DNA methylation differences at birth after conception through ART

STUDY QUESTION: Is there a relation between ART and DNA methylation (DNAm) patterns in cord blood, including any differences between IVF and ICSI? SUMMARY ANSWER: DNAm at 19 CpGs was associated with conception via ART, with no difference found between IVF and ICSI. WHAT IS KNOWN ALREADY: Prior studies on either IVF or ICSI show conflicting outcomes, as both widespread effects on DNAm and highly localized associations have been reported. No study on both IVF and ICSI and genome-wide neonatal DNAm has been performed. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study comprising 87 infants conceived with IVF or ICSI and 70 conceived following medically unassisted conception. The requirement for inclusion in the study was an understanding of the Swedish language and exclusion was the use of donor gametes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were from the UppstART study, which was recruited from fertility and reproductive health clinics, and the Born into Life cohort, which is recruited from the larger LifeGene study. We measured DNAm from DNA extracted from cord blood collected at birth using a micro-array (450k array). Group differences in DNAm at individual CpG dinucleotides (CpGs) were determined using robust linear models and post-hoc Tukey's tests. MAIN RESULTS AND THE ROLE OF CHANCE: We found no association of ART conception with global methylation levels, imprinted loci and meta-stable epialleles. In contrast, we identify 19 CpGs at which DNAm was associated with being conceived via ART (effect estimates: 0.5-4.9%, PFDR < 0.05), but no difference was found between IVF and ICSI. The associated CpGs map to genes related to brain function/development or genes connected to the plethora of conditions linked to subfertility, but funct

Caesarean section and risk for endometriosis: a prospective cohort study of Swedish registries

Objective To investigate the association between caesarean section and later endometriosis. Design A prospective cohort study. Setting The Swedish Patient Register (PAR) and the Swedish Medical Birth Registry (MBR). Sample Women who were delivered in Sweden between 1986 and 2004. Methods Women with the diagnosis of endometriosis, defined as codes 617 (International Classification of Diseases, ninth revision, ICD-9) or N80 (ICD-10), were retrieved from the PAR. Obstetric outcome was assessed through linkage with the MBR. Out of 709090 women, 3110 were treated as inpatients with a first diagnosis of endometriosis after their first delivery. Women with a diagnosis of endometriosis before their first delivery were excluded. Cox analyses were performed to obtain hazard ratios for endometriosis and adjusted for maternal age at first delivery, body mass index, maternal smoking, and years of involuntary childlessness at study entry. Kaplan-Meier estimates were performed to calculate the risk according to time elapsed. Main outcome In-hospital diagnosis of endometriosis. Results The Cox analyses yielded a hazard ratio of 1.8 (95%CI 1.7-1.9) for endometriosis in women who had had a previous caesarean section compared with women with vaginal deliveries only. The risk of endometriosis increased over time: one additional case of endometriosis was found for every 325 women undergoing caesarean section within 10years. No increase in risk could be seen after two caesarean deliveries. The risk of caesarean scar endometrioma was 0.1%. Conclusion In addition to the recognised risk of scar endometrioma, we found an association between caesarean section and general pelvic endometriosis. Further studies are needed to confirm our findings

Indications for cesarean section on maternal request--guidelines for counseling and treatment.

AIM: The aim was to find scientific evidence and, based on this, to develop national medical guidelines in Sweden for cesarean section on mother's request. BACKGROUND: More than 17% of all births in Sweden in 2008 were cesarean sections, compared to 5% at the beginning of the 1970s. About 8% of the cesarean sections were performed at mother's request. The predominant reason for this preference is fear of childbirth. When deciding whether to perform an elective cesarean section, the obstetrician must emphasize the long- and short-term health consequences for the mother and her baby, as well as weigh the risks associated with the procedure itself against not performing the procedure. Clarification is needed to determine for which conditions it is appropriate to comply with the mother's request. MATERIALS AND METHOD: A literature review was conducted to identify factors that were relevant as an argument to meet the request for cesarean section on maternal request. The authors analyzed these factors individually to determine. FINDINGS: The guidelines suggest that it is appropriate to comply with a woman's request for cesarean section if the reason for her request is deemed sufficiently serious and if, after participating in a counseling program, the woman persists in her request for cesarean section. CONCLUSION: A request for cesarean section where no medical indication is present should not be met without considerations concerning the safety of the mother and her baby, while also weighing the risk of adverse outcomes for mother and baby

Prior placental bed disorders and later dementia: a retrospective Swedish register-based cohort study

