Objective: The objective of this study is to assess the safety of vaginal delivery in VLBW singletons in the vertex presentation. Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for studies on mode of delivery and neonatal outcome in VLBW singletons in the vertex presentation. A total of 28 studies met our inclusion criteria. Results: Vaginal delivery was not associated with an increase in overall neonatal mortality compared with cesarean delivery (OR 0.87, 95% CI 0.72–1.04). Vaginal delivery was associated with a significant decrease in mortality for the 1250–1500 g birthweight category (OR 0.57, 95% CI 0.36–0.92), while an increase in mortality in the 500–750 g category was not significant (OR 1.5, 95% CI 0.86–2.61). Severe intraventricular hemorrhage (IVH) was not associated with mode of delivery (OR 1.05, 95% CI 0.85–1.29), but the only two high quality study that assessed IVH of all grades found an increase in risk for IVH in vaginal delivery (OR 1.33, 95% CI 1.16–1.51). Conclusions: Vaginal delivery does not appear to increase the risk for neonatal mortality. However, current available data on neonatal morbidity are limited. More high-quality studies are needed to assess the association between mode of delivery and neonatal morbidity.

Objective: The objective of this study is to assess the safety of vaginal delivery in VLBW singletons in the vertex presentation. Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for studies on mode of delivery and neonatal outcome in VLBW singletons in the vertex presentation. A total of 28 studies met our inclusion criteria. Results: Vaginal delivery was not associated with an increase in overall neonatal mortality compared with cesarean delivery (OR 0.87, 95% CI 0.72–1.04). Vaginal delivery was associated with a significant decrease in mortality for the 1250–1500 g birthweight category (OR 0.57, 95% CI 0.36–0.92), while an increase in mortality in the 500–750 g category was not significant (OR 1.5, 95% CI 0.86–2.61). Severe intraventricular hemorrhage (IVH) was not associated with mode of delivery (OR 1.05, 95% CI 0.85–1.29), but the only two high quality study that assessed IVH of all grades found an increase in risk for IVH in vaginal delivery (OR 1.33, 95% CI 1.16–1.51). Conclusions: Vaginal delivery does not appear to increase the risk for neonatal mortality. However, current available data on neonatal morbidity are limited. More high-quality studies are needed to assess the association between mode of delivery and neonatal morbidity.

Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N = 10) and control pregnancies (N = 8) using a genome-wide approach with the Illumina® Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.

Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N = 10) and control pregnancies (N = 8) using a genome-wide approach with the Illumina® Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.

Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N = 10) and control pregnancies (N = 8) using a genome-wide approach with the Illumina® Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.

Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N = 10) and control pregnancies (N = 8) using a genome-wide approach with the Illumina® Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.

Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N = 10) and control pregnancies (N = 8) using a genome-wide approach with the Illumina® Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.

ABSTRACTData linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N = 10) and control pregnancies (N = 8) using a genome-wide approach with the Illumina® Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the two groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from a stochastic increase in genome-wide DNA methylation in IVF pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART-associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.