Ultrasound evaluation of the normal fetal pharynx

OBJECTIVE: To obtain normative data for fetal pharyngeal diameter and to investigate the ability to visualize pharynx at different gestational ages during routine prenatal sonography. METHODS: Sonographic studies were performed in 292 consecutive pregnant women. The diameters of the pharynx were measured and our ability to visualize pharynx was evaluated at different gestational ages. RESULTS: Sonographic measurements of the pharyngeal diameter were obtained in 153 of the 292 fetuses. The diameter of the pharynx increased from a mean of 4.5+/-0.53 mm at 16 weeks to 9.1+/-1.72 mm at 36 weeks. Pharyngeal diameters showed a significant positive relationship with advancing gestational age (p<0.0001, R2=0.571). The differences in visualization among different gestational age groups were found to be significant (p<0.05 by Chi-Square). CONCLUSION: This study reports normative data for fetal pharyngeal diameter. Pharyngeal measurements were similar to previous reports in the literature. Our success in visualizing the pharynx was best between 21 and 30 weeks of gestation. This period might be the optimum time for evaluating fetal pharynx.     

Action of polyamines on ribonucleic acid and protein synthesis during ontogeny of human fetal liver

A higher rate of RNA synthesis in human fetal liver cells was found during the early age of gestation, after a drop, it gradually increases to a maximum value between 18 and 22 weeks, followed by a sharp decrease at later period of gestation. Total polyamine content of fetal liver tissue shows a similar trend. However, when liver cell suspension was incubated with exogenous spermine, spermidine and putrescine there is a dose-dependent inhibition in RNA synthesis. Protein synthesis in human fetal liver cells was stimulated with lower doses of spermine, spermidine and putrescine and inhibited at higher doses. The optimum dose for stimulation and the degree of stimulation was, however, not the same for fetuses of different gestational ages.     

Thymidine factor in human cord sera and relationship to birth size, gestational age and insulin

Thymidine factor was studied in human cord sera from 44 neonates with gestational ages ranging between 36 and 43 weeks. Thymidine factor was determined by the uptake of 6-3H-thymidine using isolated chick embryo cartilage cells. The thymidine factors increased with gestational age and those of neonates at 40 weeks of gestation were 0.89 +/- 0.17 U/ml (mean +/- SD), but were significantly lower after 42 weeks of gestation. There was no correlation between thymidine factor in cord sera and birth weight or size. There was a positive correlation (p less than 0.02) between insulin level and thymidine factor in cord sera. Our data suggest that somatomedin measured as thymidine factor might not have a major role in fetal growth and insulin might be an important factor in the synthesis of somatomedin by the fetus.     

New birthweight and head circumference centiles for gestational ages 24 to 42 weeks

Based on 20,713 singleton livebirths at the John Radcliffe Hospital, Oxford, in 1978-1984, we calculated new birthweight and head circumference values for males and females between 24 and 42 weeks of gestation. Among the 803 babies born at or before 34 weeks of gestation, 28% were delivered electively for fetal problems; they were considerably lighter and had smaller heads than infants born after spontaneous preterm labour. As we and others have recommended elsewhere, the electively delivered preterm infants were excluded from the calculation of the new birthweight and head circumference centiles. In our series males were heavier and had larger head circumferences than females at most gestational ages. There were consistent and statistically significant differences in birthweight at all gestational ages from 37 weeks and in head circumference at all gestational ages from 35 weeks.     

DEVELOPMENT OF THE HUMAN FETAL TESTIS

We describe the histological features of the fetal testis, utilizing 68 fetuses ranging in gestational age from 10 to 41 weeks. During fetal life, the tunica albuginea progressively increases in thickness, and between 29 and 32 weeks it develops two layers. Beyond 25 to 28 weeks, septa are invariably present. Tubules begin as straight structures and become maximally coiled by 30 weeks. Tubular diameter reaches its maximum by 16 weeks and remains constant throughout the rest of gestation. Germ cell and Sertoli cell numbers per tubular diameter have a wide range, but the median number for each cell type remains constant after 13 to 16 weeks. Leydig cells are most numerous between 17 and 19 weeks and decline thereafter. They are infrequent but still present at term. Interstitial lipochrome pigment accumulates during the latter half of gestation and may represent breakdown products from Leydig cell degeneration.     

