Successful intra-amniotic levothyroxine treatment for fetal goitrous hypothyroidism in a triplet pregnancy.

We report an extremely challenging case of fetal goitrous hypothyroidism involving all three fetuses of a triplet pregnancy in which successful fetal treatment led to a favorable pregnancy outcome. The patient had a trichorionic, triamniotic triplet pregnancy and was referred to us at 24 weeks gestation after goiters affecting all three fetuses and polyhydramnios involving two fetuses were noted. Immediately before the conception, she underwent hysterosalpingography with an oil-soluble iodinated contrast medium. After the diagnosis of fetal hypothyroidism was made, intra-amniotic injection of levothyroxine was performed for two fetuses with polyhydramnios 3 times between 28 and 31 weeks gestation. The goiters shrunk and the polyhydramnios improved in response to the in utero treatment. No complications occurred. Cesarean section was performed at 33 weeks gestation. None of the three neonates developed respiratory insufficiency. Our experience suggested that successful intrauterine treatment is possible for fetal goitrous hypothyroidism, even in a triplet pregnancy. The indication, treatment timing, and diagnostic and assessment strategies should be carefully discussed to minimize puncture-related complications.

Outcomes of fetoscopic laser surgery for twin-to-twin transfusion syndrome between 26 and 27 weeks of gestation in Japan.

AIM: The purpose of this study was to investigate the outcomes of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS) in Japan. METHODS: The retrospective cohort study (2012-2018) was conducted in monochorionic twin pregnancies that underwent FLP for TTTS between 26 and 27 weeks from 2012 to 2018. The perioperative data, maternal complications, gestational age (GA) at delivery, neonatal complications, and survival of infants at 28 days of age were analyzed. At term-equivalent age, severe neurological complications were identified by imaging study. RESULTS: Of 644 patients, 28 (4.3%) underwent FLP between 26 and 27 weeks, and 26 were analyzed. FLP procedures were technically successful in all cases. There were no cases of major maternal complications after surgery. Preterm rupture of membranes occurred in 34.6% of cases, and the mean GA at delivery was 33.2 ± 3.1 weeks. The survival of both twins was found in 23 (88.4%) cases, and the perinatal survival rate of at least one twin at 28 days of age was 100%. Severe neurological complications were found in six (12.2%) cases out of 49. CONCLUSIONS: FLP for TTTS between 26 and 27 weeks provided a good prognosis and caused no major maternal complications. However, severe neurological findings were found in 12% of infants.

Fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

The aim of this study was to review fetoscopic laser photocoagulation (FLP), which ablates placental vascular anastomoses to treat twin-twin transfusion syndrome (TTTS). A review of studies reporting on the procedures, outcomes, complications and nonconventional applications of FLP for TTTS was conducted. FLP has been established as the primary treatment for monochorionic twin pregnancy associated with TTTS at 16-26 weeks. FLP is the only therapy that directly addresses the underlying pathophysiology. The recent technique modification of FLP, referred to as the 'Solomon technique', induces selective coagulation to connect the anastomoses ablation sites and has been introduced to reduce residual anastomoses. The perinatal survival following FLP improved significantly with advances in the technique after its introduction. The recent survival rates of both twins and at least one twin are 70% and more than 90%, respectively. However, there is still an 11-14% risk of long-term neurodevelopment impairment. The premature rupture of membranes that leads to preterm labor is a common complication after FLP. FLP is a valuable treatment option for feto-fetal transfusion syndrome in triplets and for TTTS after 26 weeks. FLP for selective intrauterine growth restriction may be potentially beneficial when accompanied by abnormal Doppler findings and oligohydramnios. FLP is the optimal treatment option for TTTS at 16-26 weeks of gestation. FLP appears to be applicable in triplets, TTTS after 26 weeks and cases of selective intrauterine growth restriction with abnormal Doppler findings and oligohydramnios. FLP is the most common and successful fetal intervention. Improvement in the neurodevelopmental outcomes after FLP is a future focus.

