Fetal cells in maternal blood of pregnancies with severe fetal growth restriction

The aim of this study was to examine whether, in pregnancies with severe early onset fetal growth restriction, the number of fetal erythroblasts in maternal blood is increased. The percentage of fetal erythroblasts in maternal blood, enriched by triple density gradient centrifugation and anti-CD71 magnetic cell sorting, was determined in 10 singleton pregnancies with severe intrauterine growth restriction in which there was Doppler ultrasound evidence of impaired placental perfusion. The values were compared to those of 10 normal pregnancies at the same gestational range of 22-26 weeks. In the growth restricted pregnancies the median number of fetal erythroblasts per 100 nucleated cells in maternal blood enriched for fetal cells was significantly higher than the median value in the control pregnancies (8.5% compared with 1%; P < 0.001). These data suggest that impaired uteroplacental perfusion and severe fetal growth restriction may be associated with placental damage leading to increased feto-maternal cell traffic. Alternatively the rate of transfer of fetal cells into the maternal circulation is not altered but in growth restriction the proportion of fetal erythroblasts in fetal blood is increased.     

Fetal motor activity and maternal cortisol

The contemporaneous association between maternal salivary cortisol and fetal motor activity was examined at 32 and 36 weeks gestation. Higher maternal cortisol was positively associated with the amplitude of fetal motor activity at 32 weeks, r(48) = .39, p < .01, and 36 weeks, r(77) = .27, p < .05, and the amount of time fetuses spent moving at 32 weeks during the 50 min observation period, r(48) = 33, p < .05. Observation of periods of unusually intense fetal motor activity were more common in fetuses of women with higher cortisol, Mann–Whitney U = 58.5. There were no sex differences in fetal motor activity, but the associations between maternal cortisol and fetal motor amplitude and overall movement were significantly stronger for male than female fetuses. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 505–512, 2009     

Fetal biometry in the Brachmann-de Lange syndrome

The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established rations of fetal body proportions. The cross-sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of “small for gestational age” would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length ) in 4 of the 11 fetuses where such information could be obtained. BDLS fetuses demonstrate early and symmetric intrauterine growth retardation. We conclude that fetal biometry can provide a valuable index in the assessment of a pregnancy suspected to be at risk for a severely affected BDLS child. © 1993 Wiley-Liss, Inc.     

Comparison of alterations in fetal regional arterial vascular resistance in appropriate-for-gestational-age singleton, twin and triplet pregnancies.

The objective of this longitudinal study was to evaluate alterations in fetal vascular resistance of fetal peripheral arteries with advancing gestation in singleton appropriate-for-gestational-age (S-AGA), twin appropriate-for-gestational-age (Tw-AGA) and triplet appropriate-for-gestational-age (Tri-AGA) infants. Colour Doppler flow imaging and pulsed Doppler ultrasonographic examinations were performed on 35 S-AGA, 52 Tw-AGA and 12 Tri-AGA fetuses. The pulsatility index for middle cerebral artery (MCAPI), umbilical artery (UAPI), descending aorta (DAPI), splenic artery (SAPI), renal artery (RAPI) and femoral artery (FAPI) was measured as vascular resistance every 2 weeks after 15 weeks of menstrual age until delivery. Optimal models and normal ranges for pulsatility index for each artery in each group were generated. The alterations in various fetal regional arterial pulsatility indices with advancing gestational age showed no significant differences in S-AGA, Tw-AGA and Tri-AGA infants, respectively. These results suggest that there is no significant difference for regional arterial vascular resistance in AGA fetuses among singleton, twin, and triplet pregnancies, whereas there was a slight difference in fetal growth pattern among singleton, twin, and triplet pregnancies described in our previous investigation.     

Maternal obesity and the developmental programming of hypertension: a role for leptin

Mother–child cohort studies have established that both pre‐pregnancy body mass index (BMI) and gestational weight gain are independently associated with cardio‐metabolic risk factors in young adult offspring, including systolic and diastolic blood pressure. Animal models in sheep and non‐human primates provide further evidence for the influence of maternal obesity on offspring cardiovascular function, whilst recent studies in rodents suggest that perinatal exposure to the metabolic milieu of maternal obesity may permanently change the central regulatory pathways involved in blood pressure regulation. Leptin plays an important role in the central control of appetite, is also involved in activation of efferent sympathetic pathways to both thermogenic and non‐thermogenic tissues, such as the kidney, and is therefore implicated in obesity‐related hypertension. Leptin is also thought to have a neurotrophic role in the development of the hypothalamus, and altered neonatal leptin profiles secondary to maternal obesity are associated with permanently altered hypothalamic structure and function. In rodent studies, maternal obesity confers persistent sympathoexcitatory hyper‐responsiveness and hypertension acquired in the early stages of development. Experimental neonatal hyperleptinaemia in naive rat pups provides further evidence of heightened sympathetic tone and proof of principle that hyperleptinaemia during a critical window of hypothalamic development may directly lead to adulthood hypertension. Insight from these animal models raises the possibility that early‐life exposure to leptin in humans may lead to early onset essential hypertension. Ongoing mother–child cohort and intervention studies in obese pregnant women provide a unique opportunity to address associations between maternal obesity and offspring cardiovascular function. The goal of the review is to highlight the potential importance of leptin in the developmental programming of hypertension in obese pregnancy.     