RENAL FUNCTION AS A MARKER OF HUMAN FETAL MATURATION

Abstract. Sixty clinically well infants of various gestational ages (27 to 40 weeks) were studied from 24–40 hours after birth to evaluate glomerular filtration rate and renal excretion rate of sodium at various stages of fetal maturation. Creatinine clearance was directly related to gestational age ( r =0.643). Fractional sodium excretion was inversely related to gestational age ( r =-0.755). The renal functions of small for gestational age infants were similar to those of full-term infants whose birth weights were appropriate for gestational age. The data showed that the glomerular functions of an infant below 32 weeks of gestation were more predominant than the tubular function resulting in a greater fractional sodium excretion rate and higher urinary Na loss in infants of this gestational age, when compared with the more mature infants.     

Maternal clofibrate administration amplifies fetal peroxisomes

To study the effects of peroxisome proliferators on fetal biogenesis, 400 mg/kg oral clofibrate was administered to pregnant mice beginning at d 6 of gestation. Maternal/fetal tissues from three separate experiments were harvested between gestational d 13 and 19 and maternal/fetal tissues were assayed for peroxisomal matrix, membrane-associated, and integral membrane proteins. By comparison to control pregnancies that received vehicle only, clofibrate produced a 4- to 5-fold increase in the levels of peroxisomal membrane protein 70, a 1.5- to 2-fold increase of dihydroxyacetone phosphate acyltransferase (DHAP-AT) sp act, and a 1.2- to 1.8-fold increase of catalase sp act in fetal liver of 19 d gestation. Fetal liver endoplasmic reticulum and peroxisomes were also amplified as visualized by electron microscopy. Clofibrate exhibited maximal effects on maternal tissues by 6 d of oral treatment with increases in peroxisomal membrane protein 70 occurring most clearly in maternal liver; DHAP-AT activity was increased in maternal liver, kidney, and brain but not in lung. Slight increases in DHAP-AT activities were evident in fetal brain, lung, and placenta as compared with the greater increases in liver and kidney. There was a general increase in peroxisomal proteins between 13 and 19 gestational d in all fetal tissues except placenta, and the effect of clofibrate was evident by gestational d 13 in lung and placenta. Minimal changes in the activities of acid phosphatase (lysosomal enzyme) or glycerol-3-phosphate acyltransferase (microsomal enzyme) were observed in maternal or fetal tissues although the latter enzyme was increased 10-30% by clofibrate in maternal brain, fetal lung, and placenta.(ABSTRACT TRUNCATED AT 250 WORDS)     

人胎脑室下区发育过程中神经干细胞的变化

目的观察人胎脑室下区不同发育时期神经干细胞(NSCs)的变化,为调控自身NSCs治疗神经系统退行性疾病提供实验依据。方法收集胎龄24~28周的水囊引产胎儿30例,采用原位杂交及光镜技术对其脑室下区NSCs的分布、形态以及生长方式进行检测。结果不同胎龄人胎脑室下区均可见Nestin mRNA表达阳性NSCs,NSCs呈星形,有3~6个突起,多个突起形成网丛,细胞散在分布在网丛中,胞核呈圆形,1~4个核仁,细胞染色质疏松。多数NSCs单个存在,可见对称分裂的NestinmRNA表达阳性NSCs和3个NSCs形成的集落样生长方式。不同胎龄Nestin mRNA表达阳性NSCs的分布部位、细胞形态无明显区别,但Nestin mRNA表达阳性NSCs生长方式上存在一定差异。结论不同胎龄人胎脑室下区均存在NSCs,NSCs生长方式随胎龄不同而变化,调控在体NSCs有望成为治疗儿童神经退行性疾病的另一种有效方法。     