Chorioamniotic Membrane Separation after Fetoscopic Laser Photocoagulation.

INTRODUCTION: This study aimed to investigate the risk factors, incidence, and influence on the perinatal outcome of chorioamniotic membrane separation (CMS) after fetoscopic laser photocoagulation (FLP). MATERIAL AND METHODS: This retrospective study included 312 women who underwent FLP for twin-to-twin transfusion syndrome (TTTS). Clinical records were used to review obstetrical examinations, complications, operative data, ultrasonographic findings, and perinatal and neonatal follow-up data in all patients. RESULTS: A total of 260 cases of TTTS were analyzed. The incidence of CMS was 12.7% (33 cases). The only independent risk factor of CMS was performing FLP before 20 weeks of gestational age (GA) (odds ratio = 3.38 [1.44-7.93], p = 0.005). Concerning perinatal outcome, CMS was only related with increased risk of premature rupture of membranes (PROM) before 32 weeks (33.3 vs. 13.9%, p = 0.005), with no differences in GA at delivery and survival rate. DISCUSSION: In our cohort, the incidence of CMS after FLP was approximately 13%, with surgery before 20 weeks being the only risk factor identified. Although in our population CMS did not worsen perinatal outcome in terms of preterm delivery or survival, the preterm PROM rate was increased and this should be considered for the patients' management.

Fetoscopic laser photocoagulation for amniotic fluid discordance bordering on twin-twin transfusion syndrome: Feasibility, perinatal and long-term outcomes.

AIM: This study investigated the feasibility and safety of fetoscopic laser photocoagulation (FLP) for amniotic fluid discordance (AFD) bordering on twin-twin transfusion syndrome (TTTS) with an absent or reverse end-diastolic velocity (AREDV) in the umbilical artery (UA), and evaluated the perinatal and long-term outcomes. METHODS: A prospective intervention study was performed between 20 + 0 and 25 + 6 weeks of gestation (UMIN000004165). AFD bordering on TTTS was defined as maximum vertical pocket (MVP) of amniotic fluid in one twin's sac ≤3 cm and amniotic fluid MVP in the other twin's sac ≥7 cm excluding TTTS. Neurodevelopmental outcome was evaluated at 6 months and at 3 years of age. RESULTS: Eleven women were treated without complications between September 2010 and July 2011. In all cases amnioinfusion was required, with a median surgical time of 70 min. There were nine cases of selective intrauterine growth restriction in which the growth discordant rate was >25%. The survival rates of the donor and recipient twins were 27.3% (3/11) and 100% (11/11), respectively. None of the surviving donor twins and two of the 11 recipient twins had hemiplegia at 6 months of age. One additional recipient twin had developmental delay at 3 years of age. CONCLUSIONS: Fetoscopic laser photocoagulation for AFD bordering on TTTS with AREDV in the UA was feasible without complications but frequently resulted in donor twin death and a high survival rate of the recipient twin, albeit with neurodevelopmental abnormalities in some cases. FLP does not seem to be a promising treatment option for AFD bordering on TTTS.

Forty cases of twin reversed arterial perfusion sequence treated with radio frequency ablation using the multistep coagulation method: a single-center experience.

OBJECTIVE: To report the pregnancy outcomes of patients with twin reversed arterial perfusion (TRAP) sequence treated by radiofrequency ablation (RFA). METHODS: This was a retrospective study of TRAP sequences treated in a single center between March 2002 and February 2015. Forty patients underwent RFA with expandable tines through a multistep coagulation method between 15 and 26 gestational weeks. The primary outcome was neonatal survival to discharge. RESULTS: The overall survival of the pump twin was 85%. The survival rates in monochorionic-monoamniotic (MCMA) pregnancies and monochorionic-diamniotic pregnancies were 66.7% (4/6) and 87.9% (29/33), respectively. One triplet was treated successfully and delivered at 36 weeks of gestation. One of 35 live births (2.9%) had preterm premature rupture of membranes less than 34 weeks, resulting in infant death. In five intrauterine pump twin deaths, two cases were MCMA twins with cord entanglement, and three cases were MCDA twins with acardius anceps. CONCLUSIONS: Our study supports the effectiveness of RFA for TRAP sequence after 15 weeks of gestation. The presence of MCMA twins or acardius anceps is associated with a high risk of pump twin death after RFA. © 2016 John Wiley & Sons, Ltd.

