The effects of maternal exercise on fetal oxygenation and feto-placental growth

Sustained bouts of maternal exercise during pregnancy cause an acute reduction in oxygen and nutrient delivery to the placental site. The decreased flow also initiates a slight fall in intervillous and fetal pO2 which initiates a fetal sympathetic response. This, coupled with hemoconcentration and improved placental perfusion balance, maintains fetal tissue perfusion and oxygen uptake. Exercise training during pregnancy (regular bouts of sustained exercise) increases resting maternal (and perhaps fetal) plasma volume, intervillous space blood volume, cardiac output and placental function. These changes buffer the acute reductions in oxygen and nutrient delivery during exercise and probably increase 24 h nutrient delivery to the placental site. Thus, the effect of any given exercise regimen on fetal growth and size at birth is dependent on the type, frequency, intensity and duration of the exercise as well as the time point in the pregnancy when the exercise is performed. Maternal carbohydrate intake is yet another modifying factor. Beginning a moderate exercise regimen increases both anatomic markers of placental function and size at birth while maintaining a rigorous exercise regimen throughout pregnancy selectively reduces growth of the fetal fat organ and size at birth. Likewise, decreasing exercise performance in late-pregnancy increases size at birth while increasing exercise performance decreases it. Finally, the infants born of exercising women who eat carbohydrates which elevate 24 h blood glucose levels are large at birth irrespective of exercise performance.     

Metabolism of pregnenolone sulfate in feto-placental unit

In order to study the metabolic fate of circulating pregnenolone sulfate (P5S) during pregnancy, 30 mg of newly synthesized tetra (2,2,4,6)-deuterated P5S was administered to the maternal vein 60 minutes prior to cesarean section at term. All pregnant women were volunteers and had been informed of nature of this study. The placenta, maternal urine and blood samples from maternal vein (MV), umbilical cord (U) were collected and deuterated metabolites were analysed by gas chromatography mass spectrometry with a multiple ion detector. Total amounts of metabolites were measured and the ratio of deuterated steroid to the total amounts were calculated (d%). d% of P5S, 16 alpha OH-P5S, 17 alpha OH-P5S, 20 alpha-dihydro-P5S (20P5S), 20P5 and progesterone (P4) in MV were 84.5, 51.6, 95.5, 85.1, 71.2 and 10.9%, respectively. In the placental tissue, 20P5, 20P4 and P4 were also found and d% of these steroids were calculated as 16.1, 3.2 and 3.1%. Only P4 was found with d% of 11.2% in U. In the urine collected for 2 hours after deuterated P5S administration, P5S (40.6%), 20P5S (56.6%) and pregnanediol (34.8%) were identified. Deuterated C19, C18 steroids were not detected in any of the samples studied. When 30 mg of non labeled P5S was also administered to MV at term, the levels of P5S, 20P5S, P4 and 20P4 in MV rose, but the levels of DHA-S were not changed. These results indicate that the circulating P5S in MV can be a precursor of 20P5S, 17P5S, 16P5S, 20P4 and P4, but can not be the precursor of C19, C18 steroid.     

Adrenomedullin concentrations in early 2nd-trimester amniotic fluid: relation to preterm delivery and fetal growth at birth

OBJECTIVE: The purpose of this study was to evaluate whether adrenomedullin concentrations in the early 2nd-trimester amniotic fluid predict preterm delivery or fetal growth at birth. METHODS: The adrenomedullin concentrations in early 2nd-trimester amniotic fluid were measured in 70 pregnancies with term delivery and in 3 pregnancies with preterm delivery. Total and free adrenomedullin concentrations were measured from early 2nd-trimester amniotic fluid samples using an immunoradiometric assay. RESULTS: The amniotic fluid total adrenomedullin concentrations in women with preterm delivery were significantly higher (129.7 +/- 19.6 fmol/ml) than those in women with term delivery (92.5 +/- 28.2 fmol/ml; p < 0.05). There were no significant differences for amniotic fluid free adrenomedullin concentrations and free/total adrenomedullin ratios between the two groups. Total or free adrenomedullin concentrations in the early 2nd-trimester amniotic fluid showed an inverse correlation both with birth weight (r = 0.27, p < 0.05, and r = 0.21, p < 0.05) and height (r = 0.30, p < 0.05, and r = 0.28, p < 0.05). There were no correlations between placental weight and total or free adrenomedullin concentrations in the early 2nd-trimester amniotic fluid. CONCLUSIONS: These results suggest that adrenomedullin concentrations in the early 2nd-trimester amniotic fluid might be related to further in utero fetal growth and that high levels of adrenomedullin in the early 2nd-trimester amniotic fluid may be involved in the occurrence of preterm delivery.     

