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Background and objective Routine antenatal anti-D prophylaxis (RAADP) to RhD-negative women is most often administered in gestational age (GA) 28-30 weeks with the next anti-D dose administered postpartum. The aim of this study was to analyse the proportion of RhD-negative women where RAADP is not detectable at term and in a pilot study to investigate whether RAADP administered in GA 28 and 38 results in detectable levels at term, post-term and post-delivery. Materials and methods In a retrospective analysis, 4280 RhD-negative women carrying an RHD positive fetus were included and the proportion with a negative antibody screen at delivery was determined. In the second part, 39 pregnancies were included prospectively, a second dose of RAADP was administered in GA 38 weeks, and anti-D was quantified before the second dose and then weekly for 5 weeks. Results In the retrospective analysis, 20·5% (856/4280) with RAADP administered in GA 28 were negative in routine antibody screening at delivery. In the small prospective study, 18% (7/39) had a negative antibody screen and 26% (10/39) had levels below 0·005 IU/ml, in the quantification assay, in GA 38. Anti-D prophylaxis administered in GA 38 showed detectable levels of anti-D up to 30 days post-delivery, with concentration at delivery 0·060 ± 0·034 IU/ml (mean ± SD). Conclusion Approximately 20% of the RhD-negative women show non-detectable levels of anti-D at term. A second dose of RAADP at GA 38 results in stable concentrations of anti-D at term, post-term and post-delivery, but with large interindividual variation.

Introduction: We present a review of all cases of intravascular transfusions in red cell alloimmunization over a time span of 20 years in Stockholm. The aim of the study is to compare our results with published results from larger centers and to identify areas that can be further improved. Material and Methods: A retrospective cohort study was conducted of all women treated with intrauterine transfusions due to erythrocyte immunization in our hospital between June 1990 and June 2010. Primary outcome variables were fetal and neonatal survival, procedure-related complications and gestational age at delivery. Results: A total of 284 intrauterine transfusions were performed in 84 pregnancies, with an overall survival rate of 91.8%. Procedure-related and fatal complications occurred in the present study in 4.9 and 1.4% of fetuses or neonates, respectively. Procedure-related complications were significantly more common in free-loop transfusions than in transfusions in the intrahepatic part of the umbilical vein (OR: 5.4, p = 0.025). There was no significant difference between the intrahepatic and the placental cord insertion route (p = 0.83). Gestational age at first transfusion was significantly associated with an increased risk of a procedure-related complication (OR: 0.8, p = 0.019). Of the live-born infants, 24% of the neonates were born before gestational week 34. Discussion: Our study confirms previous studies demonstrating favorable results with intravascular transfusions.

20 individuals working organic chemistry and 11 theologians (referents) from the same university were investigated for frequencies of micronuclei in cultured lymphocytes. The chemists had been exposed for 3 to 36 (mean 12) years. No effect of the chemical exposure was found on the micronucleus frequencies. The lack of effect may be due to the improvement of the work environment in chemical laboratories.

Objective The deck crew on tankers can be exposed to high concentrations of benzene and other chemicals during loading, unloading and tank-cleaning operations. The objective of this study was to investigate whether genotoxic or other early health effects of cargo vapour exposure could be detected in coastal tanker crews. Methods The association between exposure to cargo vapours and clinical symptoms and signs, spirometry, blood cell count, blood tests for liver function, and the frequency of micronuclei and sister chromatid exchanges in peripheral lymphocytes was studied in a cross-sectional investigation of 107 male crew members (66 deck crew and 41 others) on ten coastal tankers. Results Seven of the tankers had automatic cargo level gauging systems but some of the ships still had open hatches during loading and unloading operations. Acute symptoms such as headache, nausea, vertigo, fatigue and dizziness after loading or tank-cleaning operations were reported by 56 of the 66 deck crew members (85%). Irritation of the mucous membrane in eyes and upper respiratory tract by cargo vapours were also common in this group. Obstructive symptoms were more common in the group with the highest exposure to cargo vapours but persistent effects on lung function (vital capacity and forced expiratory volume in l s), nervous system, liver enzymes or blood counts were not found. The frequency of micronuclei after mitotic stimulation with phytohaemagglutinin was higher among the deck crew (mean 4.2, SEM 0.40) than in other crew members (mean 3.6, SEM 0.35), although the difference was not statistically significant. We found no association between exposure and the frequency of sister chromatid exchanges or micronuclei after stimulation with pokeweed mitogen. Conclusion This study indicates that exposure to cargo vapours in coastal tanker crews may cause symptoms in the respiratory and nervous systems.