Analysis of antenatal-onset cerebral palsy secondary to transient ischemia in utero using a national database in Japan.

AIM: We conducted a retrospective analysis of summary medical reports of children diagnosed with cerebral palsy (CP) to identify clinical features of antenatal onset of CP secondary to transient ischemia in utero. METHODS: The 658 brief summary reports available in the Japan Obstetric Compensation System for Cerebral Palsy were screened, and we identified cases of singleton pregnancy, delivered at gestational age ≥ 33 weeks and those with cord blood gas pH ≥ 7.20. Of the 137 cases identified, 84 were excluded for the following reasons: no evidence of ischemic brain lesion, clear post-natal causative factor of CP, presence of a congenital condition, and sentinel hypoxic event, such as uterine rupture. The demographic profiles of the 53 cases included in our analysis were compared to identify those with and without an abnormal variability in fetal heart rate. RESULTS: Between-group comparison identified an association between abnormal heart rate variability and a lower Apgar score at 1 min (2 vs 6; P < 0.001) and 5 min (5.5 vs 8; P = 0.002), and more frequent episodes of fetal movement loss (41% vs 10%; P = 0.027). An hypoxic event ≤ 1 week before delivery was more likely to be associated with abnormal heart rate variability (89%) and low Apgar score (82%), while events at > 1 week were associated with development of polyhydramnios (44%). CONCLUSION: In utero transient ischemic events can contribute to term or near-term CP. Careful follow-up is recommended for fetuses with a history of fetal movement loss, abnormal variability in heart rate, and polyhydramnios of unknown causes.

Twin anemia-polycythemia sequence after laser surgery for twin-twin transfusion syndrome and maternal morbidity.

Twin anemia-polycythemia sequence (TAPS) is characterized by large inter-twin hemoglobin value differences without inter-twin amniotic fluid discordance. The management of post-laser TAPS remains controversial. Hence, more studies on TAPS, together with the associated maternal complications and outcome of the fetuses and infants are needed. Between 2003 and 2012, we performed 287 cases of fetoscopic laser photocoagulation for twin-twin transfusion syndrome. Among the 114 who were placed under our care until delivery, three cases of TAPS occurred. In one case, we conducted intrauterine intravenous transfusion, while in the other two cases, we adopted expectant management. We performed an emergency caesarean section at 27-30 weeks of gestation in all cases due to a severe condition of anemia in the TAPS donor. Two cases with antenatal TAPS stage 4 had severe maternal complications; one had minute pulmonary embolism, while the other had Mirror syndrome. All three pairs of infants survived. One TAPS donor and one TAPS recipient had neurodevelopmental impairment; bilateral deafness at 9.5 years old and spastic paralysis at 2 years old, respectively. In conclusion, post-laser TAPS in a higher stage can cause severe maternal complications. Close observations for both fetuses and mothers are required for such cases.

Thoracoamniotic shunting for fetal pleural effusions using a double-basket shunt.

OBJECTIVE: To describe the safety and efficacy of thoracoamniotic shunting for fetal pleural effusion using a double-basket catheter with a very small diameter (1.47 mm). METHOD: In this 2-year multicenter, prospective single-arm clinical study registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN00001095); shunting was performed between 18w0d and 33w6d of gestation with this catheter in cases of fetal pleural effusions reaccumulating after thoracocentesis. The primary endpoint measures were maternal and fetal adverse effects and survival in the neonatal period. RESULTS: A total of 24 cases were included, of which 17 had hydrops (71%). The median gestational ages at shunting and delivery were 27.4 and 34.8 weeks, respectively. There were no fetal deaths, lung injuries, or severe maternal complications. Preterm rupture of the membranes occurred in 7/24 (29%) cases at a median of 62 days after the shunting. Preterm rupture of the membranes within 28 days of the procedure occurred in 1/24 (4%) cases. Catheter displacement towards the fetal thoracic cavity occurred in 4/42 (10%) cases. The overall survival rate was 79% (19/24), whereas it was 71% (12/17) in the cases with hydrops. CONCLUSION: Drainage of fetal pleural effusions with a double-basket shunt is safe and effective, and the shunt could be an alternative device.