Clinical significance of the feto-placental unit during pregnancy and parturition

Theoretical basis of measurement of estriol during pregnancy. It was clarified that the feto (adrenal and liver)-placental unit plays an important role in the biosynthesis of estriol during pregnancy. The theoretical basis of the usefulness of estriol estimation in maternal urine as the indicator of fetal viability is therefore established, and a simplified estriol assay (LAIR-3 minutes method) was developed. As to the steroid values in the amniotic fluid during pregnancy, high level of progesterone (P4) in the first trimester and prominent rises of DHA-S and estriol values near term were shown. Furthermore, transference of amniotic DHA-S to the mother through the amniotic membrane was demonstrated by the in vivo study using deuterium labeled DHA-S given in the amniotic fluid. In vivo study using deuterated pregnenolone sulfate (P5-S) given in the maternal circulation demonstrated that maternal P5-S was partially used as the precursor of placental P4. Therefore, it is suggested that the precursor of placental P4 is mainly derived from the feto-placental side rather than the maternal one. Changes of steroidal environment near term. Steroid hormone assay by gas chromatography mass-spectrometry using deuterium labeled compound as internal standard was developed, and (fetal adrenal) steroid values in maternal blood were measured. DHA-S, 16 alpha-OH- DHA-S and estriol values increase in the prepain and labor period and P4 and 20 alpha-OH-P4 values decrease during labor. In vivo study using deuterium labeled DHA-S given to the fetal side in the perinatal period demonstrated that DHA-S originated from fetal adrenal transferred to the mother through placenta without being subjected to the aromatisation. The elevation of uterine sensitivity to oxytocin in the perinatal period is closely related to both the increases of DHA-S and estriol levels, and the decrease of P4 values in the maternal blood. As to the hormonal factors of hypothalamo-posterior pituitary system, the levels of estrogen stimulated neurophysin (ESN) and oxytocin in the maternal blood elevated parallel with the increase of estrogen level in the prepain period. The administration of DHA-S (100mg, twice a week) in the perinatal period accelerate the maturation of uterine cervix with concomitant augmentation of DHA-S concentration and increased proline hydroxylase activity in the cervical tissue.(ABSTRACT TRUNCATED AT 400 WORDS)     

Color-Doppler for predicting vascular resistance to feto-placental blood flow and fetal well-being

Aloka Color-Doppler, model SSD-860, was used to observe the blood velocity waveforms in the umbilical artery and in the fetal descending thoracic aorta in 139 normal pregnant women from 16th to 40th week and 30 patients suffering from pregnancy induced hypertension (PIH syndrome). The ratio of systolic to diastolic peak flow (A/B) reflected the fetoplacental vascular resistance and peripheral resistance. The results demonstrated that the placental resistance in PIH syndrome and IUGR were much higher than that in normal pregnancy. The placental resistance decreased when patients condition improved after treatment and vice versa. This suggests that fetal blood velocity waveforms (FVW) is of great value in the intensive monitoring of IUGR fetuses. The blood velocity FVW was also of great value in evaluating the curative effects on PIH patients.     

Serum leptin concentrations during pregnancy and their relationship to fetal growth

Objective: To test the hypothesis that maternal and cord serum leptin concentrations correlate with birth weight of infants.Methods: Pregnant women (n = 135) of low socioeconomic status who delivered full-term infants were selected from more than 1500 women who participated in a study to identify factors related to fetal growth restriction (FGR). They were divided into two groups based on their infants being classified as having FGR (n = 66) or not (n = 69), and each group was divided further into three subgroups based on prepregnancy body mass index (BMI): less than 19.8, 19.8–28.9, and 29 or more. Sample estimations indicated that 20 subjects per subgroup would be adequate to detect 50% difference in leptin concentrations.Results: Mean maternal serum leptin concentrations adjusted for BMI were highest at approximately 22–27 weeks' gestation (29.8 ng/mL) and declined thereafter until term (25.2 ng/mL). Leptin concentration and prepregnancy BMI correlated significantly. We found neither significant difference in leptin concentrations between the subjects with and without FGR infants nor significant correlation between maternal leptin concentrations and birth weight of infants. Mean cord serum leptin concentration (10.8 ng/mL) was lower than maternal concentrations and correlated significantly with birth weight (r = .61, P < .001).Conclusion: Our findings suggest that maternal leptin concentration during pregnancy is not an accurate indicator of fetal growth. Cord serum leptin concentrations were lower than maternal serum concentrations and correlated significantly with birth weight.     