Role of Placenta in the Regulation of Fetal Erythropoiesis

We studied erythropoiesis in newborn infants delivered by mothers with normal pregnancy and gestosis. The effects of placental extracts on hemopoiesis in JCR mice were also evaluated. Our results suggest that the placenta is involved in the regulation of fetal erythropoiesis. The placenta activates fetal erythropoiesis during physiological pregnancy, while in pregnant women with gestosis the erythropoiesis-stimulating effect of placentas was less pronounced, which probably determines low reticulocyte content in the umbilical blood.     

Sleep restriction during pregnancy: hypertension and renal abnormalities in young offspring rats

Study Objectives:

Because the maternal environment can affect several physiological functions of the newborn, the aim of the present study was to examine the impact of sleep restriction during pregnancy on renal morphology and function in young offspring.

Design:

Female 3-month-old Wistar rats were divided in 2 experimental groups: C (control) and SR (sleep restriction between the 14th and 20th day of pregnancy). Pregnancy was confirmed by vaginal smear. SR females were subjected to sleep restriction by the multiple platform technique for 20 h daily. After birth, only male litters (6 for each mother) were selected and designated OC (offspring from C) and OSR (offspring from SR). At 2 months of age, blood pressure (BP) was measured by tail plethysmography; at 3 months the renal plasma flow (RPF), glomerular filtration rate (GFR), glomerular area, and number of glomeruli per mm³ were evaluated.

Measurements and Results:

Offspring from SR had higher systolic blood pressure than OC. In this group (OSR), we also observed significant increase in RPF and GFR, enlarged glomeruli diameter, and reduced number of glomeruli per mm³ of renal tissue.

Conclusions:

Our data suggest that sleep restriction during pregnancy is able to modify renal development, resulting in morphologic and functional alterations in young offspring.

Citation:

Thomal JT; Palma BD; Ponzio BF; Franco MCP; Zaladek-Gil F; Fortes ZB; Tufik S; Gomes GN. Sleep restriction during pregnancy: hypertension and renal abnormalities in young offspring rats. SLEEP 2010;33(10):1357-1362.     

Tracking evoked responses to auditory and visual stimuli in fetuses exposed to maternal high‐risk conditions

Magnetoencephalography (MEG) has been successfully applied to record fetal auditory (auditory evoked response [AER]) and visual evoked responses (VER). In this study, we report the AER and VER development trajectory by tracking the evoked response detectability and latency from recordings starting at 27 weeks of gestation in pregnancies classified as high risk. Fetal MEG and ultrasound recordings were performed on 158 pregnant women, and the total number of fetal auditory and visual tests conducted was 321 and 237, respectively. The overall evoked response analysis showed 237 AER (73.8%) and 164 VER detections (69.2%). The mean AER latency was 290.7 (SD 125.5) ms and the mean VER latency was 293.7 (SD 114.5) ms. The rate of decrease (95% confidence limits) in average AER and VER first‐peak latency between 100–350 ms was 1.97 (?1.86, +5.81) ms/week and 1.35 (?3.83, +6.53) ms/week, respectively. This trend in high‐risk fetuses conforms to the general trajectory of decrease in latency with gestational age progression, even though this decrease was non‐significant, as reported in the case of normal growing fetuses. Although there was a significant difference in detection rates between male and female fetuses, this was not reflected in either latency values or the sensory modality applied. Furthermore, the main factors that had the most significant effect on response detectability included the presence of intervening layers of adipose tissue between the fetal head and stimulus source and an increase in the maternal body mass index.     

