Ramen H. Chmait

Prospective Observational Study to Establish Predictors of Glyburide Success in Women with Gestational Diabetes Mellitus

OBJECTIVE: To establish parameters associated with therapeutic success in gestational diabetics treated with glyburide.STUDY DESIGN: A total of 69 gestational diabetics who failed dietary therapy were treated with glyburide. Inadequate glycemic control on maximum dose glyburide (10 mg b.i.d.) was considered treatment failure. The glyburide failure rate was calculated and factors that might predict success with glyburide were analyzed between the success and failure groups using χ2 or Studentst-tests.RESULTS: The glyburide failure rate was 18.8%. Gestational age at glyburide initiation (p<0.01), pretreatment fasting blood sugars (p<0.001), and 1-hour postprandial values (p<0.001) were the only statistically significant factors between the two groups. Glyburide success was predicted if dietary failure occurred after 30 weeks, or fasting blood sugars were <110 mg/dl and 1-hour postprandials were <140 mg/dl (sensitivity 98%, specificity 65%).CONCLUSION: Gestational diabetics who fail dietary therapy after 30 weeks gestation or have fasting blood sugars <110 mg/dl and 1-hour postprandials <140 mg/dl do well on glyburide therapy.

Sequential selective laser photocoagulation of communicating vessels in twin–twin transfusion syndrome

Objective. We have previously described the selective laser photocoagulation of communicating vessels (SLPCV) technique for the treatment of twin–twin transfusion syndrome (TTTS). Because TTTS is thought to result from a net transfer of blood from the donor twin to the recipient twin, we hypothesized that lasering the arteriovenous anastomoses from the donor to the recipient (AVDRs) first (sequential SLPCV or SQLPCV) would result in an improved hemodynamic status and decreased likelihood of intrauterine fetal demise of the donor twin (IUFD-D). Materials and methods. The diagnosis of TTTS was made by ultrasound showing the combined presence of a maximum vertical pocket ≥ 8 cm in one sac and ≤2 cm in the other in a monochorionic/diamniotic twin pregnancy. Triplet pregnancies and monoamniotic pregnancies were excluded. Severity of TTTS was assessed using the Quintero staging system. All vascular anastomoses were endoscopically identified and classified as AVDR (AV from donor to recipient), AVRD (AV from recipient to donor), arterio-arterial (AA), or veno-venous (VV). The surgical procedure was coded as SQLPCV if all AVDRs were lasered first. Outcome measures included intrauterine fetal demise and perinatal survival. Results. One hundred and ninety-three TTTS patients (137 SQLPCV, 56 SLPCV) underwent surgery from May 2003 to August 2005. Gestational age at surgery or at delivery, Stage, patent anastomoses, or persistent/reverse TTTS were not different between the groups. IUFD-D was significantly lower in the SQLPCV than in the SLPCV group (7.3% vs 21.4%, respectively, p = 0.005). Dual perinatal survival was significantly higher in the SQLPCV than in the SLPCV group (73.7% vs 57.1%, respectively, p = 0.02), although the incidence of at least one survivor was not different between the groups (90.5% vs 87.5%, respectively). Logistic regression showed SQLPCV, but not placental location, operating time or number of anastomoses to be significantly associated with a decreased likelihood of IUFD-D (p = 0.007). Conclusion. SQLPCV is associated with a decreased likelihood of IUFD-D and an increased rate of dual survivors compared to SLPCV. SQLPCV represents both an anatomical and functional surgical approach to the laser treatment of twin–twin transfusion syndrome.

Stage-based outcomes of 682 consecutive cases of twin–twin transfusion syndrome treated with laser surgery: the USFetus experience

OBJECTIVE We sought to describe stage-specific perinatal outcomes after selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome. STUDY DESIGN Patients with twin-twin transfusion syndrome underwent SLPCV preferentially using sequential vs standard laser technique. Patient characteristics and outcome data were examined by Quintero stage. RESULTS Of 682 consecutive women studied, the Quintero stage distribution was: 114 stage I (17%), 177 stage II (26%), 328 stage III (48%), and 63 stage IV (9%). Perinatal survival of at least 1 twin did not differ according to stage (I-92%, II-93%, III-88%, IV-92%; P = .30). However, dual twin survival differed by stage (I-79%, II-76%, III-59%, IV-68%; P < .01), primarily because stage III pregnancies were associated with decreased donor twin survival (P < .01). Sequential SLPCV was associated with improved donor survival, independent of stage (odds ratio, 1.67; 95% confidence interval, 1.16-2.40; P < .01). CONCLUSION Stage-specific perinatal outcomes after laser therapy may assist physicians in patient counseling and in planning future studies.