Objective To investigate the association between a history of placental bed disorders and later dementia. Design Retrospective population-based cohort study. Setting Sweden. Sample All women giving birth in Sweden between 1973 and 1993 (1 128 709). Methods Women with and without placental bed disorders (hypertensive disorders of pregnancy including pre-eclampsia, fetal growth restriction, spontaneous preterm labour and birth, preterm premature rupture of membranes, abruptio placenta, late miscarriages) and other pregnancy complications were identified by means of the Swedish Medical Birth Register. International classification of disease was used. Data were linked to other National Registers. Participants were followed up until 2013. The Cox proportional hazards model was used to calculate hazard ratios for women with and without pregnancy complications and were adjusted for possible confounders. Main outcome measures Diagnosis of vascular dementia and non-vascular dementia. Results Adjusted for cardiovascular disease and socio-demographic factors, an increased risk of vascular dementia was shown in women with previous pregnancy-induced hypertension (Hazard ratio [HR] 1.88, 95% CI 1.32-2.69), pre-eclampsia (HR 1.63, 95% CI 1.23-2.16), spontaneous preterm labour and birth (HR 1.65, 95% CI 1.12-2.42) or preterm premature rupture of membranes (HR 1.60, 95% CI 1.08-2.37). No statistically significant increased risk was seen for other pregnancy complications or non-vascular dementia even though many of the point estimates indicated increased risks. Conclusions Women with placental bed disorders have a higher risk for vascular disease. Mechanisms behind the abnormal placentation remain elusive, although maternal constitutional factors, abnormal implantation as well as impaired angiogenesis have been suggested. Tweetable abstract Placental bed syndromes associated with vascular dementia even after adjusting for cardiovascular disease

Psychiatric illness in women requesting caesarean section

Objective To compare psychiatric in-and outpatient care during the 5 years before first delivery in primiparae delivered by caesarean section on maternal request with all other primiparae women who had given birth during the same time period. Design Prospective, population-based register study. Setting Sweden. Sample Women giving birth for the first time between 2002 and 2004 (n = 64 834). Methods Women giving birth by caesarean section on maternal request (n = 1009) were compared with all other women giving birth (n = 63 825). The exposure of interest was any psychiatric diagnosis according to the International Statistical Classification of Diseases and Related Health Problems (ninth revision, ICD-9, 290-319; tenth revision, ICD-10, F00-F99) in The Swedish national patient register during the 5 years before first delivery. Main outcome measures Psychiatric diagnoses and delivery data. Results The burden of psychiatric illnesses was significantly higher in women giving birth by caesarean section on maternal request (10 versus 3.5%, P less than 0.001). The most common diagnoses were ` Neurotic disorders, stress-related disorders and somatoform disorders (5.9%, aOR 3.1, 95% CI 1.1-2.9), and ` Mood disorders (3.4%, aOR 2.4, 95% CI 1.7-3.6). The adjusted odds ratio for caesarean section on maternal request was 2.5 (95% CI 2.0-3.2) for any psychiatric disorder. Women giving birth by caesarean section on maternal request were older, used tobacco more often, had a lower educational level, higher body mass index, were more often married, unemployed, and their parents were more often born outside of Scandinavia (P less than 0.05). Conclusions Women giving birth by caesarean section on maternal request more often have a severe psychiatric disease burden. This finding points to the need for psychological support for these women as well as the need to screen and treat psychiatric illness in pregnant women.Funding Agencies|County Council of Ostergotland, Sweden</p

Psychiatric illness in women requesting caesarean section

Objective To compare psychiatric in-and outpatient care during the 5 years before first delivery in primiparae delivered by caesarean section on maternal request with all other primiparae women who had given birth during the same time period. Design Prospective, population-based register study. Setting Sweden. Sample Women giving birth for the first time between 2002 and 2004 (n = 64 834). Methods Women giving birth by caesarean section on maternal request (n = 1009) were compared with all other women giving birth (n = 63 825). The exposure of interest was any psychiatric diagnosis according to the International Statistical Classification of Diseases and Related Health Problems (ninth revision, ICD-9, 290-319; tenth revision, ICD-10, F00-F99) in The Swedish national patient register during the 5 years before first delivery. Main outcome measures Psychiatric diagnoses and delivery data. Results The burden of psychiatric illnesses was significantly higher in women giving birth by caesarean section on maternal request (10 versus 3.5%, P less than 0.001). The most common diagnoses were ` Neurotic disorders, stress-related disorders and somatoform disorders (5.9%, aOR 3.1, 95% CI 1.1-2.9), and ` Mood disorders (3.4%, aOR 2.4, 95% CI 1.7-3.6). The adjusted odds ratio for caesarean section on maternal request was 2.5 (95% CI 2.0-3.2) for any psychiatric disorder. Women giving birth by caesarean section on maternal request were older, used tobacco more often, had a lower educational level, higher body mass index, were more often married, unemployed, and their parents were more often born outside of Scandinavia (P less than 0.05). Conclusions Women giving birth by caesarean section on maternal request more often have a severe psychiatric disease burden. This finding points to the need for psychological support for these women as well as the need to screen and treat psychiatric illness in pregnant women.Funding Agencies|County Council of Ostergotland, Sweden</p