Diurnal rhythms of fetal and maternal heart rate in the baboon.

To investigate the organization of diurnal rhythmicity during gestation, the relationship between daily cycles of maternal and fetal heart rate were measured in long-term studies of healthy chronically instrumented pregnant baboons. In each of six pregnancies, hourly mean values over a 168 h time series were obtained during a 7 to 10 day interval between 135 and 160 days of gestation. Data were modeled by a least squares fit to a cosine function with a period of 24 h. Hourly mean heart rate in the fetus ranged from 161 to 172 bpm (167.9+/-0.6 bpm), and the mother from 105 to 125 bpm (107.9+/-1.4 bpm). The amplitude of the daily fluctuations were 15 to 25 bpm for the fetuses and 25 to 60 bpm for the mothers. The relation between time series data and model estimates were significant (P < 0.001) in all cases with aggregate r2 = 0.747 for fetuses and 0.737 for the mothers. On average the time of day of the peak in fetal heart rate (15:05+/-0.3 h) was about 45 min after the maternal peak (14:21+/-0.4 h). This phase delay was significant (t = 2.63, P < 0.05). There was significant (P < 0.01) diurnal periodicity for each of six parameters used to assess different aspects of fetal heart rate variability with peak variability at night (23:00 to 2:00). Thus, during the latter third of pregnancy in both the maternal and fetal baboon 24 h periodicities of heart rate are present with peak rates in the midafternoon. The daily rhythms in fetal heart rate are linked with periodicities in maternal heart rate with a phase delay in the majority of cases. The synchrony of 24 h fluctuations in rate with parameters of rate variability is consistent with diurnal input into the fetal autonomic nervous system.     

Altered placental and fetal expression of IGFs and IGF-binding proteins associated with intrauterine growth restriction in fetal sheep during early and mid-pregnancy

The insulin-like growth factors (IGFs) are postulated to be altered in association with the development of intrauterine growth restriction (IUGR). The present studies examined placental and fetal hepatic mRNA concentration of components of the IGF system at two time points (55 and 90 d gestational age, dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90 dGA and were unaffected by treatment. Umbilical vein insulin concentrations tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was increased at 90 dGA in HT placentae (p < 0.05), while cotyledon concentrations were constant over gestation and unaltered by treatment. In control cotyledons, IGF-II mRNA concentration increased (p < 0.01) and IGFBP-3 decreased between 55 and 90 dGA (p < 0.01). Cotyledon IGF-II and caruncle IGFBP-4 mRNA were elevated at 55 dGA in HT placentae compared with control (p < 0.01 and p < 0.05 respectively). Fetal hepatic IGF-I, IGFBP-2, -3 and -4 concentrations rose over gestation (p < 0.05), but there were no treatment effects. These data suggest that changes in placental IGF expression in early and mid gestation may predispose the pregnancy to placental insufficiency, resulting in inadequate substrate supply to the developing fetus later in gestation.     

Bidirectional placental transfer of glucose and its turnover in fetal and maternal sheep.

Glucose biokinetics were assessed simultaneously in the pregnant ewe and its fetus by a primed constant infusion of 2-3H glucose and U-14C glucose. Late in gestation fetal glucose turnover was 27.3 +/- 3.7 mg/min; expressed in terms of fetal weight this is 6 to 10 mg/kg/min. In the fed state the results indicated that all of the fetal glucose turnover was derived from the mother via placental transfer and there was no evidence that the fetus was capable of glucose production. Maternal glucose turnover was 145.6 +/- 9.3 mg/min (2.8 mg/kg/min). There was a significant amount of glucose (16.3 +/- 2.3 mg/min) transferred from the fetus to the mother. This feto-maternal transfer of glucose accounted for 11% of the maternal glucose turnover and approximately 50% of the total glucose coming to the fetus from the mother. This study provides the first in vivo simultaneous quantification of the bidirectional glucose transfer across the placenta.     

Alterations in human fetal hematopoiesis are associated with maternal HIV infection.

In the majority of adult and pediatric patients with AIDS, hematologic abnormalities including leukopenia, anemia, and thrombocytopenia are commonly observed. In addition to these findings, changes in hematopoietic progenitor cells occur, including a reduction of multipotential-forming units, granulocyte-macrophages, macrophage as well as eosinophil colony-forming units, and bone marrow erythroid burst-forming units. This study examined alterations in human fetal liver hematopoiesis in 2nd trimester abortuses from human immunodeficiency virus (HIV)-seropositive women. The differentiation and growth potential of hematopoietic cells in vitro were monitored. Upon initial isolation, some populations of liver hematopoietic cells from abortuses of HIV-seropositive women were significantly decreased when compared to age-matched samples from fetuses of normal females including the percentage of early T cells [cluster of differentiation (CD)2], B cells (CD19), and early monocytes (CD14). A decrease in multipotent progenitors (CD34), myelomonocytes (CD33), and panleukocytes (CD45) was also observed. In contrast, after 21 d in culture, cells from HIV abortuses demonstrated an increase in the percentage of CD14 cells when stimulated with erythropoietin and granulocyte-monocyte colony-stimulating factor, as well as an increase in CD45 phenotype after exposure to granulocyte-monocyte colony-stimulating factor alone. These samples showed a persistence of erythropoietic elements (transferrin and CD36 phenotype) when compared to normal controls. No significant difference in the in vitro growth of hematopoietic progenitors (bone marrow erythroid burst-forming units, granulocyte-macrophage colony-forming units, and multipotential forming units) between these samples and normal controls was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

