Successful detection of the fetal electrocardiogram waveform changes during various states of singletons.

Accurate assessment of fetal well-being is one of the most important tasks for obstetricians. It is still difficult to measure fetal electrocardiogram (ECG) during fetal movements. Recently, a new method, blind source separation with reference signals, was proposed for stable measurements. This method distinguishes weak signals from noisy mixed signals with little information about the sources. The aim of this study is to estimate the ability of this method for fetal ECG monitoring and to establish standard fetal ECG electrocardiogram values of normal singletons including during fetal movement. The subjects enrolled were 167 pregnant women with normal single pregnancy from 18- to 41-week gestation, who regularly visited Tohoku University Hospital, and 12 pregnant women with fetal abnormality. Fetal signals were successfully separated in 163 of 179 subjects at 91.1% success rate regardless of fetal movements. Time intervals of ECG (P, PR and QRS intervals and QTc) were measured. The standard curves of each interval through the gestational period were obtained. The data in active phase were compared to that in rest phase and the data obtained from normal and abnormal fetuses were investigated. PR intervals in the rest phase were prolonged compared to those in the active phase. Fetal ECG showed anomalous values such as PR interval or QTc prolongation in the abnormal fetuses. The fetal ECG was measured by the new method with or without fetal movements, and the standard fetal ECG values have been established. This study provides a foundation for further detailed clinical studies.

Aberrant expression of hypoxia-inducible factor 1α in the fetal heart is associated with maternal undernutrition.

Maternal undernutrition during pregnancy is a risk factor that impairs fetal growth and causes cardiovascular diseases. However, the underlying mechanism is still unknown. In this study, we evaluated the effect of maternal undernutrition on the expression levels of transcription factors in the fetal heart. Female mice were given low protein or regular food from 2 weeks before mating and during their pregnancy. The fetal hearts were collected on day 17.5 of gestation, about 1-2 days before birth. Maternal undernutrition resulted in a significant increase in the relative heart weight (heart weight/body weight) in female fetuses, but not in male fetuses. Microarray analysis revealed that expression levels of mRNAs for 133 transcription factors were changed in the fetal heart under maternal undernutrition. Among them, we focused on hypoxia-inducible factor 1 alpha (HIF1α) that is involved in the pathogenesis of cardiovascular diseases on adulthood. Quantitative real-time PCR analysis showed that the expression level of HIF1α mRNA was increased about 1.3-fold in male fetal heart under maternal undernutrition, but remained unchanged in female heart. Moreover, maternal undernutrition increased the mRNA level of prolyl hydroxylase 1 (PHD1), which contributes to degradation of HIF1α, in male heart but not in female heart. Immunohistochemical analysis showed the accumulation of HIF1α protein in the fetal heart of both sexes under maternal undernutrition, without the induction of HIF1α mRNA expression in female heart. These results suggest that maternal undernutrition may induce HIF1α expression in the fetal heart through the distinct mechanisms depending on the sex.

Maternal undernutrition with vaginal inflammation impairs the neonatal oligodendrogenesis in mice.

Maternal undernutrition and infection during pregnancy may impair development of oligodendrocytes, thereby increasing risks of neuropsychiatric disorders of their children. We analyzed the effects of those risk factors on oligodendrogenesis in fetal and neonatal brains. Female mice were given low-protein or regular food for 2 weeks before their pregnancy. On the 14th day of pregnancy, they received a transvaginal injection of lipopolysaccharide to induce inflammation or control solution, consisting of four groups, depending on nutritional conditions with or without vaginal inflammation. We collected fetal brains on embryonic day (E) 17 for evaluating oligodendrocyte precursor cells (OPCs) and neonatal brains on postnatal day (P) 7 for evaluating mature oligodendrocytes. OPCs and mature oligodendrocytes were identified as positive immunostaining for oligodendrocyte-lineage transcription factor 2 and myelin basic protein, respectively. There was no difference in the number of OPCs in E17 brains among the four groups, suggesting that nutritional restriction with or without inflammation exerts no noticeable influence on the differentiation of OPCs. However, the number of mature oligodendrocytes was decreased in P7 brains obtained from nutrient-restricted mice with inflammation, suggesting that their combination impairs oligodendrogenesis in the neonatal brain. We also analyzed reactive astrocytes that express both glial fibrillary acidic protein and nestin for evaluating brain inflammation. The population of reactive astrocytes was increased in P7 brains derived from mice with LPS injection, irrespective of nutritional restriction, indicating that maternal vaginal inflammation induces neonatal brain inflammation. The maternal management of both nutrition and infection is crucial to prevent neuropsychiatric disorders of the children.