Aug 13, 2025
Neurodevelopmental outcome in Monochorionic Pregnancies complicated with TTTS following in utero laser treatment. A Systematic Review of the Literature and Meta – analysis.
- Nikolaos Machairiotis1,
- Ioanna Zouganeli2
- 1Third Department of Obstetrics and Gynaecology, University General Hospital “Attikon,” Medical school, National and Kapodistrian University of Athens, 12462 Athens, Greece;
- 2Third Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, 7 National and Kapodistrian University of Athens, 124 62 Athens, Greece
Protocol Citation: Nikolaos Machairiotis, Ioanna Zouganeli 2025. Neurodevelopmental outcome in Monochorionic Pregnancies complicated with TTTS following in utero laser treatment. A Systematic Review of the Literature and Meta – analysis.. protocols.io https://dx.doi.org/10.17504/protocols.io.rm7vz9be8gx1/v1
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this protocol and it's working
Created: August 11, 2025
Last Modified: August 13, 2025
Protocol Integer ID: 224474
Keywords: Twin-to-Twin Transfusion syndrome, TTTS, Neurodevelopment, Fetoscopic Laser Surgery, FLS, term neurodevelopment outcome after fl, neurodevelopmental outcome, fetoscopic laser surgery, twin, utero laser treatment, term neurodevelopment outcome, transfusion syndrome, monochorionic pregnancy, children with quintero stage iv, amnioreduction
Abstract
TTTS also known as the Twin-To-Twin transfusion syndrome is a rare complication that only affects monochorionic pregnancies. Through the course of time and advancement of medicine, various therapeutic approaches have been utilized to treat the Twin-to-Twin transfusion syndrome. The two most common approaches offered to patients up to this day are the
fetoscopic laser surgery (FLS) and the amnioreduction (AR). To properly evaluate the result of the applied treatment, the long-term neurodevelopment outcome after FLS should be taken into consideration. The authors will perform a review of the existing literature of the last 20 years on the neurodevelopmental outcome of twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. Articles will be reviewed after searching through the biggest electronic medical libraries and the snowball procedure. Two authors will perform duplication removal, abstract screening and full-text article assessment. Communication, gross motor, fine motor, problem solving and personal / social skills will be assessed in children with Quintero stage IV during pregnancy.
Guidelines
Exclusion criteria
Alternative language publications, letters, older studies and omission of at least one inclusion criterion for the result set will classify a study as irrelevant and the authors will exclude them. All cell culture studies, case reports, animal studies, case series will be deemed irrelevant by the authors. For any studies with overlapping populations, the authors concluded that only one should be included, the most recent one.
Experimental workflow
The authors will identify the studies after querying 4 different electronic medical databases. Duplicates between the 4 result-sets will be removed. The titles of these papers will be reviewed and irrelevant articles will be excluded from the result-set. Two authors will screen the abstracts of the remaining articles to identify only studies that will be of interest to the subject of the review. After the unrelated will be excluded, the remaining articles will be then assessed for eligibility by reading their full content. The authors also will perform the snowball procedure to identify any potential studies of interest.
Data Extraction
Data extracted will include study characteristics, patient demographics, Quintero stage, treatment details, follow-up duration, and neurodevelopmental outcomes.
Data Synthesis and Meta-Analysis
Review Manager 5.4.1 will be used for meta-analysis. Odds ratios (OR) with 95% confidence intervals (CI) will be calculated. Heterogeneity will be assessed using the I2 statistic. P-values 0.05 will be considered statistically significant. Forest plots will be generated to illustrate associations between Quintero stage IV and specific neurodevelopmental domains.
Materials
Materials and Methods
The authors will conduct a search through 4 of the biggest medical databases, MEDLINE, PUBMED, EMBASE and GOOGLE SCHOLAR. These databases will be utilized in order to search for relevant articles and studies up to November 2023 that describe outcomes for twin-to-twin transfusion syndrome pregnancies that were treated with fetoscopic laser surgery (FLS).
In order to include studies for reviewing, the authors will ensure that all relevant studies were referring to data that indicated an appropriate diagnosis of Twin-to-Twin transfusion syndrome. The studies should also utilize standard criteria for treatment and the treatment should have been performed via fetoscopic laser surgery (FLS). The studies should have also included data for neurologic impairment and morbidity that were collected from these patients at birth and up to their 6th year of life.
