Fragile X syndrome, a common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP) due to a mutation in the FMR1 gene. We investigated the differentiation of neural stem cells generated from the brains of fmr1-knockout (KO) mice and from postmortem tissue of a fragile X fetus. Mouse and human FMRP-deficient neurospheres generated more TuJ1-positive cells (3-fold and 5-fold, respectively) than the control neurospheres generated from normal mouse and human brains, and these cells showed morphological alterations with fewer and shorter neurites and a smaller cell body volume. The number of cells expressing glial fibrillary acidic protein and generated by these neurospheres was reduced because of increased apoptotic cell death. Furthermore, there was an increase in a population of cells with intense oscillatory Ca 2؉ responses to neurotransmitters in differentiated cells lacking FMRP. In addition, the number of cells in a cohort of bromodeoxyuridine-labeled newborn cells was increased in the subventricular zone of the telencephalon of the fmr1-KO mouse in vivo. These results demonstrate substantial alterations in the early maturation of FMRPdeficient neural stem cells in fragile X syndrome and in the fmr1-KO mice.fmr1 gene ͉ fragile X mental retardation protein ͉ neurogenesis ͉ oscillations F ragile X syndrome is a common form of inherited mental retardation with an incidence of one in every 4,000 males (1). Many patients exhibit attention deficits, hyperactivity, autistic-like behavior, unusual responses to sensory stimuli, and epileptic seizures (for a review, see ref.2). The syndrome is caused by the absence or dysfunction of the fragile X mental retardation protein (FMRP), most often due to a mutation in the FMR1 gene leading to transcriptional silencing of the gene (2). FMRP is an RNA-binding protein that associates with polyribosomes and acts as a translational repressor of specific mRNAs at synaptic sites, and in that way it can regulate synapse growth and function (3-8). FMRP is highly expressed in the human central nervous system (9, 10). The absence of FMRP results in abnormalities of dendritic spines in fragile X patients (11)(12)(13)(14). The phenotype of the fmr1-knockout (KO) mice exhibits similarities with human fragile X syndrome (15,16). Abnormalities in synaptogenesis, synaptic structures and functions have been observed in the KO mice in vivo (17-21). One particularly interesting finding has been the augmentation of metabotropic glutamate receptor (mGluR)-dependent long-term depression in the fmr1-KO mice (22).Neural stem cells (NSCs) are multipotent, self-renewing cells that can be propagated in culture. Human NSCs provide a source of cells for in vitro studies attempting to elucidate neural mechanisms in the pathogenesis of human neurological disorders (23,24). In the present study, we exploited mouse and human NSCs to study the pathogenesis of fragile X syndrome and the cellular mechanisms leading to cognitive impairment and epilepsy. ...

Objective To assess the risk factors and outcome of pregnancy outside marriage in the 1990s, in conditions of a high percentage of extramarital pregnancies and high standard maternity care, used by the entire pregnant population. Design Hospital-based cohort study.Setting A university-teaching hospital in Finland.Population The 25,373 singleton pregnancies of known marital and cohabiting status.Methods Odds ratios (ORs) with 95% confidence intervals were calculated to estimate the effect of extramarital childbearing on pregnancy outcome. Multiple logistic regression analyses were conducted to control for confounding maternal risk factors. Main outcome measures Small-for-gestational age (SGA) infants, preterm birth (less than 37 completed weeks), low birthweight (LBW; under 2500 g). ResultsOf the study population, 67.5% were married and 32.5% were unmarried; 24.2% of all mothers were cohabiting. Unmarried status was strongly associated with social disadvantage and particular risk factors, specifically unemployment, smoking and previous pregnancy terminations, which in turn had an impact on obstetric outcome. There were significantly more SGA infants among unmarried mothers (P < 0.001), with an absolute difference of 45%; more preterm deliveries (P ¼ 0.001), with an absolute difference of 17.5%; and more LBW infants (P < 0.001), with an absolute difference of 26%. The differences in adverse pregnancy outcomes between study groups (i) all unmarried women, (ii) cohabiting women and (iii) single women, remained significant after multivariate analysis at adjusted ORs of 1.11, 1.11 and 1.07 for SGA, 1.17, 1.15 and 1.21 for LBW and 1.15, 1.15 and 1.29 for the preterm births, respectively. Conclusion Even in the 1990s when cohabitation was already common, pregnancy outside marriage was associated with an overall 20% increase of adverse outcomes, and free maternity care did not overcome the difference.

The objective of this study is to determine the risk of adverse pregnancy outcomes resulting from a true umbilical knot. We analyzed 288 singleton pregnancies with a true umbilical knot among the women who gave birth at Kuopio University Hospital from January 1990 to December 1999. Logistic regression analysis was used to compare pregnancy outcomes of the affected cases with those of the general obstetric population (n = 23,027). The incidence of true knot was 1.25% and it was associated with advanced maternal age, multiparity, previous miscarriages, obesity, prolonged gravidity, male fetus, long cord, and maternal anemia. The women having a fetus with a cord knot underwent cesarean delivery less frequently than unaffected controls. Fetal death and low Apgar score at 1 min occurred significantly more frequently in the study group than in the general obstetric population, the adjusted odds ratios being 3.93 (95% CI, 1.41-11.0) and 1.73 (95% CI, 1.10-2.72), respectively. Otherwise, the pregnancy outcome measures were comparable in the two groups. Fetuses with true umbilical knots are at a four-fold increased risk of stillbirth, but little can be done to prevent fetal deaths during pregnancy. Surviving fetuses with true knots are likely to suffer temporary distress during delivery, but affected newborns recover soon after birth. Thus, monitored vaginal delivery appears to be a safe option for fetuses with true knots.

II.

Background: Macrosomic fetuses represent a continuing challenge in obstetrics. Objectives: We studied maternal risk factors of fetal macrosomia and maternal and infant outcome in such cases. Methods: A retrospective cohort study was carried out with a total of 26,961 singleton pregnancies between 1989 and 2001. Records of 886 mothers who gave birth to live born infants weighing ≧4,500 g were compared to those of 26,075 mothers with normal weight (<4,500 g) infants. Multiple regression analysis was used to identify independent reproductive risk factors. Perinatal complications were also assessed. Results: The incidence of fetal macrosomia was 3.4%. Diabetes, previous macrosomic birth, postdatism (>42 weeks of gestation), obesity (BMI > 25 before pregnancy), male infant, gestational diabetes mellitus, and non-smoking were independent risk factors of fetal macrosomia, with adjusted risks of 4.6, 3.1, 3.1, 2.0, 1.9, 1.6, 1.4, respectively. In the macrosomic group, birth and maternal traumas occurred significantly more often than in the control group. However, records of subsequent pregnancies (n = 250) after the study period showed that a previous uncomplicated birth appeared to decrease complication risks. Conclusions: Most cases of fetal macrosomia occur in low-risk pregnancies and evaluation of maternal risks cannot accurately predict which women will eventually give birth to an overweight newborn. After an uncomplicated birth of a macrosomic infant, vaginal delivery may be a safe option for the infant and mother.