Objective To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP). Materials and Methods We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy. Results During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500. Conclusions Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.

Objective To analyze the timing of Rhesus D (RhD) immunization in pregnancy and the consequences for the index pregnancy and for subsequent pregnancies to be able to optimize the design of antenatal screening and prevention programs. Design Retrospective cohort study. Setting Stockholm county, Sweden. Population All RhD immunized pregnant women 1990–2008 before the introduction of routine antenatal anti-D prophylaxis. Methods Data were collected from transfusion medicine registers and databases, medical records, the Swedish Medical Birth Register and the National Perinatal Quality Register and entered into a standardized database before analysis. Main outcome measures The order of pregnancy and trimester when immunization occurred and treatment of hemolytic disease of the fetus and newborn. Results A total of 290 RhD immunized women were included in the study. In 147/290 (51%) of the women, sensitization occurred with their first-born child and in 96/290 (33%) it occurred with their second-born child. Anti-D antibodies developed during the second or third trimester in 212/290 (73%) and in 61/290 (21%) at term or after delivery. In subsequent pregnancies 56% (144/259) of the neonates required treatment for hemolytic disease of the fetus and newborn. Conclusions Based on our study, at least half of the cases could potentially have been avoided by routine antenatal anti-D prophylaxis in the beginning of the third trimester. To optimize the beneficial effects of new prevention programs, we propose providing anti-D prophylaxis in gestational week 28–30 selectively to all RhD-negative women with RhD-positive fetuses.

OBJECTIVE: To develop a simple and robust assay suitable for fetal RHD screening in first-trimester pregnancy and to estimate the sensitivity and specificity of the test after its implementation in an unselected pregnant population. METHODS: Pregnant women attending their first antenatal visit were included, and fetal RHD determination was performed for all women who typed RhD-negative by routine serology. DNA was extracted by an automated system and quantitative polymerase chain reaction was done by an assay based on exon 4. Reporting criteria were simple and strict. RESULTS: Four thousand one hundred eighteen pregnancies, with a median gestational age of 10 weeks, were included. After 211 (5.1%) reanalyses, fetal RHD was reported positive in 2,401 (58.3%), negative in 1,552 (37.7%), and inconclusive in 165 (4.0%) based on the first sample. After a second sample in 147 of 165, only 14 remained inconclusive, all resulting from a weak or silent maternal RHD gene. Using blood group serology of the newborns as the gold standard, the false-negative rate was 55 of 2,297 (2.4%) and the false-positive rate was 15 of 1,355 (1.1%). After exclusion of samples obtained before gestational week 8, the false-negative rate was 23 of 2,073 (1.1%) and the false-positive rate was 14 of 1,218 (1.1%). Both sensitivity and specificity were close to 99% provided samples were not collected before gestational week 8. From gestational week 22, sensitivity was 100%. CONCLUSION: : Fetal RHD detection in early pregnancy using a single-exon assay in a routine clinical setting is feasible and accurate. LEVEL OF EVIDENCE: : I. (Less)

Occupational high-dose exposure to metallic mercury can cause immune disturbances in sensitive individuals. Whether low-dose exposure to inorganic mercury from dental amalgam has this effect in humans is one of the issues related to the concept of oral galvanism and is supported by results of animal studies. This study explored some cellular immune factors (B- and T-lymphocytes, T4, T8, monocytes, neutrophilic, eosinophilic, and basophilic granulocytes, and large unstained cells) and some humoral immune factors (immunoglobulins IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, albumin, alfa-1-antitrypsin, orosomucoid, haptoglobin, and antinuclear antibodies) in 41 healthy 15-y-old schoolchildren. The relationship between these factors and amalgam fillings and mercury concentrations in plasma (P-Hg) were investigated. A low, but significant correlation (r = 0.40, p.05) was found between the number of amalgam surfaces and the P-Hg values, which were low for both sexes (median value = 1.8 nmol/l). There was no significant influence of the number of amalgam surfaces or P-Hg on the immune factors tested, except random findings. The girls had significantly higher values of T8, IgG, and IgG1 than the boys.