The duration of maternal cigarette smoking, fetal and placental disorders

Data from a large prospective study of pregnancy were used to determine whether the number of years a mother had smoked cigarettes influenced the development of common fetal and placental disorders. Three disorders increased in frequency when mothers had smoked for more than 6 yr: placenta previa +143%, abruptio placentae +72% and large placental infarcts +37% (all P less than 0.05). Mothers' current smoking habits had a smaller influence on the frequency of these disorders, and the effects of smoking were largely independent of maternal pregnancy weight gain. The placentas of smokers had microscopic evidences of underperfusion from the uterus. The placental abnormalities were influenced by both the number of years mothers had smoked and by their current smoking habits.     

Effects of fetal decapitation upon porcine placental metabolism. Evidence for a fetal influence in placental metabolism

This experiment was performed to determine if the fetus can influence its placental metabolism. Fetal pigs were decapitated at 45 days of gestation and their placentas compared at 110 days to within litter controls. No histological or histochemical differences were observed. Glycogen levels were elevated in the fetal placenta of decapitated pigs by 107%. Fatty acid synthesis was increased in the fetal placenta of decapitated animals (12.9 +/- 1.5 vs. 3.4 +/- 0.7 nmol acetate units/100 mg/2 h). Fetal decapitation increased fetal placental fatty acid esterification by 43% and oxidation by 125%. The altered lipid metabolism of the fetal placenta was reflected in enzymes associated with substrate utilization (pyruvate kinase and lactate dehydrogenase). Maternal placenta lipogenesis was also altered by fetal manipulation. Leucine conversion to its alpha ketoacid was increased in the fetal placenta of the decapitated pigs (14.8 +/- 1.7 vs. 8.6 +/- 1.4 nmol/100 mg/2 h) indicating amino acid metabolism was affected by this treatment. The ability of an altered fetal endocrinology and metabolism to affect the placental metabolism supports the concept of a fetal influence on placental metabolism.     

The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development

The human growth hormone (hGH)/human placental lactogen (hPL) gene family, which consists of two GH and three PL genes, is important in the regulation of maternal and fetal metabolism and the growth and development of the fetus. During pregnancy, pituitary GH (hGH-N) expression in the mother is suppressed; and hGH-V, a GH variant expressed by the placenta, becomes the predominant GH in the mother. hPL, which is the product of the hPL-A and hPL-B genes, is secreted into both the maternal and fetal circulations after the sixth week of pregnancy. hGH-V and hPL act in concert in the mother to stimulate insulin-like growth factor (IGF) production and modulate intermediary metabolism, resulting in an increase in the availability of glucose and amino acids to the fetus. In the fetus, hPL acts via lactogenic receptors and possibly a unique PL receptor to modulate embryonic development, regulate intermediary metabolism and stimulate the production of IGFs, insulin, adrenocortical hormones and pulmonary surfactant. hGH-N, which is expressed by the fetal pituitary, has little or no physiological actions in the fetus until late in pregnancy due to the lack of functional GH receptors on fetal tissues. hGH-V, which is also a potent somatogenic hormone, is not released into the fetus. Taken together, studies of the hGH/hPL gene family during pregnancy reveal a complex interaction of the hormones with one another and with other growth factors. Additional investigations are necessary to clarify the relative roles of the family members in the regulation of fetal growth and development and the factors that modulate the expression of the genes.     

Prolonged preterm rupture of fetal membranes, a consequence of an increased maternal anti-fetal T cell responsiveness

A fetus, although semi-allogeneic, is usually accepted by the maternal immune system. However, complications, including alloresponsive mechanisms, are thought to be potentially detrimental for a successful pregnancy. Therefore, we compared allogeneic T cell responses of nonpregnant women with the response of healthy pregnant women and pregnant women who have various gestation-associated diseases. Peripheral blood mononuclear cells (PBMCs) of all three groups were stimulated with PBMCs from unrelated volunteers. Pregnant women had significantly reduced stimulation indices (SIs) compared with nonpregnant women. Exposing PBMCs from pregnant women to PBMCs of their own fetus led to a further significant decrease of SIs. Among the two groups of pregnant individuals, SIs of women with prolonged preterm rupture of fetal membranes (PPROM) were significantly higher when the maternal PBMCs were stimulated with PBMCs of their own fetus. This phenomenon could not be observed after stimulation with PBMCs from unrelated volunteers. In addition, an increased humoral immune response was assessed for women with PPROM in comparison with women with uncontrollable preterm labor. Our results revealed a strongly reduced allogeneic T cell response of PBMCs from pregnant women that was further down-regulated when PBMCs from their own fetus were used as stimulators. By contrast, data from women with PPROM suggest an increased maternal T cell response specifically toward the fetal HLA antigens.     

