Associations between epigenetic aging and childhood peer victimization, depression, and suicidal ideation in adolescence and adulthood: A study of two population-based samples.

Background: Prior studies indicate that peer victimization (including bullying) is associated with higher risk for depression and suicidal ideation across the life course. However, molecular mechanisms underlying these associations remain unclear. This two-cohort study proposes to test whether epigenetic aging and pace of aging, as well as a DNA methylation marker of responsive to glucocorticoids, are associated to childhood peer victimization and later depressive symptoms, or suicidal ideation. Methods: Cohort 1: Epigenome-wide DNA methylation (EPIC array) was measured in saliva collected when participants were 10.47 years (standard deviation = 0.35) in a subsample of the Quebec Longitudinal Study of Child Development (QLSCD, n = 149 participants), with self-reported peer victimization at 6-8 years, depressive symptoms (mean symptoms, and dichotomized top 30% symptoms) and suicidal ideation at 15-17 years. Cohort 2: Epigenome-wide DNA methylation (EPIC array) was measured in blood collected from participants aged 45.13 years (standard deviation = 0.37) in a subsample of the 1958 British Birth cohort (1958BBC, n = 238 participants) with information on mother-reported peer victimization at 7-11 years, self-reported depressive symptoms at 50 years, and suicidal ideation at 45 years. Five epigenetic indices were derived: three indicators of epigenetic aging [Horvath's pan-tissue (Horvath1), Horvath's Skin-and-Blood (Horvath2), Pediatric-Buccal-Epigenetic age (PedBE)], pace of aging (DunedinPACE), and stress response reactivity (Epistress). Results: Peer victimization was not associated with the epigenetic indices in either cohort. In the QLSCD, higher PedBE epigenetic aging and a slower pace of aging as measured by DunedinPACE predicted higher depressive symptoms scores. In contrast, neither the Horvath1, or Horvath2 epigenetic age estimates, nor the Epistress score were associated with depressive symptoms in either cohort, and none of the epigenetic indices predicted suicidal ideation. Conclusion: The findings are consistent with epigenome-wide and candidate gene studies suggesting that these epigenetic indices did not relate to peer victimization, challenging the hypothesis that cumulative epigenetic aging indices could translate vulnerability to depressive symptoms and suicidal ideation following peer victimization. Since some indices of epigenetic aging and pace of aging signaled higher risk for depressive symptoms, future studies should pursue this investigation to further evaluate the robustness and generalization of these preliminary findings.

[Prevention of perinatal hepatitis B virus transmission. Epidemiology and cost/efficacy ratio in the Paris region]. / Prévention de la transmission périnatale du virus de l'hépatite B. Epidémiologie et rapport coût/efficacité dans la région de Paris.

The HBs antigen (AgHBs) was detected in 152 out of 6605 (2.3 percent) pregnant women who attended four representative maternity clinics in the Paris region. In 98 percent of the cases this finding reflected chronic hepatitis B virus infection. Among women born outside France (47 percent of the women tested, 79 percent of the AgHBs positive women), the relative risk was 6 for Asiatics, 5.5 for Africans and 4 for French women born in overseas departments or territories. Whatever the women's geographical origin, studies of their medical history revealed no significant difference between AgHBs positivity and AgHBs negativity. Overcrowding and multiparity correlated globally with the presence of AgHBs, but this correlation was absent in French women born in France. In non-African and non-Asiatic women detection guided by medical and socio-familial criteria would not be efficacious. The authors recommend systematic detection of AgHBs in pregnant women and estimate at about 180,000 french francs the cost of prevention for each case evolving toward the vital complications of chronic hepatitis B virus infection, an outcome which in the long term may affect 600 individuals born each year and who had contracted the infection during the perinatal period.

Fetal lactic dehydrogenase variation in normal pregnancy and in cases of severe intra-uterine growth restriction.