Forty-five Swedish chimney sweeps and 49 controls were investigated with micronuclei stimulated by phytohemagglutinin and pokeweed mitogen and by analysis of lymphocyte subgroups and neutrophilic leukocytes. There was a statistically significant effect among sweeps with respect to both micronuclei variables and neutrophilic leukocytes. The effect on lymphocyte micronuclei was most prominent in pokeweed mitogen-stimulated cells, which may imply that the T4 lymphocytes were preferentially damaged by the occupational exposure.

Objective-To study the prevalence of Enterobius vermicularis and its association with finger sucking in young Swedish children.Design-Cross-sectional survey with a questionnaire for symptoms of infestation with Enterobius vermicularis, and the children's habit of finger sucking (including fingernail biting). Perianal tape-test for identification of eggs of Enterobius vermicularis.Setting-Primary care, day-care centres, and schools in a Swedish middle-sized town (approx. 80 000 inhabitants).Participants-172 children of both sexes, 4–10 years old.Main outcome measures-The prevalence of Enterobius vermicularis and its association with finger sucking.Results−21% of the children were symptom-free carriers of Enterobius vermicularis, and finger sucking was strongly associated with a positive tape-test (p=0.01).Conclusion-More children than previously known seemed to be symptom-free carriers of Enterobius vermicularis. Finger sucking should be considered when treating infested children and especially those with ...

Micronucleus frequencies and mitotic indices were analyzed in B, T4, and T8 lymphocytes from 40 smokers and 42 non-smoking referents. The highest level of micronuclei was found in T4 cells followed by T8 and B cells. These differences were statistically significant. There were statistically significant linear correlations between the micronucleus frequencies of all three subsets. There was a statistically significant effect of smoking only in the T8 cells. Smoking also increased the number of neutrophilic granulocytes and lymphocytes in the peripheral blood. There was a statistically significant effect of age on the micronucleus frequencies in T4 and T8 lymphocytes. The mitotic indices did not have any effect on the micronucleus frequencies and they were not influenced by smoking, age or sex.

Micronuclei were induced in human lymphocytes by mitomycin C or gamma radiation. After the incubation the cells were separated in B- and T-cells by an immunomagnetic method, i.e., Dynabeads. The cultures were stimulated by PHA. The effect of different incubation times (60-110 h) as well as different doses of mitomycin C (0-100 nmol/l) and gamma radiation (0-2 Gy) at an incubation time of 72 h were studied. There were significantly higher frequencies of micronuclei in B- than in T-cells, when micronuclei were induced by mitomycin C. This was not found with gamma radiation, probably because of a cytotoxic effect of this agent on the B-cells.

For 26 chloralkali workers exposed to inorganic mercury and 26 age-matched, occupationally unexposed referents, the frequency and size distribution of micronuclei were determined in peripheral lymphocytes stimulated with either phytohemagglutinin or pokeweed mitogen. For the exposed workers the mean concentrations of mercury in urine, plasma, and erythrocytes were 16 nmol/mmol of creatinine, 48 nmol/l, and 78 nmol/l, respectively, and their mean exposure time was 10 years. Neither the frequency nor the size of micronuclei was significantly different in the two groups; nor were there any correlations to current mercury levels. However, in the exposed group, and with phytohemagglutinin as the mitogen, a statistically significant correlation between previous exposure to mercury (cumulative exposure or number of blood mercury peaks) and the frequency of micronuclei was found. This association was also present when the effects of age and smoking were allowed for, and it may indicate an accumulation of cytogenetic effects in T-lymphocytes.