Intact feto-placental growth in microRNA-210 deficient mice

MicroRNA-210 (miR-210) has been implicated in homeostatic adaptation during hypoxia. We hypothesized that miR-210 deficiency impacts feto-placental growth. As expected, mir-210 knockout (ko) mice exhibited markedly reduced placental miR-210 expression, compared to wild-type (wt) mice. Mating of mir-210 heterozygotes resulted in near Mendelian progeny distribution, with insignificant differences between wt and ko animals with regard to embryo or placental weight and gross morphology. Intriguingly, exposure of mice to non-severe hypoxia (O₂ = 12%) between E11.5-E17.5 reduced placental miR-210 expression, with slight expression changes of some miR-210 target mRNAs. Thus, miR-210 is likely dispensable for feto-placental growth in normoxia or non-severe hypoxia.     

A prospective study of pregravid oral contraceptive use in relation to fetal growth

OBJECTIVE: Because oral contraceptives are so widely used, any health consequences may have substantial public health implications. Whether pregravid oral contraceptives could affect subsequent pregnancies has not been adequately studied. The study objectives were to examine whether pregravid oral contraceptive use affects fetal growth and pregnancy hormone levels. DESIGN: A prospective study of pregnant women followed through pregnancy. SETTING: A major teaching hospital in Boston, USA. POPULATION: Two hundred and sixty Caucasian pregnant women, with a mean age of 31, and a parity of no more than two. Seventy-nine percent of the women were pregravid oral contraceptive users. METHODS: Exposure and covariate data were collected through structured questionnaires. Blood was drawn for hormonal analysis during the 16th and 27th gestational week. Information on pregravid oral contraceptive use included duration and recency of use, and oral contraceptive formulation. Multivariate regression models were used to examine the effect of pregravid oral contraceptive use on birth outcomes and the studied pregnancy hormones. MAIN OUTCOME MEASURES: Birthweight, placental weight, gestational age, pregnancy hormone levels of oestriol and progesterone at 16th and 27th gestational week. RESULTS: Adjusting for confounders, pregravid oral contraceptive use increased birthweight (mean difference =+207.3 g, 95% CI =+77.6 to +337.1) and placental weight (mean difference =+64.9 g, 95% CI =+13.0 to +116.9) compared with never use. Women with prior oral contraceptive use had higher levels of serum progesterone (P= 0.002) and oestriol (P= 0.12) at the 27th gestational week measurement. The effect on birthweight, placental weight and hormones was stronger among those using oral contraceptives in the previous year and those using a high progestin/high oestrogen potency preparation. CONCLUSIONS: Pregravid oral contraceptive use is positively associated with fetal growth, and this effect may be mediated through oestriol and progesterone.     

Comparison of trace element concentrations in cancerous and noncancerous human endometrial and ovary tissues

Question of whether trace metal concentrations in tissues are increased or decreased in cancerous patients in comparison with noncancerous patients has not been answered yet, due to the fact that the data known in this field are rare and have contradictory results. Although Zn and Cu concentrations in serum and tissues of cancerous patients have extensively been studied, the precise role of these metals in carcinogenesis is not clearly understood. There are few studies on the concentrations of essential and toxic trace/minor metals in human tissue samples in comparison with serum and plasma samples. Trace metal concentrations including Cd, Cu, Zn, Fe, Mg, Ca, and Ni in both cancerous and noncancerous endometrial, ovary, and cervix uteri tissues were determined by atomic absorption spectrometry. The tissue samples were digested by using microwave energy. Slotted tube atom trap was used to improve the sensitivity of copper and cadmium in flame atomic absorption spectrometry determination. The concentrations of iron in cancerous endometrial tissues were found to be significantly higher than those in noncancerous samples (P < 0.01). On the contrary Fe, Zn concentration in cancerous endometrial tissue was found to be lower significantly than those in noncancerous samples (P= 0.005), whereas the other studied metals were not observed different. Furthermore, Cu and Ca concentrations in cancerous ovary samples were observed to be higher than those in noncancerous ovary tissues (P < 0.01 for Cu and P= 0.1 for Ca), whereas Mg, Fe, and Zn levels in cancerous ovary samples were not found to be different than those in noncancerous tissues.     