Physiological and pathological fetal levels of lactic dehydrogenase (LDH), including its five different iso-enzymes are still poorly known. Our objectives were to compare total LDH levels and its five iso-enzymes between a control group of healthy fetuses and a group of fetuses with severe intra-uterine growth restriction (IUGR), and to determine the biochemical associations and the prognostic value of elevated LDH activity in fetuses with IUGR. Total LDH levels, haematologic values and liver enzyme activities were measured in 108 healthy fetuses from 17 to 37 weeks of gestation and in 44 fetuses with severe IUGR. Total fetal LDH in plasma from the healthy fetuses were constant throughout pregnancy (mean (SD)= 305.09 (46.97)). Total LDH values in plasma significantly increased in cases of IUGR (p=0.003), and the degree of increase was significantly correlated with fetal erythroblastosis (n =44, r=0.80, p<0.001). LDH 5 significantly decreased in the IUGR group (p=0.03). Total LDH values strictly above 400 IU/l (a value equal to the mean+2 SD in the healthy fetus group) were found to be significantly associated with thrombocytopenia (p<0.001), erythroblastosis (p=0.008) and an increase in AST value (p=0.03). These results suggest that the fetal LDH value in plasma is a useful biological marker for severe chronic distress.

[The perinatal transmission of the hepatitis B virus in the Paris area]. / Transmission périnatale du virus de l'hépatite B dans la région de Paris.

HBsAg was detected in 152 pregnant women among 6,605 (2.3%) screened in the prenatal clinics of four hospitals representative of the Paris metropolitan area. In 98% of cases, HBsAg positivity indicated chronic HBV carrier status. Among patients born out of continental France (47% of screened women, 79% of positive women) relative risk of chronic infection was 6 in Asians, 5.5 in Africans, and 4 in French women born in non-continental France. No significant difference in medical history was seen between HBsAg-positive and HBsAg-negative patients, in any of the birthplace groups. In women born out of continental France, number of children and crowding in the home were correlated with HBsAg-positivity; these correlations were not found in French women born in continental France. In non-African, non-Asian women, screening on the basis of medical, social and familial criteria (simulated in this study) would not be effective. Routine screening for HBsAg in pregnancy is advocated. The cost of the prevention of each case of perinatally acquired chronic HBV infection by routine screening followed by prophylactic treatment of a risk neonates was estimated at 180,000 French Francs (35,000 dollars). This approach is the only means of preventing the long-term life-threatening complications of chronic HBV infection in the 600 neonates born each year in France to HBsAg-positive mothers.

[Perinatal transmission of the hepatitis B virus in Paris region]. / Transmission périnatale du virus de l'hépatite B dans la région de Paris.

HBsAg was detected in 152 pregnant women among 6,605 (2.3%) screened in the prenatal clinics of four hospitals representative of the Paris metropolitan area. In 98% of cases, HBsAg positivity indicated chronic HBV carrier status. Among patients born out of continental France (47% of screened women, 79% of positive women) relative risk of chronic infection was 6 in Asians, 5.5 in Africans, and 4 in French women born in non-continental France. No significant difference in medical history was seen between HBsAg-positive and HBsAg-negative patients, in any of the birthplace groups. In women born out of continental France, number of children and crowding of the home were correlated with HBsAg-positivity; these correlations were not found in French women born in continental France. In non-African, non-Asian women, screening on the basis of medical, social and familial criteria (simulated in this study) would not be effective. Routine screening for HBsAg in pregnancy is advocated. The cost of the prevention of each case of perinatally acquired chronic HBV infection by routine screening followed by prophylactic treatment of at risk neonates was estimated at 180,000 French Francs (35,000 dollars). This approach is the only means of preventing the long-term life-threatening complications of chronic HBV infection in the 600 neonates born each year in France to HBsAg-positive mothers.

Two hundred intrauterine exchange transfusions in severe blood incompatibilities.

Two hundred intrauterine exchange transfusions were performed under local anesthesia in 107 cases of blood incompatibilities (60 fetuses with severe anemia and 47 with hydrops). Under sonographic guidance, depending on fetal and placental position, an optimal puncturing site was selected along the umbilical vein: placental insertion, fetal insertion, or fetal intraabdominal segment. Tests were immediately performed to confirm fetal origin of blood obtained and estimate hemoglobin level. Blood used for exchange transfusion was compatible with maternal blood and had a hematocrit value of 75%. Exchange transfusion was continued until a hemoglobin level of 16 gm/dl was reached. This procedure was first associated with intraperitoneal transfusions and was subsequently used independently once a month to maintain an adequate hemoglobin level. In 4 fetuses with hydrops, antenatal regression of this sign was observed in 33 cases (70.2%). Overall outcome of 107 fetuses after exchanges was 84 living neonates (78.5%), 15 deaths in utero, and eight neonatal deaths. The survival rate was 91.6% for fetuses without hydrops and 61.7% for those with hydrops. The advantage of exchange transfusion appears to be rapid and efficient correction of anemia with elimination of incompatible fetal red blood cells.