Maternal Methyl-Group Donor Intake and Global DNA (Hydroxy)Methylation before and during Pregnancy.

It is still unclear to which extent methyl-group intake during pregnancy can affect maternal global DNA (hydroxyl)methylation. Pregnancy methylation profiling and its link with methyl-group intake in a healthy population could enhance our understanding of the development of pregnancy related disorders. One hundred forty-eight women were enrolled in the MANOE (MAternal Nutrition and Offspring's Epigenome) study. Thiry-four women were enrolled before pregnancy and 116 during the first trimester of pregnancy. Global DNA (hydroxy)methylation in blood using LC-MS/MS and dietary methyl-group intake (methionine, folate, betaine, and choline) using a food-frequency questionnaire were estimated pre-pregnancy, during each trimester, and at delivery. Global DNA (hydroxy)methylation levels were highest pre-pregnancy and at weeks 18-22 of pregnancy. We observed a positive relation between folic acid and global DNA methylation (p = 0.04) and hydroxymethylation (p = 0.04). A high intake of methionine pre-pregnancy and in the first trimester showed lower (hydroxy)methylation percentage in weeks 11-13 and weeks 18-22, respectively. Choline and betaine intake in the first weeks was negatively associated with hydroxymethylation. Women with a high intake of these three methyl groups in the second and third trimester showed higher hyrdoxymethylation/methylation levels in the third trimester. To conclude, a time trend in DNA (hydroxy)methylation was found and women with higher methyl-group intake showed higher methylation in the third trimester, and not in earlier phases of pregnancy.

Predictors of oligoamenorrhea at 1-year follow-up in premenopausal women using a levonorgestrel-releasing intrauterine system.

OBJECTIVE: The study was conducted to identify predictors of oligoamenorrhea at 12 months in levonorgestrel-releasing intrauterine system (LNG-IUS) users. DESIGN: A 12-month observational study. SETTING: Gynecologic outpatient clinic in a large regional hospital in Flanders, Belgium. POPULATION OR SAMPLE: A total of 150 women who had made an informed decision to use a LNG-IUS either as a method of contraception or to manage menorrhagia. METHODS: All women were premenopausal and first-time users. The variables recorded prior to insertion on Days 1 to 5 of the menstrual cycle were age, parity, body mass index, indication for LNG-IUS use, prior contraceptive use, menstrual bleeding history, length of the uterine cavity, endometrial thickness, number of antral follicles, serum follicle-stimulating hormone, inhibin B and anti-Müllerian hormone. Menstrual bleeding pattern, patient satisfaction or wish to discontinue the method was noted at 3, 6 and 12 months of follow-up visits. MAIN OUTCOME MEASURES: Menstrual bleeding pattern (amenorrhea, oligomenorrhea, menorrhagia) at 12 months was taken as the primary outcome measurement. Patient satisfaction was followed as a secondary outcome. RESULTS: Oligoamenorrhea was associated with a high patient satisfaction. A bleeding period less than 5 days, absence of severe uterine bleeding at baseline, LNG-IUS use for contraception and oligoamenorrhea at 3 months were predictors of a favorable outcome at 12 months in a univariate analysis. The absence of severe bleeding prior to LNG-IUS insertion was the only clinically useful predictor of favorable outcome in the multivariate analysis (odds ratio 0.13, 95% confidence interval 0.02-0.66). CONCLUSIONS: Patient profiling as described is not helpful in counselling women for intentional LNG-IUS use, especially not if it is planned as a method of managing menorrhagia.

Nuchal translucency thickness measurements for fetal aneuploidy screening: Log NT-MoM or Delta-NT, performer-specific medians and ultrasound training.

OBJECTIVES: To evaluate in fetal aneuploidy screening the desirability of using Fetal Medicine Foundation (FMF) normal medians of nuchal translucency thickness (NT) measurements or performer-specific medians, and whether the NT measurements should be expressed as Delta-NT or Log NT-MoM values. SETTINGS: First trimester-combined screening programme in a low risk population in Flanders, Belgium (Algemeen Medisch Laboratorium, Antwerp). METHODS: Pregnancies unaffected by trisomy 21 (T21) were screened by FMF-trained or other ultrasonographers. Performer-specific NT medians were established for FMF-trained and other ultrasonographers. NCSS Statistical Software was used to establish probability plots for Log NT-MoM and Delta-NT values, relative to performer-specific references or to the FMF-reference. RESULTS: A total of 16,096 pregnancies were evaluated. Six FMF-trainees and five other ultrasonographers each performed between 83 and 658 NT measurements. For the FMF-trainees, FMF-specific NT-MoM medians were close to one at a crown-rump length (CRL) between 50 and 80 mm, whereas the population-specific NT-MoM medians of the other ultrasonographers were close to one at a CRL between 40 and 80 mm. Performer-specific Delta-NT values fitted a Gaussian distribution between the 5th and 90th percentiles, while for the Log NT-MoM values this was between the 10th and 95th percentiles. CONCLUSION: We conclude that (i) the use of screening would benefit from performer-specific NT-medians based on Log NT-MoM values; (ii) the use of Log NT-MoM values is marginally better than the use of delta-NT MoMs; and (iii) NT measurements are valid at about 10 weeks (crown-rump length 40-45 mm) as well as at 11-13 weeks.