Development of the pons in human fetuses

Morphometric and histological studies of the pons were performed by light microscopy in 28 cases of externally normal human fetuses ranging from 90 to 246 mm in crown-rump length (CRL) and from 13 to 28 weeks of gestation. The brainstems of fetuses were embedded in celloidin or paraffin, and transverse sections were prepared. The pons was divided into two regions at the most ventral margin of the medial lemniscus at the level of the motor trigeminal nucleus. The relationships between the total dorsoventral length, ventral length, and dorsal length of the pons versus CRL and gestational ages were calculated, and empiric formulas were fitted. It was found that the ventral portion increased in size more rapidly than the dorsal portion. The proportion of the ventral portion in the total dorsoventral length was constitutively higher than that of the dorsal portion in the present range of CRL. In the pontine nuclei, from 235 mm in the CRL, some large cells with rich cytoplasm, pale nuclei, and a distinct nucleolus appeared on the dorsal side of the pyramidal tract. According to Weigert stained preparations, the first myelinated fibers in each motor root of the trigeminal, abducent, and facial nerves were recognized at 130-140 mm in CRL and the medial lemniscus at 230-235 mm.     

Survival of very preterm infants: Epipage, a population based cohort study

OBJECTIVE: To evaluate the outcome for all infants born before 33 weeks gestation until discharge from hospital. DESIGN: A prospective observational population based study. SETTING: Nine regions of France in 1997. PATIENTS: All births or late terminations of pregnancy for fetal or maternal reasons between 22 and 32 weeks gestation. MAIN OUTCOME MEASURE: Life status: stillbirth, live birth, death in delivery room, death in intensive care, decision to limit intensive care, survival to discharge. RESULTS: A total of 722 late terminations, 772 stillbirths, and 2901 live births were recorded. The incidence of very preterm births was 1.3 per 100 live births and stillbirths. The survival rate for births between 22 and 32 weeks was 67% of all births (including stillbirths), 85% of live births, and 89% of infants admitted to neonatal intensive care units. Survival increased with gestational age: 31% of all infants born alive at 24 weeks survived to discharge, 78% at 28 weeks, and 97% at 32 weeks. Survival among live births was lower for small for gestational age infants, multiple births, and boys. Overall, 50% of deaths after birth followed decisions to withhold or withdraw intensive care: 66% of deaths in the delivery room, decreasing with increasing gestational age; 44% of deaths in the neonatal intensive care unit, with little variation with gestational age. CONCLUSION: Among very preterm babies, chances of survival varies greatly according to the length of gestation. At all gestational ages, a large proportion of deaths are associated with a decision to limit intensive care.     

Longitudinal measurements of fetal heart rate (FHR) monitoring in second trimester.

We investigated the possibility of clinical diagnosis of preterm fetal well-being in the second trimester using the duration of LTVs of less than 4.5 beats/min and characteristic FHR acceleration. Fetuses between 24 and 32 weeks gestation, unlike near-term fetuses are seldom quiet and therefore the prolonged absence of fetal movement may be the best indicator of a sick fetus at these gestational ages. The amplitude and duration of the acceleration of the FHR were also clinically useful diagnostic tools for fetus well-being during the second trimester.     

Effects of maternal glucose ingestion on human fetal breathing movements at weeks 24 and 28 of gestation

The incidence of human fetal breathing movements was studied in normal pregnancies before and after administration of 50 g glucose or a placebo (water) at 24 and 28 weeks. Glucose or water was given to the same women on two separate days in a randomised order. No significant differences were present among the results on the placebo-day and the control period of the glucose-day at either gestational age. On the glucose-day, the incidence rose significantly from 3.6 to a maximum of 11.6% at 24 weeks, and from 6.7 to 30.2% at 28 weeks. At both ages the maximum was found 90-120 min after the intake of glucose. It is concluded that already at 24 weeks gestation the human fetus reacts with an increase of fetal breathing movements after the administration of glucose to the mother.     

Growth of the adrenal gland of the normal human fetus during early gestation

The weights of 182 adrenal glands obtained from presumably normal human fetuses delivered by elective abortion between 6 and 17 weeks post-conceptional gestational age were measured. There was little increase in adrenal weight between 6 and 12 weeks gestation. Thereafter, the rate of increase in adrenal weight was rapid. There were no significant differences between the adrenal gland of male and female abortuses of similar gestational ages.     