Fetal cells participate over time in the response to specific types of murine maternal hepatic injury

BACKGROUND: In humans, fetal microchimeric cells transferred to maternal tissues during pregnancy can adopt a hepatocyte phenotype. Our objective was to determine whether fetal cells participate in the response to specific murine post-partum hepatic injuries. METHODS: Wild-type female mice were bred to males transgenic for the enhanced green fluorescent protein (GFP) (n = 42). Following delivery, we created models of chemical or surgical injury with carbon tetrachloride (CCl(4)) injection or by performing partial hepatectomy. Liver injury was assessed histologically. Fetal cells in maternal liver were detected and measured by real-time PCR amplification of the gfp transgene and by immunofluorescence using anti-GFP antibodies. RESULTS: PCR results showed that in chemical but not surgical injury, fetal GFP+ cells were detectable in maternal liver and spleen and that fetal cell presence was significantly increased over time following injury (4 versus 8 weeks, P = 0.006 for liver and P = 0.0006 for spleen). In some animals, following chemical injury, GFP+ cells were detected by immunofluorescence. CONCLUSIONS: The results of this preliminary study suggest that specific types of injury may elicit different fetal cell responses in maternal organs. There is a significant effect of time on fetal cell presence in liver and spleen. Furthermore, real-time PCR amplification is more sensitive than immunofluorescence for the detection of microchimeric fetal cells.     

Altered transmission of maternal angiotensin II receptor haplotypes in fetal growth restriction

Fetal growth restriction (FGR) predisposes to significant short- and long-term health problems. Epidemiological studies have suggested a role for inherited factors in its pathogenesis. The angiotensin II receptor genes, AGTR1 and AGTR2, are candidate genes because they mediate processes that are important for placentation. This study investigated AGTR1 and AGTR2 haplotypes and genotypes in FGR. A total of 107 families (father, mother, and baby) with FGR, and 101 families with normal pregnancies were genotyped at five sites in AGTR1 and six sites across AGTR2. All of the participants were white western Europeans. FGR was identified antenatally by ultrasound scans and confirmed postnatally by correcting the birth weight centile for gestation, infant sex, maternal height, weight, and parity. Fetal genes were investigated using transmission disequilibrium testing (TDT), and a case-control comparison of maternal haplotypes was conducted. FGR was associated with maternal (but not paternal) transmission of the AGTR1 haplotype (GenBank AF245699.1) g.4955T, g.5052T, g.5245C, g.5612A, and haplotype g.4955T, g.5052T, g.5245T, g.5612A. Haplotype g.4955A, g.5052G, g.5245T, g.5612G was undertransmitted (P = 0.002). TDT of the AGTR1 genotype showed undertransmission of maternal AGTR1 genotypes g.4955T>A (odds ratio (OR), 0.34 (95% confidence interval (CI), 0.14-0.86); P = 0.02), g.5052T>G (OR, 0.18 (0.06-0.48); P<0.001), and g.5612A>G (OR, 0.21 (0.08-0.55); P < 0.001) in FGR. There were no differences in maternal haplotype frequencies between normal pregnancy and FGR for AGTR1 or AGTR2 (P > 0.10). This is the first study to show distortion of transmission of maternal AGTR1 haplotypes in FGR, which suggests that this gene plays a role in FGR. In particular, maternal-fetal gene sharing may be an important factor.     

妊高征合并胎儿发育迟缓患者分娩方式与围产儿预后-20年回顾分析

目的为了探讨妊高征(PIH)合并胎儿宫内发育迟缓(IUGR)患者分娩方式对围产儿预后的影响.方法回顾性分析近20年来在我院分娩的355例PIH合并IUGR患者分娩方式与围产儿预后的关系.结果355例IUGR围产儿,死亡24例(67.6‰),新生儿窒息75例(21.13%).其中阴道分娩组(n=230)围产儿死亡22例(95.7‰),新生儿窒息56例(24.35%);剖宫产组(n=125)围产儿死亡2例(16‰),新生儿窒息19例(15.2%).两组围产儿死亡率差异有显著意义(P=0.008),新生儿窒息率差异无显著意义(P=0.06).剖宫产组中,急诊剖宫产组(n=64)围产儿死亡2例(31.25‰),新生儿窒息15例(23.44%);择期剖宫产组(n=61)国产儿无死亡,新生儿窒息4例(6.56%).两组围产儿死亡率差异无显著意义(P=0.493),新生儿窒息率差异有显著意义(P=0.017).阴道分娩组围产儿死亡的主要原因为胎儿宫内缺氧,而剖宫产组为孕妇严重并发症.结论分娩方式是影响PIH合并IUGR围产儿预后的关键环节.控制PIH病情,减少孕妇并发症,胎儿适时脱离宫内缺氧环境,对改善围产儿预后致关重要.     

