postnatal outcomes were reviewed. RESULTS: Postpartum diagnosis was terminal myelocystoceles 7/16 (44%); myelomeningoceles (MMCs) 3/16 (19%); lipomyelomeningoceles 2/16(13%); and thoracic myelocystocele 1/16 (6%). Three patients (19%) were lost to follow-up or termination of pregnancy. Two prenatally diagnosed 'closed' NTD were postnatally found to be MMCs. Three of the myelocystoceles had additional omphalocele, bladder extrophy, imperforate anus and spinal defect (OEIS complex). For the total cohort, impaired lower extremity function was seen in 38%, impaired bladder function in 64%, and ventriculoperitoneal shunting in 8%. Four fetuses with a myelocystocele developed hindbrain herniation in the third trimester of pregnancy. The preterm delivery rate was 38%. Five of eight (63%) neonates with postnatally diagnosed myelocystoceles had mothers with a body mass index over 30. CONCLUSION: Prenatal differentiation between closed and open NTD is not always possible. Postnatal outcome of isolated myelocystocele and MMC seems to be more favorable than for an NTD with ACM II (shunt requirement). Incontinence is the major childhood morbidity. Maternal obesity may be a risk factor for closed NTDs.

When is fetoscopic release of amniotic bands indicated? Review of outcome of cases treated in utero and selection criteria for fetal surgery.

OBJECTIVES: The objectives are to analyze the outcomes of fetal interventions for fetal limb abnormalities associated with amniotic band syndrome (ABS), to compare the outcome with the known natural history, and to establish selection criteria for fetal intervention. MATERIAL AND METHODS: In a Medline search, six cases of prenatal fetoscopic interventions for ABS were found. An unpublished case was added. RESULTS: Review of the seven cases of treated ABS in utero suggests that abnormal, but present blood flow at Doppler distal to the area constricted by the band may optimally identify cases suitable for fetal surgery. We propose a prenatal classification in stages of cases of ABS based on ultrasound and Doppler findings. Premature rupture of membranes (PROM) occurred in five patients (71%). The median gestational age (GA) at delivery was 34.8 weeks (range 32 to 39). The median time between procedure and PROM was 6 weeks (range 4 days to 14.3 weeks). The median time between procedure and delivery was 11.8 weeks (range 5-17). CONCLUSION: The use of a uniform prenatal classification of cases of ABS may allow a more precise correlation of prenatal findings and postnatal outcome.

Prenatally diagnosed fetal lung lesions with associated conotruncal heart defects: is there a genetic association?

UNLABELLED: Congenital lung malformation can easily be diagnosed by prenatal ultrasound. Associated extrapulmonary malformations such as heart defects and chromosomal aberrations are rare. OBJECTIVE: The objective of this study was to describe the natural history, outcome and other associated malformations in fetuses with lung lesions and an associated heart defect. METHODS: Retrospective analysis of 4 cases of prenatally diagnosed fetal CCAMs and hybrid lesions with an associated heart defect and review of 8 cases in the literature. RESULTS: At a single referral center 1.9% of the fetuses with Congenital cystic adenomatoid malformation (CCAM) were diagnosed with an associated heart defect. Seven of the total 12 cases (58%) reviewed had a conotruncal heart abnormality. Chromosomal abnormalities were found in 5 (42%) of the cases. CONCLUSION: This retrospective review shows that karyotyping in fetal lung lesions with an associated heart defect or isolated large lung lesions is indicated. It also suggests that there is a subpopulation of fetuses with CCAMs who have conotruncal heart defects. This finding may suggest a common genetic background.