Erratum: Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study.

[This corrects the article DOI: 10.1093/eep/dvz023.][This corrects the article DOI: 10.1093/eep/dvz023.].

Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study.

Epidemiological studies suggest that father's smoking might influence their future children's health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers' smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11-54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected P values: 0.0006-0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR) < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers' smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers' exposures might persistently modify their future offspring's epigenome.

Monitoring and treatment of anti-D in pregnancy.

Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.

Effect of umbilical ring constriction on Wharton's jelly.

OBJECTIVE: The turgor of Wharton's jelly depends on osmotic and hydrostatic pressures. We tested the hypothesis that umbilical ring constriction has an impact on umbilical venous hemodynamics and thus on the volume of Wharton's jelly. METHODS: In a cross-sectional study of 237 low-risk singleton pregnancies, the cross-sectional area of the fetal end of the umbilical cord was determined using sonography at 20-41 weeks of gestation. The inner area of the two arteries and the vein was also measured and subtracted from the cord area to calculate the area of Wharton's jelly. Based on the Bernoulli equation, the degree of vein constriction at the umbilical ring was assessed using the blood velocity increment at the abdominal inlet. Regression analysis and SD-score statistics were used to construct mean values and to assess the effects. The dataset was also analyzed for gender-specific effects. RESULTS: The umbilical cord cross-sectional area increased with gestational age during the period 20-31 weeks, remaining essentially stable thereafter. The Wharton's jelly increased with gestational age from 20 until 31-32 weeks of gestation and remained at the same level for the rest of the pregnancy. At mid-gestation, on average 70% of the cord cross-sectional area was occupied by Wharton's jelly; at 31 weeks and later this value was 60%. Umbilical vein constriction was associated with reduced umbilical cord cross-sectional area and Wharton's jelly in female fetuses (P = 0.0007 and P = 0.003, respectively), but not in male fetuses. CONCLUSIONS: Under physiological conditions, umbilical ring constriction affects umbilical vein hemodynamics, with corresponding effects on the umbilical cord cross-sectional area and the amount of Wharton's jelly. Interestingly, the effects are gender-specific.

The effect of vascular constriction on umbilical venous pulsation.

OBJECTIVES: Umbilical venous pulsation is an important sign of hemodynamic compromise, but is also found under normal physiological conditions. Mathematical modeling suggests that vascular compliance is a determinant for pulsation, and we tested this by studying velocity pulsation at three sites on the umbilical vein. METHODS: In a cross-sectional study of 279 low-risk pregnancies (20-40 weeks' gestational age) blood flow velocity in the umbilical vein was determined before, within and after the umbilical ring in the fetal abdominal wall, and the incidence and magnitude of pulsation (the difference between the maximum and minimum velocity during a pulse, and pulsatility index) were noted. Based on the fact that the vessel cross-sectional area is an important determinant of compliance, we measured the diameter and time-averaged maximum velocity to reflect variation in diameter and compliance at the three sites. RESULTS: The incidence of umbilical venous pulsation was higher at the umbilical ring in the abdominal wall (242/279, 87%, 95% CI 82-90) than in the cord (43/198, 22%, 95%CI 16-27) or intra-abdominally (84/277, 30%, 95% CI 25-36) (P < 0.001). When pulsation was observed intra-abdominally, the pulsatility was not different from that at the umbilical ring (P = 0.16). However, the lowest pulsatility was found in the cord vein (P < 0.0001), where the largest vein diameter was found. CONCLUSION: The high incidence of venous pulsation at the umbilical ring where diameter and compliance are low supports the suggestion that local compliance is an important factor influencing pulsation in fetal veins.

The development of high venous velocity at the fetal umbilical ring during gestational weeks 11-19.

OBJECTIVE: To determine the occurrence of high venous velocities at the umbilical ring in the normal early second trimester, based on the assumption that a narrow umbilical ring may cause obstruction and increased venous blood velocity at the abdominal wall. DESIGN: Cross-sectional study. SETTING: Hospital antenatal clinic. POPULATION: One hundred and one low risk singleton pregnancies specifically recruited for the study. METHODS: Ultrasound was used at 11-19 weeks to determine the diameter and velocity in the umbilical vein at the fetal end of the cord and at the inlet through the abdominal wall. Outcome measures 10th, 50th and 90th centiles were estimated for the time-averaged maximum velocity in the cord and at the abdominal inlet. The increase of velocity as the blood entered the abdominal wall was calculated in percent of the velocity in the cord. RESULTS: During weeks 11-12 there was hardly any difference between blood velocity in the umbilical vein at the umbilical ring and that in the cord. From week 13 onwards it was increasingly common to find blood acceleration at the umbilical ring of 50-500%. Velocity increment >50% was found in 0/12 fetuses (0%) at 11-12 weeks, 5/20 (25%) at 13-14 weeks, and in 21/28 (75%) at 17-19 weeks. CONCLUSIONS: Blood velocity is higher in the umbilical vein at the abdominal wall than the cord, particularly after 13 weeks of gestation. If acceleration of blood velocity at the umbilical ring is a sign of a narrow inlet, it seems that a progressive tightening occurs during the second trimester.

Retinal detachment in association with preeclampsia and abruptio placentae.

Retinal detachment is a rare complication of preeclampsia, eclampsia and abruptio placentae. We report a case of bilateral retinal detachment in association with severe preeclampsia complicated with abruptio placentae, intrauterine fetal death and disseminated intravascular coagulation. In obstetric complications, placental thromboplastin may release into maternal circulation and activate the extrinsic coagulation system with resultant disseminated intravascular coagulation. This may be responsible for choroidal ischemia and consequent serous retinal detachment.