The Doppler cerebroplacental ratio predicts non-reassuring fetal status in intrauterine growth restricted fetuses at term.

AIM: To investigate whether cerebroplacental ratio (CPR) can be a useful marker to predict non-reassuring fetal status (NRFS) in small for gestational age (SGA) infants at term. MATERIAL AND METHODS: Three hundred and nine singleton SGA infants delivered between 37 and 41 weeks of gestation were included in this study. SGA infants were defined as birthweight less than 10th percentile for gestational age. Doppler measurements were recorded once a week until delivery. The incidence of NRFS or an emergency cesarean delivery, and relationship between CPR and NRFS in SGA infants were compared with appropriate for gestational age (AGA) infants at term, and a receiver-operator characteristics curve analysis was performed. RESULTS: The incidences of NRFS was significantly higher in SGA (27.8%) infants compared with in AGA infants (18.0%), and the rate of emergency cesarean delivery was significantly higher in SGA (14.6%) infants compared with AGA infants (8.3%). CPR was obtained from 63 SGA infants, and 16 out of 63 cases (25.4%) resulted in NRFS. The infants complicated with NRFS showed significantly lower CPR values compared with those without NRFS (1.05 ± 0.2 vs 1.23 ± 0.2, P = 0.013), while middle cerebral artery resistance index and 'umbilical artery resistance index were not statistically different between the two groups. A cut-off value of CPR 1.1 based on the receiver-operator characteristics curve provided the best combination with 62.5% sensitivity and 74.5% specificity to predict NRFS occurrence. CONCLUSIONS: The SGA infants complicated with NRFS showed significantly lower CPR values compared with those without NRFS.

Two cases of reversal of twin-twin transfusion syndrome diagnosed by measuring hourly fetal urine production.

Reversal of twin-twin transfusion syndrome (TTTS) is a rare complication of monochorionic pregnancy. Diagnostic criteria and satisfactory therapeutic options have not been reported. We make a suggestion of diagnosis and therapy for reversal of TTTS. We report two cases of reversal of TTTS. Measurement of the fetal urine production rate was useful for management and better comprehension of the cases. In case 1, double intrauterine fetal demise occurred before the criteria for TTTS were fulfilled, in which each fetal urine production rate reversed prior to the change of amniotic fluid volume. In case 2, elevated urine production was noted prior to progressive polyhydroamnios and congestive heart failure in the new recipient and the fetoscopic laser photocoagulation of the placental communicating vessels was performed successfully before the criteria for TTTS were fulfilled. Both infants required intensive care, but developed normally and showed no neurologic complications at 2 years after birth. Hourly fetal urine production rate was useful for immediate diagnosis of reversal of TTTS, and laser photocoagulation of the placental communicating vessels is thus a method for the correction of the fetal blood flow imbalance in cases of reversal of the donor-recipient phenotype in TTTS.

Perinatal outcome of monochorionic twins with selective intrauterine growth restriction and different types of umbilical artery Doppler under expectant management.

