Randall S. Kuhlmann

Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome☆☆☆

OBJECTIVE We undertook a pilot study to determine the feasibility and efficacy of fetoscopic laser occlusion of chorioangiopagous vessels in severe previable twin-twin transfusion syndrome. STUDY DESIGN A total of 35 patients were referred to the investigators with ultrasonographic findings consistent with twin-twin transfusion syndrome, posterior placental implantation, gestational age < 25 weeks, and clinical hydramnios. Placental vessel occlusion was performed with a rigid 2.9 x 3.85 mm dual-channel fetoscope and neodymium:yttrium-aluminum-garnet laser light. RESULTS Of the original 35 patients, 5 were eliminated preoperatively and 4 intraoperatively for various factors. The 26 treated patients had a mean gestational age of 20.8 weeks (range 18 to 24) and a mean fundal height of 36.1 cm (range 29 to 44). One patient has surviving triplets, 8 have surviving twins, 9 have a single survivor (2 neonatal and 7 fetal deaths occurred in this group), and 8 have no survivors (all had pregnancy loss within 3 weeks of treatment). The cases with survivors were delivered for obstetric indications at a mean of 32.2 weeks (range 26 to 37), having gained a mean of 11.7 weeks (range 6 to 17) in utero. Fifty-three percent (28/53) of the fetuses survived with 96% (27/28) developing normally at a mean age of 35.8 months (range 1 to 68). Thirty-three of 35 placentas were monochorionic with chorioangiopagous vessels on gross and microscopic evaluation. CONCLUSIONS Fetoscopic laser occlusion of chorioangiopagous vessels is technically feasible and improves the course and outcome of severe twin-twin transfusion syndrome in previable fetuses.

Treating previable twin-twin transfusion syndrome with fetoscopic laser surgery : outcomes following the learning curve

Abstract Aims: We have performed fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) in previable pregnancies affected by twin-twin transfusion syndrome (TTTS) since 1988. Treatment outcomes obtained after the procedures learning curve are presented and compared to those from other centers performing FLOC or other treatment methods. Methods: A total of 100 cases of FLOC have been performed at our centers. The later 67 TTTS patients had a mean gestational age of 21.1 ± 1.7 weeks (range 18–24.5) with a mean fundal height of 33.1 ± 4.9 cm (range 27–44) when treated. Eighteen (27 %) had failed another treatment method before FLOC. Results: All 67 cases have delivered with 82% (55/67) having at least one surviving twin and 93/134 (69 %) of the twins surviving overall. Thirty-eight have surviving twins, 17 have one survivor (5 neonatal and 12 fetal deaths), and 12 have none. The mean duration of pregnancy following FLOC was 9.9 ± 5.5 weeks (range 1.0–19). Only 4 of 93 (4.3 %) survivors have significant handicaps at a mean follow-up of 14.3 ± 10.1 months (range 1.0–34). Conclusion: Fetoscopic laser occlusion of chorioangiopagous vessels within the vascular equator limits the duration of fetal pathophysiology in TTTS and results in neonatal outcomes superior to the modified procedure and other treatment methods.

Budesonide induction and maintenance therapy for Crohn's disease during pregnancy

Background: There is no standard approach for the medical management of Crohns disease (CD) during pregnancy and there is limited data regarding safety and efficacy of the treatments. Budesonide (Entocort® EC, AstraZeneca) is an enteric coated locally acting glucocorticoid preparation whose pH‐ and time‐dependent coating enables its release into the ileum and ascending colon for the treatment of mild to moderate Crohns disease. There is no available data on the safety of using oral budesonide in pregnant patients. Methods: We reviewed our Inflammatory Bowel Disease (IBD) center database to identify patients with CD who received treatment with budesonide for induction and/or maintenance of remission during pregnancy and describe the maternal and fetal outcomes in a series of eight mothers and their babies. Results: The mean age of the patients was 27.7 years. All patients had small bowel involvement with their CD. The disease pattern was stricturing in 6 patients, fistulizing in 1 and inflammatory in 1 patient. Budesonide was used at the 6 mg/day dose in 6 patients and 9 mg/day dose in 2 patients. The average treatment duration ranges from 1‐8 months. There were no cases of maternal adrenal suppression, glucose intolerance, ocular side effects, hypertension or fetal congenital abnormalities. Conclusion: Budesonide may be a safe option for treatment of CD during pregnancy.

