Learning curves of open and endoscopic fetal spina bifida closure: a systematic review and meta-analysis

OBJECTIVES: The Management Of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida (SB). Recently developed alternative techniques may reduce maternal risks yet should do without compromising on fetal neuroprotective effects. We aimed to assess the learning curve of different fetal SB closure techniques. METHODS: We searched Medline, Web of Science, Embase, Scopus and Cochrane databases and the grey literature to identify relevant articles without language restriction from January 1980 until October 2018. We systematically reviewed and selected studies reporting all consecutive procedures and with a postnatal follow-up ≥12 months. They also had to report outcome variables necessary to measure the learning curve defined by fetal safety and efficacy. Two independent authors retrieved the data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effect model when heterogeneous. To measure the learning curve, we used two complementary methods. With the group splitting method, competency was defined when the procedure provided comparable results to the MOMS trial for 12 outcome variables representative for (1) the immediate surgical outcome, (2) short-term neonatal neuroprotection and (3) long-term neuroprotection at ≥12 months. Then, when the patients' raw data were available, we performed cumulative sum (CUSUM) analysis based on a composite binary outcome defining a successful surgery. It combined four clinically relevant variables for safety (fetal death within 7 days) and for efficacy (neuroprotection at birth). RESULTS: We included 17/6024 (0.3%) studies with low and moderate risks of bias. Fetal SB closure was performed via standard-hysterotomy (n=11), mini-hysterotomy (n=1) or fetoscopy [exteriorized-uterus single-layer (n=1), percutaneous single-layer (n=3) or percutaneous two-layer closure (n=1)]. Only outcomes for the standard-hysterotomy could be meta-analyzed. Overall, outcomes significantly improved with experience. Competency was reached after 35 consecutive cases for standard-hysterotomy and was predicted to be achieved after ≥57 cases for mini-hysterotomy and ≥56 for percutaneous two-layer fetoscopy. For percutaneous and uterus-exteriorized single-layer fetoscopy, competency was not respectively reached by cases 81 and 28 available for analysis. CONCLUSIONS: The number of cases operated correlates with the outcome of SB fetal closure and ranges from 35 cases for standard-hysterotomy to ≥56-57 cases for minimally invasive modifications. Our observations provide important information for institutions eager to establish a new fetal center, develop a new technique or train their team, and inform referring clinicians, potential patients and third-parties

Uterine artery Doppler patterns in abdominal pregnancy

Made available in DSpace on 2019-09-12T16:57:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Changes in the uterine artery blood flow waveform during pregnancy have been the subject of several studies and are frequently attributed to trophoblastic invasion of the myometrium. We report on a case of a third-trimester abdominal pregnancy in which we performed Doppler velocimetry of the uterine arteries and observed low-resistance flow and absence of notching bilaterally. During the 29th week of gestation, there was an increase in umbilical artery resistance and a decrease in the middle cerebral artery resistance, so we chose to deliver the baby at that stage. The patient was discharged from hospital 7 days following delivery and the child was discharged having gained the necessary weight. Our findings suggest that modification of the uterine artery waveform may occur independently of trophoblast invasion of the spiral arteries. Other theories that may explain the changes in the uterine artery waveform during pregnancy are discussed.Universidade de Taubaté (Unitau), Fac Med Sc

Methylenetetrahydrofolate reductase gene polymorphisms and their association with trisomy 21

Made available in DSpace on 2019-09-12T16:53:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2005Objectives To verify whether the frequencies of 5,10-methylenotetrahydrofolate reductase (MTHFR) polymorphisms at positions 677 and 1298 are higher in women with children affected by trisomy 21 than in those with chromosomally normal offspring. Methods A case-control study was carried out with 70 women whose children had trisomy 21 and 88 controls whose children were chromosomally normal. The frequencies of poly morph isms of points C677T and A1298C of MTHFR gene coding were studied in these two groups. Odds ratios (OR) for having a child affected by trisomy 21 were estimated for homozygosis, heterozygosis or the absence of the above-mentioned MTHFR polymorphisms. Logistic regression models were used to control for the effect of confounding variables on these odds ratios. Results The frequency of joint heterozygotic polymorphism (677 and 1298) was significantly higher in women with children affected by trisomy 21 than in those with chromosomally normal offspring (OR: 5.7). Conclusions The presence of joint heterozygotic polymorphism in the codifying gene for MTHFR was a risk factor for having a child with trisomy 21. Copyright (C) 2005 John Wiley & Sons, Ltd.Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, BR-13081970 Campinas, SP, Brazil; Univ Estadual Campinas, Sch Med Sci, Dept Med Genet, BR-13081970 Campinas, SP, Brazil; Universidade de Taubaté (Unitau), Sch Med Sci, Dept Obstet & Gynecol; Univ Estadual Campinas, Sch Med Sci, Dept Obstet & Gynecol, BR-13081970 Campinas, SP, Brazi

Methylenetetrahydrofolate reductase gene polymorphisms and their association with trisomy 21

Objectives To verify whether the frequencies of 5,10-methylenotetrahydrofolate reductase (MTHFR) polymorphisms at positions 677 and 1298 are higher in women with children affected by trisomy 21 than in those with chromosomally normal offspring. Methods A case-control study was carried out with 70 women whose children had trisomy 21 and 88 controls whose children were chromosomally normal. The frequencies of poly morph isms of points C677T and A1298C of MTHFR gene coding were studied in these two groups. Odds ratios (OR) for having a child affected by trisomy 21 were estimated for homozygosis, heterozygosis or the absence of the above-mentioned MTHFR polymorphisms. Logistic regression models were used to control for the effect of confounding variables on these odds ratios. Results The frequency of joint heterozygotic polymorphism (677 and 1298) was significantly higher in women with children affected by trisomy 21 than in those with chromosomally normal offspring (OR: 5.7). Conclusions The presence of joint heterozygotic polymorphism in the codifying gene for MTHFR was a risk factor for having a child with trisomy 21. Copyright (C) 2005 John Wiley & Sons, Ltd.25131196119

Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.status: publishe

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Maternal gene polymorphisms involved in folate metabolism and risk of Down syndrome offspring: a meta-analysis

Studies investigating the association between gene polymorphisms involved in homocysteine/folate metabolism and Down syndrome (DS) have reported contradictory or inconclusive results. A meta-analysis of 11 case-control studies relating MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms to the maternal risk of DS was carried out. For MTHFR C677T polymorphism the heterogeneity between studies was significant (P = 0.03) and the random effects (RE) pooled odds ratio (OR) was not significant: RE OR = 1.18 (0.99-1.40). The recessive model for allele MTHFR 677T showed nonsignificant heterogeneity overall (P = 0.21) and the association was not significant: fixed effects (FE) OR = 1.27 (0.98-1.64). However, sensitivity analysis changed the pattern of results and the association became marginally significant [FE OR = 1.31 (1.01-1.71)]. The dominant model showed no association. Finally, statistically significant associations between the MTHFR A1298C and MTRR A66G gene polymorphisms and the risk of DS were not found. The cumulative meta-analysis of MTHFR C677T showed a trend toward an association as the amount of data increased, and the recursive cumulative meta-analysis indicated that there was insufficient evidence for claiming or denying an association for all gene polymorphisms. In addition, there was no difference between the magnitude of effect observed in large versus small studies. Large and rigorous case-control studies that investigate gene-gene and gene-environment interactions need to be performed before conclusive claims about the genetics of DS can be made