Neurodevelopmental outcomes after laser therapy for twin-twin transfusion syndrome: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review of the literature regarding the occurrence of neurologic morbidity, neurologic impairment, or neurologic morbidity and impairment of patients treated with laser therapy for twin–twin transfusion syndrome. DATA SOURCES: The PubMed, MEDLINE, EMBASE databases and reference lists were searched up to December 2010 for studies describing outcomes in laser-treated twin–twin transfusion syndrome pregnancies. METHODS FOR STUDY SELECTION: Inclusion criteria were twin–twin transfusion syndrome diagnosed with standard criteria and treated by laser therapy and neurologic morbidity and neurologic impairment collected at birth or 28 days after birth. Exclusion criteria were omission of at least one criterion; data in graphs or percentage; and non-English publications, letters, personal communications. TABULATION, INTEGRATION AND RESULTS: Data recorded were rates and length of successful follow-up, age at diagnosis and type of neurologic morbidity, affected donors and recipients, prevalence of neurologic morbidity, and neurologic impairment for twin sets. From 15 articles, the incidence of neurologic morbidity at birth was 55 out of 895 (6.1%), without differences between donors and recipients (19/249, 7.6% compared with 16/273, 5.8%; odds ratio [OR] 1.36; 95% confidence interval [CI] 0.68–2.70). At follow-up, the incidence of neurologic impairment was 140 out of 1,255 (11.1%), with cerebral palsy the most frequent (60/151, 39.7%). Neurologic impairment was identified equally between donors and recipients (48/330, 14.5% compared with 54/364, 14.8%; OR 1.02; 95% CI 0.66–1.57), and between one survivor and two survivors for twin sets (24/139, 17.3% compared with 88/489, 18.0%; OR 0.67; 95% CI 0.18–2.49). CONCLUSION: A small number (11.1%) of cases of twin–twin transfusion syndrome treated with laser therapy are affected with neurologic impairment that manifests during infancy. A strict follow-up of apparently healthy neonates is warranted.

Neonatal outcomes of twins according to birth order, presentation and mode of delivery: a systematic review and meta‐analysis*

Please cite this paper as: Rossi A, Mullin P, Chmait R. Neonatal outcomes of twins according to birth order, presentation and mode of delivery: a systematic review and meta‐analysis. BJOG 2011;118:523–532.

Endoscopic surgery for the antenatal treatment of myelomeningocele: the CECAM trial

BACKGROUND A recent randomized clinical trial named Management of Myelomeningocele Study (MOMS trial) showed that prenatal correction of open spina bifida (OSB) via open fetal surgery was associated with improved infant neurological outcomes relative to postnatal repair, but at the expense of increased maternal morbidity. OBJECTIVE We sought to report the final results of our phase I trial (Cirurgia Endoscópica para Correção Antenatal da Meningomielocele [CECAM]) on the feasibility, safety, potential benefits, and side effects of the fetoscopic treatment of OSB using our unique surgical technique. STUDY DESIGN Ten consecutive pregnancies with lumbosacral OSB were enrolled in the study. Surgeries were performed percutaneously under general anesthesia with 3 ports and partial carbon dioxide insufflation. After appropriate surgical positioning of the fetus, the neuroplacode was released with scissors and the skin was undermined to place a biocellulose patch over the lesion. The skin was closed over the patch using a single running stitch. Preoperative, postoperative, and postnatal magnetic resonance imaging were performed to assess hindbrain herniation. Neurodevelopmental evaluation was performed before discharge and at 3, 6, and 12 months. All cases were delivered by cesarean delivery, at which time the uterus was assessed for evidence of thinning or dehiscence. RESULTS The median gestational age at the time of surgery was 27 weeks (range 25-28 weeks). Endoscopic repair was completed in 8 of 10 fetuses. Two cases were unsuccessful due to loss of uterine access. The mean gestational age at birth was 32.4 weeks with a mean latency of 5.6 weeks between surgery and delivery (range 2-8 weeks). There was 1 fetal and 1 neonatal demise, and 1 unsuccessful case underwent postnatal repair. Of the 7 infants available for analysis, complete reversal of hindbrain herniation occurred in 6 of 7 babies. Three babies required ventriculoperitoneal shunting or third ventriculostomy. Functional motor level was the same or better than the anatomical level in 6 of 7 cases. There was no significant maternal morbidity and no evidence of myometrial thinning or dehiscence. However, surgeries were complicated by premature rupture of membrane and prematurity. CONCLUSION Our study suggests that the antenatal treatment of OSB using a fetoscopic approach and our unique surgical technique can result in a watertight seal, reversal of the hindbrain herniation, and better than expected motor function. Our technique differs substantially from the classic repair of OSB used in prior open fetal surgery and fetoscopic studies, in which the dura mater is dissected and the defect is closed in multiple layers. Instead, we use a biocellulose patch placed over the lesion and simple closure of the skin. As such, our technique is an alternative to the current paradigms in the antenatal treatment of OSB. Our clinical outcomes are in line with the results of our extensive prior animal work. Maternal benefits of our approach and technique include minimal morbidity and no myometrial legacy. Current limitations of the approach include potential loss of access, premature rupture of membranes, and attendant prematurity. Phase II trials are needed to prevent these complications and to further assess the risks and benefits of our distinct surgical approach and technique.

