Tono Djuwantono1,2, Jenifer Kiem Aviani3, Wiryawan Permadi4, Tri Hanggono Achmad5,6, Danny Halim6. 1. Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, West Java, Indonesia. tono.djuwantono@unpad.ac.id. 2. Bandung Fertility Center, Limijati Mother and Child Hospital, Bandung, West Java, Indonesia. tono.djuwantono@unpad.ac.id. 3. Bandung Fertility Center, Limijati Mother and Child Hospital, Bandung, West Java, Indonesia. 4. Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, West Java, Indonesia. 5. Department of Basic Medical Science, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia. 6. Research Center for Medical Genetics, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia.
Abstract
BACKGROUND: Various techniques in assisted reproductive technology (ART) have been developed as solutions for specific infertility problems. It is important to gain consensual conclusions on the actual risks of neurodevelopmental disorders among children who are born from ART. This study aimed to quantify the relative risks of cerebral palsy, intellectual disability, autism spectrum disorder (ASD), and behavioral problems in children from different ART methods by using systematic review and meta-analysis. Healthcare providers could use the results of this study to suggest the suitable ART technique and plan optimum postnatal care. METHODS: Pubmed, Google Scholar, and Scopus databases were used to search for studies up to January 2020. Of the 181 screened full manuscripts, 17 studies (9.39%) fulfilled the selection criteria. Based on the Newcastle-Ottawa scale ratings, 7 studies were excluded, resulting in 10 studies that were eventually included in the meta-analyses. Mantel-Haenszel risk ratio model was used in the meta-analysis, and the results are described using forest plot with 95% confidence interval. Heterogeneity was assessed using the I2 value. RESULTS: Pooled evaluation of 10 studies showed that the risk of cerebral palsy in children from assisted reproductive technology (ART) is higher than children from natural conceptions (risk ratio [RR] 1.82, [1.41, 2.34]; P = 0.00001). Risk of intellectual disability (RR 1.46, [1.03, 2.08]; P = 0.03) and ASD (RR 1.49 [1.05, 2.11]; P = 0.03) are higher in intracytoplasmic sperm injection (ICSI) children compared to conventional in vitro fertilization (IVF) children. The differences in the risk of neurodevelopmental disorders in children born after frozen and fresh embryo transfers are not significant. Analysis on potential cofounder effects, including multiple birth, preterm birth, and low birth body weight highlight possibilities of significant correlation to the risks of neurodevelopmental disorders. CONCLUSIONS: Pooled estimates suggest that children born after ART are at higher risk of acquiring cerebral palsy. ICSI treatment causes higher risk of intellectual disability and ASD. These findings suggest the importance of the availability of intensive care unit at the time of delivery and long-term developmental evaluation particularly in children from ICSI.
BACKGROUND: Various techniques in assisted reproductive technology (ART) have been developed as solutions for specific infertility problems. It is important to gain consensual conclusions on the actual risks of neurodevelopmental disorders among children who are born from ART. This study aimed to quantify the relative risks of cerebral palsy, intellectual disability, autism spectrum disorder (ASD), and behavioral problems in children from different ART methods by using systematic review and meta-analysis. Healthcare providers could use the results of this study to suggest the suitable ART technique and plan optimum postnatal care. METHODS: Pubmed, Google Scholar, and Scopus databases were used to search for studies up to January 2020. Of the 181 screened full manuscripts, 17 studies (9.39%) fulfilled the selection criteria. Based on the Newcastle-Ottawa scale ratings, 7 studies were excluded, resulting in 10 studies that were eventually included in the meta-analyses. Mantel-Haenszel risk ratio model was used in the meta-analysis, and the results are described using forest plot with 95% confidence interval. Heterogeneity was assessed using the I2 value. RESULTS: Pooled evaluation of 10 studies showed that the risk of cerebral palsy in children from assisted reproductive technology (ART) is higher than children from natural conceptions (risk ratio [RR] 1.82, [1.41, 2.34]; P = 0.00001). Risk of intellectual disability (RR 1.46, [1.03, 2.08]; P = 0.03) and ASD (RR 1.49 [1.05, 2.11]; P = 0.03) are higher in intracytoplasmic sperm injection (ICSI) children compared to conventional in vitro fertilization (IVF) children. The differences in the risk of neurodevelopmental disorders in children born after frozen and fresh embryo transfers are not significant. Analysis on potential cofounder effects, including multiple birth, preterm birth, and low birth body weight highlight possibilities of significant correlation to the risks of neurodevelopmental disorders. CONCLUSIONS: Pooled estimates suggest that children born after ART are at higher risk of acquiring cerebral palsy. ICSI treatment causes higher risk of intellectual disability and ASD. These findings suggest the importance of the availability of intensive care unit at the time of delivery and long-term developmental evaluation particularly in children from ICSI.
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