OBJECTIVES: To evaluate the prognosis of monochorionic twins with selective intrauterine growth restriction (sIUGR), classified according to the type of umbilical artery Doppler, under expectant management. METHODS: The outcome of 81 cases with isolated sIUGR was evaluated according to a classification based on umbilical artery (UA) Doppler diastolic flow in the IUGR twin (I: present, II: constantly absent/reverse, III: intermittently absent/reverse). Selective feticide was not considered due to legal constraints. Perinatal outcomes included perinatal death and neurological outcome at 6 months of age. RESULTS: From 81 cases with the diagnosis of sIUGR, twin-twin transfusion was diagnosed in 18 cases. This left 63 cases, of which 23 were classified as type I (36.5%), 27 as type II (42.9%) and 13 as type III (20.6%). Intrauterine death occurred in 4.3% (1), 29.6% (8) and 15.4% (2) among IUGR twins, and 4.3% (1), 22.2% (6) and 0.0% (0) among larger twins. Neonatal death occurred in 0.0% (0), 18.5% (5) and 0.0% (0) among IUGR twins, and 0.0% (0), 11.1% (3) and 23.0% (3) among larger twins. Neurological abnormalities at 6 months were found in 4.3% (1), 14.8% (4) and 23.1% (3) in smaller twins and 0.0% (0), 11.1% (3) and 38.5% (5) in larger twins, respectively. Intact survival at 6 months was recorded in 91% (21), 37% (10) and 61% (8) in smaller twins and 95% (22), 55% (15) and 38% (5) in larger twins, respectively. CONCLUSION: The outcome in monochorionic twins with sIUGR and abnormal umbilical artery Doppler is poor under expectant management. Normal Doppler seems to be associated with a good prognosis.

Therapeutic dilemma in twin reversed arterial perfusion sequence.

The dissemination of minimally invasive in utero surgery reduced the mortality of twin reversed arterial perfusion sequence, but the mortality of expectantly treated surgical candidates remains high. A 26-year-old, non-parous, Japanese woman at 13 weeks of gestation had been diagnosed with twin reversed arterial perfusion sequence and was judged as a surgical candidate for radiofrequency ablation. However, she did not undergo surgery because of the anatomical location of the acardiac twin. At 18 weeks of gestation, the blood flow to the acardiac twin disappeared spontaneously. The pump twin began to demonstrate fetal growth retardation during the third trimester. The patient delivered a 1891 g female at term. We macroscopically identified the cause of the fetal growth retardation as velamentous insertion of the umbilical cord and microscopically diagnosed the acardiac twin with acardiac acephalus. We should give the same attention to the management of post-twin reversed arterial perfusion sequence as twin reversed arterial perfusion sequence itself.

The experience of modified sequential selective laser photocoagulation of communicating vessels technique for twin-twin transfusion syndrome.

OBJECTIVE: Fetoscopic laser photocoagulation of vascular anastomoses (FLP) is the essential choice in twin-twin transfusion syndrome (TTTS). We proposed that the modified sequential selective laser photocoagulation of communicating vessels (modified SQLPCV) to clarify the perinatal outcomes in TTTS. METHODS: The modified SQLPCV was designed with the following order: 1, artery-to-artery anastomoses; 2, venous-to-venous anastomoses; 3, artery-to-venous anastomoses from donor to recipient; and 4, artery-to-venous anastomoses from recipient to donor. The perinatal outcomes were present in TTTS patients who underwent the modified SQLPCV. RESULTS: A total of 203 women underwent modified SQLPCV. The mean pregnancy prolongation period was 83 days, and the mean gestational age at delivery was 33 weeks (range 23-40 weeks). There was a significantly lower rate of recipient fetal demise than donor fetal demise (4% vs. 13%; p < .01). The survival rate of zero and one were respectively 6% (13/203) and 19% (39/203). Two survivors were seen in 74% (151/203), and at least one survivor in 94% (190/203). Univariate and multivariate analysis showed that abnormal fetal Doppler measurements in donor were correlated with donor demise after surgery. CONCLUSIONS: The modified SQLPCV represents satisfactory outcomes for fetuses complicating with TTTS.

Fetal Thoracoamniotic Shunting in a Case of Congenital Pulmonary Airway Malformations with Hydrops Fetalis.

