Flow cytometric measurement of DNA S-phase in human bone marrow cells: correcting for peripheral blood contamination

Abstract: The relationship between bone marrow (BM) cells with S-phase DNA content and the amount of peripheral blood contamination estimated as percentage lymphocytes+monocytes (L+MO) present in BM samples has been investigated in a total of 136 BM aspirates and biopsy expellates from 35 hematologically healthy individuals. A significant negative correlation was demonstrated between total, erythroid and myeloid BM cells in S-phase and the percentage of L+MO in the aspirates (r = 0.84, 0.57 and 0.49, respectively; p<0.0001). Based on the equation of the slope of the regression line, a correction formula adjusting the measured value of BM cells in S-phase to varying amounts of L+MO percentage has been worked out for the total and erythroid BM cells. In contrast, highly proliferating myelomonocytic cells and CD34⁺ cells did not show any significant correlation between cells in S-phase and percentage L+MO, indicating that peripheral blood contamination of BM aspirates is not a problem regarding kinetic investigations of these cells. In conclusion, the described flow cytometric method of analysing BM aspirates estimates the degree of peripheral blood contamination, as well as make possible a correct estimation of the DNA synthesis of several BM populations. The method is especially applicable when frequent BM sampling is required.     

How do we best detect toxic effects of drugs taken during pregnancy? A EuroMap paper.

It is a major clinical and public health problem that there is no clear strategy as to how we best make use of information obtained when pregnant women take drugs. For this reason, some pregnant women are not treated as they should be and some are given drugs they should not use. We suggest a monitoring system that combines some of the available datasets in Europe. Using these sources as a starting point, one can develop a system that has sufficient power to detect even rare diseases like congenital malformations and sufficient diversity to detect several possible outcomes from spontaneous abortions to childhood disorders. We also suggest that case-crossover designs should be used in case-control monitoring systems that carry a high risk of recall bias. These considerations are based upon our results from a European Union-funded concerted action called EuroMaP (Medicine and Pregnancy).     

Men's body mass index and infertility

BACKGROUND: In men, excess weight may be linked with altered testosterone, estradiol levels, poor semen quality and infertility. We investigated whether higher BMI among men is associated with infertility and if so, to what extent that effect might be mediated by altered sexual function. METHODS: A retrospective cohort study of pregnancies from 1999 through 2005 based within the Norwegian Mother and Child Cohort Study (MoBa). Questionnaires assessed mother's and father's height and weight and time to pregnancy. Our sample comprises 26 303 planned pregnancies. Couples were considered infertile if they took >or=12 months to achieve pregnancy or received infertility treatment. RESULTS: After adjusting for the woman's BMI, coital frequency and the ages and smoking habits of both partners, the odds ratio for infertility was 1.20 for overweight men [BMI 25-29.9; 95% confidence interval (CI) = 1.04-1.38] and 1.36 for obese men (BMI 30-34.9; 95% CI = 1.13-1.63) relative to men with low-normal BMI (20.0-22.4). When BMI was divided into eight categories, there was a trend of increased infertility with increased male BMI. The effect of men's BMI was nearly identical when coital frequency was not included indicating that the effect is not mediated by sexual dysfunction in heavier men. CONCLUSIONS: This study adds further support that men with excess body weight are at increased risk of infertility. Values may be underestimated because the most severe cases, couples who do not conceive, are not included in this birth cohort. Research is needed to see if weight loss improves fertility for these men.     

Increased risk of placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in the same mother

BACKGROUND: The risk of placenta previa may be increased in pregnancies conceived by assisted reproduction technology (ART). Whether the increased risk is due to factors related to the reproductive technology, or associated with maternal factors, is not known. METHODS: In a nationwide population-based study, we included 845,384 pregnancies reported to the Medical Birth Registry of Norway between 1988 and 2002 and compared the risk of placenta previa in 7568 pregnancies conceived after assisted fertilization, with the risk in naturally conceived pregnancies. To study the influence of ART more directly, we compared the risk of placenta previa between consecutive pregnancies among 1349 women who had conceived both naturally and after assisted fertilization. Odds ratios (OR), adjusted for maternal age, parity, previous Caesarean section and time interval between pregnancies were estimated using logistic regression. RESULTS: There was a six-fold higher risk of placenta previa in singleton pregnancies conceived by assisted fertilization compared with naturally conceived pregnancies [adjusted OR 5.6, 95% confidence interval (CI) 4.4-7.0]. Among mothers who had conceived both naturally and after assisted fertilization, the risk of placenta previa was nearly three-fold higher in the pregnancy following assisted fertilization (adjusted OR 2.9, 95% CI 1.4-6.1), compared with that in the naturally conceived pregnancy. CONCLUSIONS: The use of ART is associated with an increased risk of placenta previa. Our findings suggest that the increased risk may be caused by factors related to the reproductive technology.     

Perinatal mortality and mother's marital status at birth in subsequent siblings

The effect of marital status on perinatal mortality is studied for births in Norway, 1967-1981, in terms of relative risk (RR) of unmarried vs. married mothers. The births were linked in units of sibships. At first birth, RR decreased from 1.86 in 1967-1971 to 1.32 in 1977-1981. At second birth the perinatal mortality varied greatly according to marital history with a RR of 2.03 when comparing sibships where mothers were unmarried at both pregnancies with mothers married at both pregnancies. Almost no excess risk was demonstrated for mothers that were married at second birth, but unmarried at first. These mothers appeared to have no excess risk even at the first birth in spite of being unmarried. The results suggest that marital status is still a risk factor to be considered, even in the Scandinavian countries where the marginal effect of marital status in recent years has been reported to be low. To an increasing extent, the high risk women, previously identified by marital status, are now hidden in a larger low risk group which apparently has more stable family relations, e.g. tending to be married at second birth.