Diamnionic monochorionic twin gestations: an overview.

Monochorionic (MC) twins account for about 20-30% of all twins, but contribute disproportionately to mortality, intrauterine growth restriction, and preterm delivery compared with dichorionic (DC) twins. This higher mortality in MC twins is likely due to the effects of placental morphologic characteristics, which include complex vascular communications between the twins associated with twin-twin transfusion syndrome (TTTS), and the tendency for the common placenta to be shared either symmetrically or asymmetrically. In assessment of clinical outcomes for TTTS, artery to vein anastomoses in the absence of artery to artery or vein to vein, especially if present with placental asymmetry, carry the worse prognosis. Chorion status in twins forms the basis for clinical risk assessment and can be determined by 7 menstrual weeks using transvaginal sonography. The variable results reported in the literature for intertwin umbilical artery Doppler findings in MC twins may be explained by differences between sonographic and clinical criteria (including differential hemoglobin concentrations) reported by various investigators. Antenatal fetal Doppler assessment of the umbilical artery and cerebral arteries can help distinguish between TTTS and placental insufficiency in MC twins. Significant restriction of fetal growth occurs in about 25% of multiple gestations, accounting for about 17% of all growth-retarded infants. Redistribution of fetal blood (brain-sparing effect), as determined by Doppler interrogation of fetal cerebral and umbilical arteries, occurs more commonly in MC twins compared to DC twins and in growth-restricted MC twins compared to nongrowth-restricted MC twins. Overall, the prognosis is poorer for the donor twins in TTTS and there is a greater prenatal death rate for the donor (18-35%), and a higher overall survival rate for recipients following fetoscopic laser treatment. Finally, the clinical and sonographic findings suggest that the polyhydramnios/oligohydramnios sequence seen in MC twins likely represents a spectrum strongly linked to placental variables.

Cardiovascular teratogenicity of terbutaline and ritodrine in the chick embryo

OBJECTIVE We determined the teratogenic effects of terbutaline and ritodrine, both beta 2-sympathomimetic agonists, on the stage 24 (4-day) chick embryo. STUDY DESIGN We used a topical method of application of terbutaline or ritodrine to the stage 24 chick embryo in ovo. Doses of terbutaline ranged from 5.5 x 10(-10) to 6.5 x 10(-9) mol per embryo, and ritodrine doses ranged from 4.6 x 10(-11) to 4.6 x 10(-8) mol per embryo. To further determine the pharmacologic nature of the teratogenic potential of terbutaline or ritodrine, the experiments were repeated after pretreatment with butoxamine hydrochloride, a preferential beta 2-antagonist, or metoprolol tartrate, a preferential beta 1-antagonist, 4 hours before application of terbutaline or ritodrine. RESULTS Terbutaline treatment was associated with significantly higher rates of anomalies than in controls at all dosages used, whereas ritodrine induced significantly more anomalies at or above doses of 4.6 x 10(-9) mol per embryo. At an equimolar dose pretreatment with butoxamine hydrochloride significantly reduced the cardiovascular teratogenic effects of terbutaline and ritodrine. Pretreatment with metoprolol tartrate at any dose did not significantly reduce terbutalines potential. Metoprolol, at doses tenfold or 100-fold higher than ritodrine, was able to significantly reduce the teratogenic effects of ritodrine. CONCLUSIONS Our data suggest that terbutaline and ritodrine are teratogenic in the chick and that these agents exert their teratogenic effects primarily through stimulation of the beta 2-adrenergic receptor.

Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.