Fifteen gasoline pump mechanics and 15 controls were investigated with the lymphocyte micronucleus assay and also with differential count of leukocytes in the peripheral blood. The lymphocytes were stimulated with phytohemagglutinin and pokeweed mitogen in parallel cultures. The pump mechanics had increased frequencies and sizes of micronuclei in the pokeweed mitogen-stimulated cultures but not in those stimulated with phytohemagglutinin. The difference in effect between the 2 mitogens is probably due to an increased sensitivity of the B-lymphocytes to mutagens. The leukocyte count was significantly higher in the gasoline-exposed group. The effect of the occupational exposure was probably caused by the benzene content of the gasoline. The time-weighted average for 8 h was around 1 mg/m3 of benzene, but there were peak levels of 20 mg/m3.

Thirty-two male individuals exposed to isocyanates and amines during the production of plastic foams and 20 male referents were studied by cytogenetic methods (chromosomal aberrations, sister chromatid exchanges and micronuclei in lymphocytes) and by urinary mutagenic assays (thioether concentrations and mutagenic activity with Salmonella TA98 and E. Coli WP2 uvrA). The occupational exposure was monitored by measurements of toluene diisocyanate and N-methylmorpholine in work-room air. The levels were below the current Swedish hygienic standards. Although all parameters, except the sister chromatid exchanges, showed increased mean values for the exposed group compared to the referents, only the urinary thioether concentrations differed significantly. The study was, however, non-conclusive with regard to a genetic effect of the occupational exposure as measured by the cytogenetic parameters. This may be due to the low exposure level. In the micronuclei frequencies there was a significant effect of age. Smoking significantly affected the SCE frequencies, the thioether concentrations and the mutagenic activities in the Salmonella assay. There were statistically significant correlations between the urine specimens collected during one working day and the following morning with regard to the mutagenic activities in the Salmonella and E. coli assays, and in the thioether concentrations as well. The association between the different cytogenetic and urinary mutagenic assays were weak but there were several statistically significant correlation coefficients, indicating that the variables may have a common metabolic background.

For 20 glass-reinforced plastics workers exposed to styrene and 22 unexposed referents, the frequency and size distribution of micronuclei were determined for lymphocytes stimulated with phytohemagglutinin or pokeweed mitogen, and white blood cell counts were made. Furthermore, chromosome aberrations were scored for 11 of the exposed subjects and 15 of the referents. The mean level of styrene in the breathing zone of the workers was 56 mg/m3. Workers exposed to styrene did not show an increase in any of the cytogenetic end points studied when the effect of age and smoking was allowed for in a multiple regression analysis. A significant 30% increase in the number of peripheral monocytes was observed for the exposed workers. No correlations between the cytogenetic and hematological tests on one hand and the length of exposure time on the other could be detected.

Micronuclei were induced in vitro in human lymphocytes by mitomycin C, X-rays, vincristine, and colcemid and analyzed in cells with preserved cytoplasm. The micronucleus/cell nucleus ratio was measured. It was found that micronuclei induced by mitomycin C and X-rays were significantly smaller than those formed by vincristine and colcemid. Thus, in spite of the wide size span of human chromosomes, it could be shown that it is possible to differentiate between micronuclei formed by spindle-damaging agents (vincristine and colcemid) and those induced by agents directly damaging the chromosomes (mitomycin C and X-rays). Mitomycin C-induced micronuclei were smaller than those induced by X-rays, probably because the former agent preferentially produces chromatid fragments and the latter chromosome fragments.

Eighteen individuals exposed to lead in their work with repair and reconditioning of car radiators were investigated regarding blood lead levels and frequencies of lymphocyte micronuclei. The micronuclei werc analyzed in cells with preserved cytoplasm. The lead-exposed group was compared with 12 white-collar workers with no occupational lead exposure. The mean blood lead levels were 2.3 (range 1.50-3.30) and 0.42 (range 0.20-1.05) Kmolil, respectively, with no overlapping of exposed subjects and controls. There was no effect of lead exposure when the influences of age, smoking and drug intake were allowed for in a multivariate analysis. On the other hand, there was a striking effect of age on the frequency of micronuclei.