Ove Axelsson

Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta

Background. Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues such as bone, cartilage, and adipose. Adult human leukocyte antigen (HLA)-matched MSC have been used in cellular therapies of bone disorders such as osteogenesis imperfecta, with promising results. Methods. A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesis imperfecta, underwent transplantation with allogeneic HLA-mismatched male fetal MSC in the 32nd week of gestation. Engraftment analyses of donor cells, immunologic reaction against donor cells, and the well-being of the patient were assessed. Results. At 9 months of age, on slides stained for osteocalcin or osteopontin, a centromeric XY-specific probe revealed 0.3% of XY-positive cells in a bone biopsy specimen. Whole Y genome fluorescent in situ hybridization staining showed a median of 7.4% Y-positive cells (range, 6.8%–16.6%). Bone histology showed regularly arranged and configurated bone trabeculae. Patient lymphocyte proliferation against donor MSC was not observed in co-culture experiments performed in vitro after MSC injection. Complementary bisphosphonate treatment was begun at 4 months. During the first 2 years of life, three fractures were noted. At 2 years of corrected age, psychomotor development was normal and growth followed the same channel, −5 SD. Conclusions. The authors’ findings show that allogeneic fetal MSC can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.

Preterm and term births of small for gestational age infants: a population‐based study of risk factors among nulliparous women

Objective To study risk factors for small for gestational age (SGA) infants by gestational age among nulliparous women and to estimate mortality rates among SGA and appropriate‐for‐gestational‐age (AGA) infants by gestational age.

Water-gymnastics reduced the intensity of back/low back pain in pregnant women

OBJECTIVE To investigate if water-gymnastics during pregnancy may reduce the intensity of back/low back pain and the number of days on sick-leave. METHODS A prospective, randomized study. One hundred and twenty-nine women were randomized to participate in water-gymnastics once a week during the second half of pregnancy and 129 were randomized to a control group. The women in both groups filled in questionnaires in gestational weeks 18, 34 and within the first postpartum week. Every day from week 18 to labor they assessed the intensity of back/low back pain. RESULTS Back pain intensity increased during pregnancy. No excess risk for the pregnancy associated with water-gymnastics was observed. The women participating in water-gymnastics recorded a lower intensity of back/low back pain. The total number of days on sick-leave because of back/low back pain was 982 in the water-gymnastics group (124 women) compared with 1484 in the control group (120 women). After weeks 32 33, seven women in the water-gymnastics group compared with 17 in the control group were on sickleave because of back/ low back pain (p=0.031). CONCLUSIONS Intensity of back/low back pain increased with advancing pregnancy. There was no excess risk for urinary or vaginal infections associated with water-gymnastics. Water-gymnastics during the second half of pregnancy significantly reduced the intensity of back/ low back pain. Water-gymnastics decreased the number of women on sick-leave because of back/low back pain. Water-gymnastics during pregnancy can be recommended as a method to relieve back pain and may reduce the need for sick-leave.

Comparison of umbilical-artery velocimetry and cardiotocography for surveillance of small-for-gestational-age fetuses

Intrauterine growth retardation is associated with an increased risk of fetal asphyxia as well as greater perinatal morbidity and mortality. Ultrasound fetometry enables detection of fetuses that are small for gestational age. Doppler velocimetry of the umbilical artery has good predictive ability for fetal distress, but it is not yet clear whether it could replace cardiotocography in antenatal surveillance of small-for-gestational-age fetuses. We have done a randomised comparison of the two methods. At four obstetric departments in Sweden, women with fetuses found to be small on ultrasound examination at 31 completed weeks of pregnancy or later were randomly assigned to antenatal surveillance with either doppler velocimetry (doppler; 214) or cardiotocography (CTG; 212). Pregnancies in the doppler group were managed according to a protocol based on blood-flow classes deriving from the semiquantitative evaluation of umbilical-artery velocity waveforms; unless the pregnancy was complicated by any other disorder, no antenatal cardiotocography was done. By comparison with the CTG group, the doppler group had fewer monitoring occasions (mean 4.1 [SD 3.1] vs 8.2 [6.2], p < 0.01), antenatal hospital admissions (68 [31.3%] vs 97 [45.8%], p < 0.01), inductions of labour (22 [10.3%] vs 46 [21.7%], p < 0.01), emergency caesarean sections for fetal distress (11 [5.1] vs 30 [14.2%], p < 0.01), and admissions to neonatal intensive care (76 [35.5%] vs 92 [43.4%], p = 0.10). The groups did not differ in gestational age at birth, birthweight, Apgar scores, or total number of caesarean deliveries. Umbilical-artery doppler velocimetry of small-for-gestational-age fetuses allows antenatal monitoring and obstetric interventions to be aimed more precisely than does cardiotocography.

Sinistrality—a side-effect of prenatal sonography: A comparative study of young men

Although ultrasound during pregnancy is used extensively, there is little published on adverse fetal effects. We undertook a cohort study including men born in Sweden from 1973 to 1978 who enrolled for military service. We estimated relative risks for being born left-handed according to ultrasound exposure in fetal life using logistic regression analysis. Eligible for the study were 6,858 men born at a hospital that included ultrasound scanning in standard antenatal care (exposed) and 172,537 men born in hospitals without ultrasound scanning programs (unexposed). During the introduction phase (1973 to 1975) there was no difference in left-handedness between ultrasound exposed and unexposed (odds ratio = 1.03, 95% confidence interval (CI) = 0.91 to 1.17). When ultrasonography was offered more widely (1976 to 1978), the risk of left-handedness was higher among those exposed to ultrasound compared with those unexposed (odds ratio = 1.32, 95% CI = 1.16 to 1.51). We conclude that ultrasound exposure in fetal life increases the risk of left-handedness in men, suggesting that prenatal ultrasound affects the fetal brain.

