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The purpose of this prospective longitudinal study was to evaluate the growth of the fetal cerebellar volume by means of 3-D ultrasound to evaluate whether there is a difference between the volumes of the left and right cerebellar hemispheres, and to evaluate the intra- and interobserver reliability of two different techniques of volume measurement. Three-dimensional ultrasound examinations were performed every two to three weeks on 27 fetuses between 20 and 40 weeks' gestation. Measurements of the total cerebellar volume and of the left and right cerebellar hemispheres were done using the multiplanar technique. Multilevel analysis was used to determine the growth of cerebellar volume based on individual developmental trajectories and compare the volume of the right and left hemispheres of the cerebellum. The intra- and interobserver reliability was calculated for the multiplanar and VOCAL techniques in a subgroup of 10 fetuses. A nonlinear growth curve of cerebellar volume in normal pregnancy was generated. The cerebellar growth per two-week decreased from a gain of 51% of the first measurement at 20 weeks to a gain of 16% of the first measurement at 38 weeks. The left cerebellar hemisphere was significantly larger (12.3%, p < 0.01) than the right. The intraclass correlation coefficient for the measurements by the two techniques was 0.99. Intraobserver reliability: the intraclass correlation coefficient for the measurements using the multiplanar technique was 0.96 and 0.97 and for VOCAL it was 0.98 and 0.97 for the two observers, respectively. Interobserver reliability: the intraclass correlation coefficient for the measurements using the multiplanar technique was 0.97 and for VOCAL 0.98. Longitudinal growth curves based on individual developmental trajectories were generated for the cerebellar volume. The left fetal cerebellar hemisphere was found to be significantly larger than the right. Both multiplanar and VOCAL techniques had a good intra- and interobserver reliability and yielded very similar results.

Teratological investigations have demonstrated that agents that are relatively harmless to the mother may have significant negative consequences to the fetus. Among these agents, prenatal alcohol, nicotine or cannabis exposure have been related to adverse offspring outcomes. Although there is a relatively extensive body of literature that has focused upon birth and behavioral outcomes in newborns and infants after prenatal exposure to maternal smoking, drinking and, to a lesser extent, cannabis use, information on neurobehavioral and cognitive teratogenic findings beyond these early ages is still quite limited. Furthermore, most studies have focused on prenatal exposure to heavy levels of smoking, drinking or cannabis use. Few recent studies have paid attention to low or moderate levels of exposure to these substances. This review endeavors to provide an overview of such studies, and includes animal findings and potential mechanisms that may explain the mostly subtle effects found on neurobehavioral and cognitive outcomes. It is concluded that prenatal exposure to either maternal smoking, alcohol or cannabis use is related to some common neurobehavioral and cognitive outcomes, including symptoms of ADHD (inattention, impulsivity), increased externalizing behavior, decreased general cognitive functioning, and deficits in learning and memory tasks.

A direct link between antenatal maternal mood and fetal behaviour, as observed by ultrasound from 27 to 28 weeks of gestation onwards, is well established. Moreover, 14 independent prospective studies have shown a link between antenatal maternal anxiety/stress and cognitive, behavioural, and emotional problems in the child. This link generally persisted after controlling for post-natal maternal mood and other relevant confounders in the pre- and post-natal periods. Although some inconsistencies remain, the results in general support a fetal programming hypothesis. Several gestational ages have been reported to be vulnerable to the long-term effects of antenatal anxiety/stress and different mechanisms are likely to operate at different stages. Possible underlying mechanisms are just starting to be explored. Cortisol appears to cross the placenta and thus may affect the fetus and disturb ongoing developmental processes. The development of the HPA-axis, limbic system, and the prefrontal cortex are likely to be affected by antenatal maternal stress and anxiety. The magnitude of the long-term effects of antenatal maternal anxiety/stress on the child is substantial. Programs to reduce maternal stress in pregnancy are therefore warranted.

Objective: To compare salivary cortisol levels and maternal anxiety (general and pregnancy-specific) in the early and late second trimester of pregnancy between women who developed preeclampsia (PE) and women who remained normotensive., Design: Nested case-referent study. In a prospectively studied cohort of 250 pregnant women, nine women developed PE in late pregnancy. These nine patients were matched and compared with nine controls. Diurnal cortisol levels were obtained by collecting saliva samples at 17-18 and 27-28 weeks gestation. Salivary cortisol levels were determined by radioimmunoassay. Maternal anxiety was determined by Spielberger's State-Trait Anxiety Inventory (STAI) and a pregnancy-specific stress questionnaire., Results: For both patients and controls, a similar pattern of salivary cortisol excretion was observed. Salivary cortisol levels and anxiety scores (general and pregnancy-specific) did not differ significantly between patients and controls., Conclusions: Our findings do not lend support to a role for maternal anxiety or second trimester increases in circulating stress hormones in the pathogenesis of PE.

Pregnancies in women with type-1 diabetes are associated with an increased risk of developmental disorders. Despite extensive research, the toxicological mechanisms and pathogenesis of these disorders are far from explained. The whole rat embryo culture system was used to study the pathogenesis of malformations induced by culture in sera from diabetic women. In undiluted control sera, rat embryos with 4-8 initial somites developed well. During 26 hr of culture, on average 13 somites were formed per embryo, corresponding to the normal in vivo development. Only 3 out of 59 embryos had a significantly lower morphological score than did controls after culture. In the diabetic group no increased incidence of malformations was found, and development tended to be better than in control sera. Embryos cultured in sera derived from conventionally treated patients had a higher morphological score after culture than did embryos cultured in sera derived from women treated with an insulin pump. The sera of diabetic patients contained on average a fivefold higher insulin concentration than did control sera. However, addition of 300 mU/litre insulin to sera that contained on average 30 mU/litre did not improve the development of cultured embryos. The absence of malformations after culture in sera of diabetic women may relate to the fact that their blood glucose control was on average reasonably good.