Aim We report a case of congenital pulmonary airway malformation (CPAM) with hydrops in which the fetus underwent thoracoamniotic shunting. Case Report A 40-year-old (G1P1) woman was diagnosed with a macrocystic CPAM. Thoracoamniotic shunting was performed at 19 weeks of gestation but not well drained and was successfully performed again at 23 weeks. However, the CPAM volume ratio, abdominal circumference, and amniotic fluid index started increasing from 28 weeks and hydrops worsened. The insufficient shunting and the fetal cardiac failure had to be considered. At 32 weeks, a male infant with general edema and massive ascites was born weighing 3,362 g (+4.79 SD) with Apgar scores of 2 and 4. The infant was intubated and high-frequency oscillation and nitric oxide therapies were instituted. The resection of CPAM was performed on day 2. Nasal continuous positive airway pressure was instituted on day 16. The infant was discharged and prescribed with home oxygen therapy (HOT) on day 65. The infant was able to leave the HOT at 30 months and is currently 34 months of age in good condition. Conclusion Fetal thoracoamniotic shunting may be life-saving in CPAM complicated by hydrops and that this treatment might be sufficient to cure the child.

A prospective pilot study of fetoscopic laser surgery for twin-to-twin transfusion syndrome between 26 and 27 weeks of gestation.

OBJECTIVE: The aim of this study is to clarify the feasibility and efficacy of fetoscopic laser photocoagulation of placental vascular communicating vessels (FLP) on twin-twin transfusion syndrome (TTTS) after 26 weeks of gestation. MATERIALS AND METHODS: This is a prospective pilot study investigating all cases of TTTS between 26 weeks and 27 weeks during 2012 and 2013 in Japan. The primary endpoints in this study were the feasibility of FLP and rate of harmful complications for the mother's health. Also, perinatal prognosis was investigated. RESULTS: Six cases were enrolled and underwent FLP. Two of the six cases were classified preoperatively as Quintero Stage II and four cases were Stage III. FLP was completely achieved in all six cases. No severe maternal complications were noted during and immediately after the surgery. All but one case continued the pregnancies > 14 days after FLP. The median gestational age at delivery was 33.4 weeks (28.0-36.6 weeks). All 12 fetuses survived at the 28(th) day in the neonatal period. No case was diagnosed with cerebral lesion at the neonatal period. CONCLUSION: This prospective pilot study shows that FLP could be a therapeutic option for TTTS between 26 weeks and 27 weeks of gestation.

Ontogeny of gastric emptying patterns in the human fetus.

OBJECTIVE: Fetal swallowing and gastric emptying contribute importantly to amniotic fluid (AF) homeostasis and fetal gastrointestinal development. We speculated that fetal gastric emptying must be functional early in gestation to prevent rapid increases in AF. We sought to determine the human fetal ontogenic pattern of gastric emptying. STUDY DESIGN: Gastric emptying of eighty normal fetuses at 12-39 weeks was studied. Real-time ultrasound of the fetal stomach was continuously recorded for 1 hour. The gastric area ratio (GAR) was defined as the gastric area divided by the abdominal transverse area. The delta GAR was defined as the change between the maximum and the minimum gastric area ratiox100 (expressed as percent). A change of the fetal gastric area more than the 10th percentile of the delta GAR at 36-39 weeks was used to define gastric emptying. RESULTS: The 10th, 50th and 90th percentile of delta GAR at 36-39 weeks' was 5.2, 6.5 and 8.7%, respectively. Fetal gastric emptying was detected as early as 12 5/7 weeks of gestation. The proportion of fetuses demonstrating gastric emptying (>10th percentile delta GAR) increased with gestational age: 4/33 (12.1%) 12-23 weeks, 3/9 (33.3%) at 24-27 weeks, 8/11 (72.7%) at 28-31 weeks, 12/14 (85.7%) at 32-35 weeks, and 11/13 (84.6%) at 36-39 weeks. CONCLUSIONS: Fetal gastric emptying occurs by the beginning of the second trimester, contributing to AF regulation. The increased frequency of gastric emptying in late gestation is likely secondary to increased swallowing, altered fetal behavioral state or endogenous production of gastrointestinal motility factors.