孕妇血中胎儿微小RNA等核酸在唐氏综合征无创产前诊断中的应用

唐氏综合征是最常见的染色体非整倍体遗传病,出生干预是预防该病的有效措施.传统的产前诊断具有创伤等缺陷,无创产前诊断是未来发展的需求.孕妇血胎儿细胞、胎儿游离DNA、胎儿游离RNA及胎儿游离microRNA的分析是新近发展的4种唐氏综合征无创产前诊断技术.母血胎儿游离miRNA有足够的稳定性、特异性和准确性,是最具临床应...     

Quantification of all fetal nucleated cells in maternal blood in different cases of aneuploidies

We quantified all fetal nucleated cells (FNCs) per unit volume of maternal blood in different aneuploid pregnancies using molecular cytogenetic techniques. Seven cases of male trisomy 18, two triploidies (69,XXX), two 47,XXX, one 47,XXY, one 47,XYY, one male trisomy 13, and one case of 47,XY,r(22),+r(22) were analyzed. Whole blood samples were obtained from 15 women between 17 and 29 gestational weeks and harvested without using fetal cell enrichment procedures. Fluorescence in situ hybridization and primed in situ labeling were performed to identify the FNCs. All slides were manually scanned to quantify those cells. We have identified 4-20 FNCs/ml of maternal blood in the cases of trisomy 18; 10 and 25 FNCs/ml in the two cases of triploidy; 16 and 14 FNCs/ml, respectively, in the two X trisomies; 19 FNCs/ml in the 47,XXY; 26 FNCs/ml in the 47,XYY; nine FNCs/ml in the trisomy 13; and 10 FNCs/ml in the case of r(22). To detect all FNCs in all aneuploid pregnancies, we have used a very simple method that minimizes the manipulation steps to avoid losing fetal cells. The number of FNCs identified in aneuploid pregnancies was 2-5 times higher than in normal pregnancies. This higher number of FNCs will favor the design of a non-invasive pre-natal test.     

Insulin in obstetrics: a main parameter in the management of pregnancy

Insulin plays a central role in human pregnancy. Maternal insulin sensitivity decreases with advancing gestation in order to provide glucose and possibly other nutrients for feto-placental growth and energy needs. Moreover, alterations of insulin metabolism are clearly involved in the development of gestational diabetes. In recent years, hyperinsulinaemia has been also proposed as a possible pathogenic factor in the development of gestational hypertension and preeclampsia; furthermore it has also been postulated that there is an involvement of insulin sensitivity in fetal growth restriction. These intriguing data have stimulated our interest in summarizing the physiopathological mechanisms by which the pancreatic hormone could be involved in obstetrics.     

The Identification of Suppressor Cells in the Murine Fetal Liver*

ABSTRACT: Fetal suppressor cells are potentially important for maintenance of pregnancy and for the immune regulation of the identification of self. We have identified and partially characterized a population of murine fetal liver cells which are active suppressors of a variety of immune responses, including mixed lymphocyte responses (MLR), responses to mitogens plaque-forming cell responses to heterologous erythrocytes. The suppression is non-H-2-restricted and can act via a factor. The cell is preactivated in fetal liver and may represent a T-cell precursor. The suppression of MLR is maximal (approximately 100%) if cells are added within the first 48 h of culture initiation. The characteristics of this suppressor cell are compared to other known MLR and perinatal suppressor systems.     

Fetal haemodynamics before and after treatment of maternal hypertension in pregnancy

The haemodynamics of fetuses of 15 pregnant women who developed hypertension during the last trimester of pregnancy were investigated before and after antihypertensive treatment using the ultrasound-Doppler method for non-invasive measurements of blood flow, and the results were compared to those from investigations of fetuses from normal pregnancies. In the untreated condition, significant reduction of blood flow was demonstrated in the fetal descending aorta (p less than 0.01) and in the umbilical vein (p less than 0.02). The resistance to flow, expressed as the Pulsatility Index, was significantly elevated (p less than 0.001). A significant correlation was shown between Pulsatility Index and maternal diastolic blood pressure (p less than 0.001) and a significant negative correlation between blood velocity in fetal aorta and maternal diastolic blood pressure (p less than 0.01). Treatment resulted in significant reduction of resistance to flow, which remained normal for the rest of the pregnancy. It is concluded that fetal haemodynamics are affected by maternal hypertension during pregnancy. The results suggest that the fetus also suffers from hypertension. Therapy with oral alpha-methyldopa and labetalol combined with volume expansion with human albumine normalised fetal circulation and kept it normal for the remainder of the pregnancy.