Population screening for fetal trisomy 21: easy access to screening should be balanced against a uniform ultrasound protocol.

OBJECTIVES: To evaluate the performance of a first-trimester fetal aneuploidy screening program, with a documented underestimation of nuchal translucency thickness measurements (NT) compared to the Fetal Medicine Foundation (FMF) reference range. METHODS: We analysed the data of Algemeen Medisch Laboratorium (AML) in Antwerp, Belgium, on combined screening with pregnancy-associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin (FB-hCG) and NT. NT-multiples of the median (MoM), relative to the FMF reference range, were used for risk calculations. RESULTS: The proportion of first-trimester screening tests in the total of serum screening tests increased from 1.3% (125/9424) in 2000 to 53.1% (6577/12 377) in 2003. Only 11.4% (1514/13 267) of NT measurements were performed according to FMF criteria. The 80.8% (21/26) trisomy 21 (T21) detection rate (DR) at cut off 1:300 resulted from maternal serum screening. NT measurements did not add to this DR, but reduced the false-positive rate from 16.8% (2212/13181) to 8.6% (1130/13181). Only 23.8% (5/21) of T21 detections were by FMF trainees. CONCLUSION: Easy access to screening and maternal serum parameters accounted for the majority of T21 detections in our first-trimester combined screening program.

Single-step maternal serum screening for trisomy 21 in the era of combined or integrated screening.

Single-step maternal serum screening (MSS) in the first (1MSS) or second (2MSS) trimester at maternal age > or =35 years was evaluated in the North Belgian region Flanders, where difficulties are encountered in the general introduction of combined or integrated screening algorithms. The fetal aneuploidy screening database of General Medical Laboratory AML in Antwerp was searched for 2MSS tests between 1992 and 1999 (alpha-fetoprotein, beta-human chorionic gonadotropin (beta-HCG) and unconjugated estriol, cut-off 1:300) and for 1MSS tests between 1999 and 2003 (free beta-HCG and pregnancy-associated plasma protein A, cut-off 1:85). At > or =35 years, the detection rate for trisomy 21 (DR) was 93.8% (15/16) for 2MSS and the screen-positive rate (SPR) was 24.5% (504/2061). For 1MSS, these figures were 85.7% (6/7) and 17.7% (109/615) respectively. To detect one trisomy 21, missed by MSS at > or =35 years of age, an additional number of 1,557 and 506 primary invasive procedures would be needed for 2MMS and 1MSS respectively. We conclude that the performance of both single-step 1MSS and 2MSS at maternal age > or =35 years in Flanders is excellent, even without the combination with ultrasound parameters or integration of first and second trimester parameters. The simplicity of both methods allows to consider them valuable options for fetal aneuploidy screening at advanced maternal age, until high quality combined or integrated screening is accessible to all pregnant women in Belgium.

Screening for trisomy 21 in Flanders: a 10 years review of 40.490 pregnancies screened by maternal serum.

OBJECTIVE: To evaluate maternal serum screening for trisomy 21 (MSS) in Flanders between 1992 and 2002. STUDY DESIGN: Data of a large database on the results of MSS, nuchal translucency (NT) and pregnancy outcome were analysed retrospectively. RESULTS: Despite an excellent performance of second trimester MSS at a maternal age > or = 35 years (94.4% detection rate (DR) of trisomy 21 at a false positive rate (FPR) of 22.4%), the proportion of patients above 35 years of age in the study population was significantly lower than in the Flemish general pregnant population (5.5% versus 8.9%, P < 0.001). In the population screened by MSS and NT, the DR of second trimester MSS at a 5% FPR was 44.4%, which was lower than 66.6% in the population screened by MSS without NT. When nine trisomy 21-affected pregnancies were compared to 3265 normal pregnancies, the mean NT-MoM values were not significantly different (1.16 +/- 0.89 versus 1.00 +/- 0.46, P > 0.05). Both the findings comply to a sequential screening practice where second trimester MSS is only performed after a normal measurement of NT in the first trimester. CONCLUSION: In Flanders, the uptake of second trimester maternal serum screening is low in women aged 35 years or more. Its screening performance decreased after the introduction of sequential screening.