Placental transfer and fetal urinary excretion of gentamicin during constant rate maternal infusion.

Placental transfer and fetal urinary excretion of gentamicin was studied in midtrimester goat and human previable fetuses during constant rate maternal infusion with the drug. Gentamicin was not detected in the serum of any of the goat fetuses, even when maternal serum concentrations ranged from 15.2 mug/ml to 20.9 mug/ml. However, gentamicin was present in the amniotic fluid of four animals. Gentamicin was also present in fetal urine collected from three animals. In contrast human fetal central venous serum concentrations of gentamicin were 21-37% of those in maternal serum after constant rate infusion of the mother. In addition, gentamicin was present in human fetal urine in concentrations 2-- 3 times those in fetal serum. The observed difference in fetal serum concentration of gentamicin between the two species represents a difference in placental permeability to gentamicin and/ or a difference in fetal renal clearance of the drug.     

Arterial and venous Doppler in the diagnosis and management of early onset fetal growth restriction

Key issues in the management of early onset fetal growth restriction (IUGR<34 weeks) are accurate diagnosis and assessment of fetal well-being to optimize timing of delivery by weighing fetal vs. neonatal risks. Cardiovascular, behavioral and fetal heart rate patterns in IUGR follow a predictable progression that corresponds with the severity of compromise. Umbilical artery (UA) Doppler primarily serves as a placental function test providing insufficient information to solely direct perinatal management. Venosus Doppler is an independent predictor of stillbirth and acidemia and needs to be examined when the UA index is elevated, especially if end-diastolic velocities are absent. Neonatal outcomes are primarily determined by gestational age and their antenatal prediction is too ineffective to guide management. Abnormal venous Doppler, biophysical profile score and mean minute variation of the fetal heart rate are strong predictors of fetal compromise therefore favoring delivery. Randomized trials indicate that delayed delivery has little effects on short-term outcome while producing a trend towards improved early childhood neurodevelopment. This stresses the need for excellent fetal surveillance techniques and their ongoing investigation through randomized management trials.     

Influence of maternal stress on fetal behavior and brain development

The very early establishment of certain sensory faculties turns the fetus into a being capable of perceiving multiple stimuli. This perceptive capability forms part of many interchanges between the mother and her developing child. These interchanges are doubtless not only biological and metabolic in nature, but also sensorial and sensitive. The importance of a good quality of psychoaffective communication between mother and child during pregnancy has been shown to be decisive for fetal growth and also for the perinatal period and further development of the child. Maternal psychological stress leads to adverse pregnancy outcome. Chronic anxiety causes an increased stillbirth rate, fetal growth retardation and altered placental morphology. Experimental studies have demonstrated a relationship between specific episodes of maternal psychological stress and exacerbation of fetal asphyxia in utero. It is concluded that all the psychoaffective interchanges between the mother and child are decisive for harmonious fetal growth and brain development.     

Diabetes in pregnancy: decreased placental blood flow and disturbed fetal development in the rat

Placental blood flow was measured with the aid of radioactive microspheres, in normal (N) and manifest diabetic (MD) rats, and related to fetal body growth and incidence of congenital malformations. The total blood flow in the placentae of the MD rats was decreased to about one-half of the normal flow on gestational days 20 and 22. The placentae of the MD offspring were enlarged, whereas the fetuses in this group were smaller than normal. Thus, the placental blood flow per placental weight was drastically decreased in the MD fetuses on both days 20 and 22. In contrast, the placental blood flow per fetal weight was not different in the N and MD groups on gestational day 20 whereas it was decreased in the MD offspring on gestational day 22. Placental blood flow in the malformed fetuses of the MD group did not differ significantly from that in the nonmalformed MD fetuses.     

胎儿生长受限对出生后体格、智力和行为发育的影响

随着医学技术的不断进步,胎儿生长受限(FGR)患儿的存活率不断提高,随之而来的是对这部分患儿长期体格和智能发育的不断关注.多数FGR患儿在生后会有一个明显的追赶生长过程,但仍有少部分会出现终生矮小,目前我国批准使用生长激素改善其终身高已经取得了良好效果.笔者发现这部分患儿在智能发育上也存在部分缺陷,到学龄期出现注意力集中困难、多动、冲动和学习障碍的比例也相当高.该文就此方面的研究现状作一介绍.