Reference values for clinical chemistry tests during normal pregnancy

Objective  Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values.

Outcomes of post-term births: the role of fetal growth restriction and malformations.

OBJECTIVE To evaluate the risks of adverse pregnancy outcomes among term and post-term small for gestational age (SGA) and appropriate for gestational age (AGA) births, before and after excluding infants with congenital malformations. METHODS We did a population-based study of 510,029 singleton term (37-41 completed weeks) and post-term (at or after 42 weeks) births recorded in the Swedish Birth Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the risks of stillbirth, infant death, convulsions, meconium aspiration, and Apgar score less than 4 at 5 minutes. RESULTS Among term births, 2.2% were SGA; among post-term births, 3.8% were SGA. Compared with term AGA births, term SGA births were at increased risk of stillbirth (OR 8.02; 95% CI 6.57, 9.80) and infant death (OR 7.57; 95% CI 6.39, 8.96). Among post-term SGA births, the ORs were 10.56 (95% CI 6.95, 16.05) for stillbirth and 5.00 (95% CI 3.04, 8.22) for infant death. When births with congenital malformations were excluded, the risk of infant death decreased considerably. Risks of convulsions and Apgar score less than 4 were higher in SGA than AGA infants. Post-term AGA infants had no significant increase in the risks of stillbirth or infant death but did have increased risks of convulsions, meconium aspiration, and Apgar score less than 4. CONCLUSION The increased risk of stillbirth in post-term pregnancies is partly explained by an increased rate of SGA infants. The increased risk of death among SGA infants is caused to a large extent by congenital malformations.

Routine ultrasound screening in pregnancy and the children's subsequent handedness.

OBJECTIVE To study a possible association between ultrasound screening in early pregnancy and altered cerebral dominance measured by the prevalence of non-right handedness among children, particularly boys. METHODS Follow-up of 8 to 9 year old children to women who participated in a randomised controlled trial on ultrasound screening during pregnancy in 1985-87. The children were followed up through a questionnaire sent to their mothers. The dominant hand of the child was assessed by eleven questions. The dominant foot by one question. RESULTS No differences were found in non-right handedness between children in the screening and non-screening group. In separate analyses on ultrasound exposure and non-right handedness among boys a significant difference was found (odds ratio 1.33; 95% confidence interval 1.02-1.74). CONCLUSION This study could not rule out a possible association between non-right handedness among boys and ultrasound exposure in early fetal life. The association was, however, confined to analyses comparing exposed and non-exposed boys and no associations were found when the comparisons were performed according to the randomised groups.

Reference values for α1-acid glycoprotein, α1-antitrypsin, albumin, haptoglobin, C-reactive protein, IgA, IgG and IgM during pregnancy

The objective of this study was to establish reference intervals and decision limits for the interpretation of the acute phase proteins α1‐acid glycoprotein (orosomucoid), α1‐antitrypsin, C‐reactive protein (CRP), haptoglobin and albumin, IgA, IgG and IgM during pregnancy by longitudinal sampling from 52 healthy women with normal pregnancies. Each woman was sampled in weeks 7–17; weeks 17–24; weeks 24–28; weeks 28–31; weeks 31–34; weeks 34–38 and predelivery (–14–0 days prior to delivery) and postpartum (>6 weeks after delivery). The 2.5th and 97.5th percentiles were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. Reference values for α1‐acid glycoprotein, α1‐antitrypsin, albumin, haptoglobin, CRP, IgA, IgG and IgM are reported. Most of these proteins changed during normal pregnancy, as a reflection of the major physiological and biochemical changes that occur in pregnancy. A laboratory test result from a pregnant woman should be compared with pregnancy‐specific reference intervals.

Changes in transferrin glycosylation during pregnancy may lead to false-positive carbohydrate-deficient transferrin (CDT) results in testing for riskful alcohol consumption

BACKGROUND An alcohol-induced change in serum transferrin glycosylation, termed carbohydrate-deficient transferrin (CDT), is widely used as a biomarker of heavy long-term drinking. This study examined the transferrin glycosylation profile and the risk for false-positive CDT results during pregnancy. METHODS Serum samples were collected from 24 healthy pregnant women starting in gestation week 9-21, throughout pregnancy, and 8 or more weeks after delivery. Altogether 171 sera (5-9 samples/person) were analysed. Transferrin glycoforms were quantified as a percentage of total transferrin, using an HPLC candidate reference method for CDT. RESULTS During pregnancy, the relative disialo-, pentasialo- and hexasialotransferrin levels increased gradually, whereas trisialo- and tetrasialotransferrin were reduced. This effect was most pronounced in the third trimester. For disialotransferrin, the main target in CDT testing, initial values of 1.07 ± 0.17% (mean ± SD) increased to 1.61 ± 0.23% before delivery (~50% increase). Nine (38%) pregnant women reached %disialotransferrin values ≥ 1.7% (97.5th percentile for controls) but all results were < 2.0%. In the postpartum samples, all glycoform levels had returned towards the starting values. CONCLUSIONS These results suggest that the cutoff for %disialotransferrin and %CDT employed to indicate heavy long-term drinking need to be raised slightly in pregnant women, to minimize the risk for false-positive results on CDT testing.