Severe pre-eclampsia is associated with abnormal trace elements concentrations in maternal and fetal blood

Objective: The study was aimed to compare trace elements concentrations in women with and without severe pre-eclampsia (PE). Methods: A prospective case-control study was conducted comparing 43 parturients with severe PE (who received magnesium sulfate [MgSO4]) and 80 healthy parturients and their newborns, matched for gestational age and mode of delivery. Inductively coupled plasma mass spectrometry (ICPMS) was used for the determination of zinc (Zn), copper (Cu), selenium (Se) and magnesium (Mg) levels in maternal as well as arterial and venous umbilical cord serum. Results: Zn levels (µg/L) were significantly higher in fetal arterial and venous blood of the PE group (947.3?±?42.5 vs. 543.1?±?226, 911.1?±?220.2 vs. 422.4?±?145, p?<?0.001; respectively). Se levels (µg/L) were significantly lower in maternal and fetal arterial and venous cord blood of the PE group (98.6?±?24.2, 110.7?±?19.4, 82?±?17.8 vs. 111.6?±?17.6, 82.1?±?17.4 vs. 107.1?±?25.7, p?<?0.001; respectively). Cu levels (µg/L) were significantly lower in fetal arterial and venous cord blood (581.6?±?367.4 vs. 949?±?788.8, p?=?0.022, 608.3?±?418.1 vs. 866.9?±?812.6, p?=?0.001 respectively) but higher in maternal blood (2264.6?±?751.7 vs. 1048?±?851.1, p?<?0.001). These differences remained significant while controlling for the mode of delivery. Mg levels were significantly higher in the PE group as compared with the control group. Conclusions: Severe PE is associated with abnormal concentrations of Zn, Cu and Se. Therefore, trace elements may have a crucial role in the pathogenesis of severe PE.     

Perinatal sclerostin concentrations in abnormal fetal growth: the impact of gestational diabetes

Objective: To prospectively evaluate maternal and cord blood concentrations of sclerostin – an osteocyte-secreted factor, inhibiting osteoblast differentiation and bone formation and associated with adverse metabolism – in pregnancies with normal and abnormal fetal growth.

Methods: Plasma sclerostin concentrations were determined by ELISA in 80 maternal and 80?cord blood samples from asymmetric intrauterine-growth-restricted (IUGR, n?=?30), large-for-gestational-age (LGA, n?=?30), and appropriate-for-gestational-age (AGA, n?=?20) singleton full-term pregnancies. Fourteen out of 30 mothers with LGA offspring presented with gestational diabetes mellitus (GDM).

Results: Maternal and fetal sclerostin concentrations did not differ among LGA, IUGR, and AGA groups. Fetal concentrations were higher than maternal. In LGA group, maternal concentrations were elevated in cases of GDM (b?=?13.009, 95%CI 1.425–24.593, p?=?.029). In a combined group and the IUGR group, maternal concentrations were elevated in older mothers (b?=?0.788, 95%CI 0.190–1.385, p?=?.010, and b?=?0.740, 95%CI 0.042–1.438, p?=?.039, respectively).

Conclusions: Maternal and fetal sclerostin concentrations may not be differentially regulated in pregnancies complicated by abnormal fetal growth. Circulating maternal levels are higher in cases of GDM, probably implying reduced bone formation. Sclerostin up-regulation with aging may be one of the molecular pathways responsible for the observed age-related decline in bone synthesis, leading to accelerated bone loss in humans.     

胰岛素样生长因子—I与胎儿出生体重的关系

目的 了解胰岛素生长因子－Ｉ（ＩＧＦ－Ｉ）在胎儿生长发育中所起的作用,方法 选择１７１例产妇及其所分娩的新生儿１６４例,根据出生体重将新生儿分为大于胎龄儿（ＬＧＡ）组,产妇７７例,新生儿６４例,适于胎龄儿（ＡＧＡ）组：产妇５９例,新生儿５９例;小儿胎龄儿（ＳＧＡ）组：产妇３５例,新生儿４３例,用放射免疫法测定血清中ＩＧＦ－Ｉ的浓度。结果 母血中ＩＧＦ－Ｉ浓度均高于脐血,两者间存在浓度梯度（Ｐ〈０．     

Maternal-fetal disparity at multiple minor histocompatibility loci affects the weight of the feto-placental unit in mice

Inbred mice from selected unrelated and congenic strains were mated to determine the relative effects of maternal-fetal disparity at major histocompatibility complex (H-2) and non-H-2 minor histocompatibility antigens on the feto-placental unit at 14 days of gestation. A significant increase in weight of the feto-placental unit was observed only when mother and fetus differed at multiple minor histocompatibility loci. No increase in the weight of the feto-placental unit was observed when mother and fetus differed only at H-2. These results suggest that immunostimulation of the fetus results from a maternal response to minor histocompatibility antigens and not to H-2 antigens.