Troubleshooting
Materials and Methods
The authors will conduct a search through 4 of the biggest medical databases, MEDLINE, PUBMED, EMBASE and GOOGLE SCHOLAR. These databases will be utilized in order to search for relevant articles and studies up to November 2023 that describe outcomes for twin-to-twin transfusion syndrome pregnancies that were treated with fetoscopic laser surgery (FLS). The authors decided to only include studies from the last 20 years since the advancement of technology would make older methodologies obsolete.
The following terms will be used for searching: “ttts syndrome”, “twin-to-twin transfusion syndrome”, “ttts”, “neurodevelopment”, “neurodevelopmental”, “neurodevelopmental outcome”, “ttts syndrome neurodevelopment”, “neurodevelopmental result”, “twin-to-twin syndrome laser treatment”, “twin-to-twin syndrome laser therapy”, “ttts laser treatment”, “ttts laser therapy”, “ttts neurodevelopment”, “ttts neurodevelopmental outcome”, “ttts laser surgery uterus”, “twin-to-twin syndrome laser surgery uterus”, “ttts fls”, “ttts fetoscopic laser surgery” and the query used (((ttts OR (ttts syndrome) OR (twin-to-twin transfusion syndrome)) AND ((laser OR (laser therapy) OR (laser treatment) OR (laser treatment uterus) OR (laser therapy uterus) OR fls OR (fetoscopic laser surgery))) AND (outcome OR result)). There will be no other restrictions that were applied to the search query and papers only written in English will be included.
Two authors independently will assess the results initially by reading the abstracts. For the remaining relevant results, the two authors will perform a read of the remaining papers and by applying the inclusion and exclusion criteria that were decided in the beginning of the study they will narrow down the result sample to the relevant studies that will be of interest. For any disagreements amongst authors, the decision will be taken by a third reviewer in order to reach consensus on inclusion or exclusion of a paper. Following the snowball procedure, the authors manually will search the remaining papers for relevant articles in an attempt to find other related papers via citation mining.
Inclusion criteria
In order to include studies for reviewing, the authors will ensure that all relevant studies were referring to data that indicated an appropriate diagnosis of Twin-to-Twin transfusion syndrome. The studies should also utilize standard criteria for treatment and the treatment should have been performed via fetoscopic laser surgery (FLS). The studies should have also included data for neurologic impairment and morbidity that were collected from these patients at birth and up to their 6th year of life.
Exclusion criteria
Alternative language publications, letters, older studies and omission of at least one inclusion criterion for the result set will classify a study as irrelevant and the authors will exclude them. All cell culture studies, case reports, animal studies, case series will be deemed irrelevant by the authors. For any studies with overlapping populations, the authors concluded that only one should be included, the most recent one.
Experimental workflow
The authors will identify the studies after querying 4 different electronic medical databases. Duplicates between the 4 result-sets will be removed. The titles of these papers will be reviewed and irrelevant articles will be excluded from the result-set. Two authors will screen the abstracts of the remaining articles to identify only studies that will be of interest to the subject of the review. After the unrelated will be excluded, the remaining articles will be then assessed for eligibility by reading their full content. The authors also will perform the snowball procedure to identify any potential studies of interest.
Data Extraction
Data extracted will include study characteristics, patient demographics, Quintero stage, treatment details, follow-up duration, and neurodevelopmental outcomes.
Data Synthesis and Meta-Analysis
Review Manager 5.4.1 will be used for meta-analysis. Odds ratios (OR) with 95% confidence intervals (CI) will be calculated. Heterogeneity will be assessed using the I2 statistic. P-values < 0.05 will be considered statistically significant. Forest plots will be generated to illustrate associations between Quintero stage IV and specific neurodevelopmental domains.
Ethics and Dissemination
No ethical approval will be required as this study is based on published literature. Findings will be disseminated via publication in a peer-reviewed journal and presentation at relevant conferences.
Conflicts of Interest & Funding
The authors declare no conflicts of interest. Funding: None.
Protocol references
References
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10. Hopkins Medicine. Fetal Interventions – Fetoscopic Laser Surgery. Available online: https://www.hopkinsmedicine.org/gynecology-obstetrics/specialty-areas/fetal-therapy/fetal-interventions-procedures/fetoscopic-laser-surgery (accessed on 20 May 2025).
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Acknowledgements
Conflicts of Interest Funding
The authors declare no conflicts of interest. Funding: None.