Ultrasound assessment of venous blood flow before and after laser therapy: approach to understanding the pathophysiology of twin–twin transfusion syndrome

To estimate direction and volume of blood exchange between the donor twin and recipient twin by ultrasound assessment of blood flow in the umbilical vein before and after selective laser photocoagulation of communicating vessels (SLPCV) for twin–twin transfusion syndrome (TTTS).

Fetoscopic single-layer repair of open spina bifida using a cellulose patch: preliminary clinical experience.

Abstract Objective: To report our preliminary clinical experience in the antenatal correction of open spina bifida (OSB) using a fetoscopic approach and a simplified closure technique. Methods: Four fetuses with lumbar-sacral defects were operated in utero from 25 to 27 weeks. Surgeries were performed percutaneously under general anesthesia using three trocars and partial carbon dioxide insufflation. After dissection of the neural placode, the surrounding skin was closed over a cellulose patch using a single continuous stitch. Results: Surgical closure was successful in three of the four cases. All successful cases showed improvement of the hindbrain herniation and no neonatal neurosurgical repair was required in two cases. Delivery occurred between 31 and 33 weeks, and no fetal or neonatal deaths occurred. Ventriculoperitoneal shunting was not needed in two out of the 3 successful cases. Conclusions: Our preliminary experience suggests that definitive fetoscopic repair of OSB is feasible using our innovative surgical technique. A phase I trial for the fetoscopic correction of OSB with this technique is currently being conducted.

Perinatal survival following preferential sequential selective laser surgery for twin-twin transfusion syndrome.

Objective. To describe our experience with preferential use of sequential selective laser photocoagulation of communicating vessels (SQLPCV) in women with twin-twin transfusion syndrome (TTTS). Methods. Women with TTTS received treatment using the SQLPCV technique whenever possible. SQLPCV mandates ablation of all donor-to-recipient arteriovenous communications first, in comparison to the standard non-sequential selective technique. Results. Of 99 consecutive women treated, 64 received SQLPCV. Overall survival of one or both twins was 91% and dual survival was 72%. Higher dual survival rates (80 vs. 57%, p = 0.0317) and donor survival rates (83 vs. 63%, p = 0.0489) were noted in the SQLPCV group. Multivariable logistic regression demonstrated that the SQLPCV technique was highly associated with dual survivorship (OR = 4.64 [1.57–13.74], p = 0.0056), when controlling for gestational age at surgery, duration of laser treatment and number of anastomoses lasered. Neither Quintero stage, placental location, preoperative discordance prior to surgery, nor preoperative cervical length contributed to this equation. The SQLPCV technique was also associated with donor survivorship (OR = 4.43 [1.44–13.67], p = 0.0095), when controlling for the same covariates. Conclusion. Treatment of TTTS via SQLPCV technique was associated with higher dual survival and donor twin survival rates as compared to standard SLPCV.

Chimerism in monochorionic dizygotic twins: Case study and review

Chimerism occurs when an organism contains cells derived from more than one distinct zygote. We focus on monochorionic dizygotic twin blood chimerism, and particularly twin–twin transfusion syndrome in such pregnancies. For years, researchers have understood chimerism to be a common phenomenon in cattle. Although, this review will not delve deeply into animal chimerism, an understanding of chimerism in the animal world can provide clues regarding health implications for human chimeras. This report serves two purposes: an update and assessment of the twins we reported previously in 2010 [Assaf et al., 2010] and a review on dizygotic monochorionic chimeric twins. First, our updated assessment of the twins shows no identifiable regression of Müllerian sex derivatives in the female, and normal neurodevelopment was documented in both. Our research has suggested several key points; one that blood chimerism persists from fetal life to at least age two years. Second, chimerism in humans is not as rare as previously thought, although it has been studied only recently. Third, assisted reproductive technologies appear to increase the risk of monochorionic dizygotic twin pregnancies.