Tissue and plasma levels of a teratogenic dose of dopamine in the chick embryo following pretreatment with metoprolol or phosphate buffered saline

Metoprolol pretreatment has been shown to reduce the cardiovascular malformation rate produced by topical doses of dopamine in the stage 24 chick embryo. We report on the tissue and plasma levels and teratogenic effect of dopamine hydrochloride following topical application of a teratogenic dose in stage 24 chick embryos pretreated with either metoprolol tartrate or phosphate buffered saline (PBS). Pretreatment with either metoprolol or PBS resulted in similar patterns of dopamine distribution in the head, body, and heart, with peak levels occurring at 12 hours after dopamine treatment. Plasma concentrations of dopamine were similar for both PBS and metoprolol pretreated embryos, with plasma levels exceeding tissue concentrations, but also peaking at 12 hours after dopamine treatment. Pretreatment with PBS followed by a teratogenic dose of dopamine resulted in a decrease in the teratogenic effect of dopamine similar to that found in previous work in our lab with pretreatment with metoprolol. The developing chick cardiovascular system experiences peak susceptibility to the teratogenic effects of dopamine at stage 24 during development, which represents a time frame of about 12 hours. A delay in the peak levels of dopamine to 12 hours after dopamine treatment as compared to previous work in our lab reporting peak levels of dopamine at 1 hour, suggests that the previously reported antiteratogenic effects of metoprolol may be due, at least in part, to a delayed absorption of dopamine past the time of peak susceptibility of the embryo to the teratogen.

Twin-to-twin transfusion syndrome--30 years at the front.

Thirty years ago, twin-to-twin transfusion syndrome (TTTS) was one of the most challenging problems of modern obstetrics. The associated mortality and morbidity was staggering, and a sense of hopelessness prevailed among clinicians and pediatric pathologists. Technical advances in ultrasound, endoscopy, video recording, and medical lasers formed the basis for diagnosis and in utero therapy of placental disorders. We review some historical events which gave rise to a new treatment modality for TTTS, fetoscopic laser occlusion of chorioangiopagous vessels, now the most common operation performed worldwide in behalf of fetuses in peril.

First-Trimester Embryology: An Overview

Normal human development is a continuum. However, unfortunate interruptions in this ongoing process can result in abnormal development and subsequent congenital anomalies. These anomalies can be the result of many etiologic factors. Approximately 3 % or greater of pregnancies are complicated by congenital anomalies. The purpose of this chapter is to provide the clinician or sonographer with the essential basics of embryological and fetal development, to better understand mechanisms of normal and abnormal first-trimester human development. Understanding of these mechanisms is imperative for adequate evaluation of the first-trimester fetus in the ultrasound laboratory.

Percutaneous in utero thoracoamniotic shunt creation for fetal thoracic abnormalities leading to nonimmune hydrops.

PURPOSE To describe a transabdominal, transuterine Seldinger-based percutaneous approach to create a shunt for treatment of fetal thoracic abnormalities. MATERIALS AND METHODS Five fetuses presented with nonimmune fetal hydrops secondary to fetal thoracic abnormalities causing severe mass effect. Under direct ultrasound guidance, an 18-gauge needle was used to access the malformation. Through a peel-away sheath, a customized pediatric transplant 4.5-F double J ureteral stent was advanced; the leading loop was placed in the fetal thorax, and the trailing end was left outside the fetal thorax within the amniotic cavity. RESULTS Seven thoracoamniotic shunts were successfully placed in five fetuses; one shunt was immediately replaced because of displacement during the procedure, and another shunt was not functioning at follow-up requiring insertion of a second shunt. All fetuses had successful decompression of the thoracic malformation, allowing lung reexpansion and resolution of hydrops. Three of five mothers had meaningful (> 7 d) prolongation of their pregnancies. All pregnancies were maintained to > 30 weeks (range, 30 weeks 1 d-37 weeks 2 d). There were no maternal complications. CONCLUSIONS A Seldinger-based percutaneous approach to draining fetal thoracic abnormalities is feasible and can allow for prolongation of pregnancy and antenatal lung development and ultimately result in fetal survival.