TRANSEPIDERMAL WATER LOSS IN NEWBORN INFANTS

Abstract. Using a method described earlier, the evaporation rate (ER) was studied at different humidities in 12 newborn infants born after 25 to 30 weeks of gestation and 10 infants born after 32 to 35 weeks. Transepidermal water loss (TEWL) was estimated in 32 infants born after 25 to 39 weeks of gestation. The ER values were highest in the infants with the lowest gestational age and the susceptibility to changes in ambient humidity was also greater at lower gestational ages. An exponential relationship was found between TEWL and gestational age, TEWL being 15 times higher in infants born after 25 weeks of gestation than in full-term infants.     

Essential fatty acid status during early human development.

Preliminary studies indicated that the EFA status of normal neonates is marginal, if not insufficient. Since a better knowledge of the physiology of maternal-fetal essential fatty acid transfer is relevant for nutritional recommendations during pregnancy, we investigated the course of the fetal EFA status during fetal development by analysing the absolute (micrograms/g dry fetal tissue) and relative (% of total fatty acids) fatty acid composition of phospholipids in human fetal tissue, (n = 40, gestational age 5-15.2 weeks). The total content of fatty acids (mg/g dry fetal tissue) increased with gestational age. The absolute amount of virtually all fatty acids increased with maturation. Linoleic acid (18:2n-6, LA), however, was an exception. A highly significant, negative correlation between gestational age and the relative amount of LA in fetal tissue was observed during this first trimester of pregnancy. Our results show that the fetal-maternal difference in linoleic acid content observed at birth, initiates early in pregnancy. Since the fetus completely depends on the mother for its EFA supply, the maternal EFA status was measured simultaneously by analysing the fatty acid composition of phospholipids, isolated from plasma and red blood cells. Significant positive correlations between maternal rbc and fetal tissue were found for the relative amounts of LA. Similar relationships were observed between maternal plasma and fetal tissue for the relative amounts of cervonic acid (22:6n-3), the most abundant essential fatty acid in brain and retina. The relation between maternal and fetal EFA in phospholipids is significantly more pronounced after 10 weeks of gestation than before. This might be connected with the increased importance of the placenta with respect to maternal-fetal fatty acid transfer after 10 weeks of gestation.     

Basal and meal-stimulated pepsinogen secretion in preterm infants: a longitudinal study.

In order to establish longitudinal normal values for basal and meal-stimulated pepsinogen secretory function in preterm infants, we studied 44 preterm infants with gestational ages of 28-36 weeks during the period of nasogastric tube feeding. Three age groups were evaluated: gestational ages of 28-30, 31-33, and 34-36 weeks. Basal pepsinogen did not change with postnatal age in any of the groups. Significant meal-stimulated pepsinogen secretion appeared during the third postnatal week in infants of 28-30 weeks of gestation. In the groups of infants of 31-33 and 34-36 weeks of gestation, significant meal-stimulated pepsinogen secretion was apparent in the first postnatal week. This study suggests that maturation of pepsinogen secretion appears at 31 weeks of gestation, independent of early feeding.     

Low Apgar score and mortality in extremely preterm neonates born in the United States

Aim: To investigate the relationship between low Apgar score and neonatal mortality in preterm neonates. Methods: Infant birth and death certificate data from the US National Center for Health Statistics for 2001–2002 were analysed. Primary outcome was 28‐day mortality for 690 933 neonates at gestational ages 24–36 weeks. Mortality rates were calculated for each combination of gestational age and 5‐min Apgar score. Relative risks of mortality, by high vs. low Apgar score, were calculated for each age. Results: Distribution of Apgar scores depended on gestational age, the youngest gestational ages having higher proportions of low Apgar scores. Median Apgar score ranged from 6 at 24 weeks, to 9 at 30–36 weeks gestation. The relative risk of death was significantly higher at Apgar scores 0–3 vs. 7–10, including at the youngest gestational ages, ranging from 3.1 (95% confidence interval 2.9, 3.4) at 24 weeks to 18.5 (95% confidence interval 15.7, 21.8) at 28 weeks. Conclusion: Low Apgar score was associated with increased mortality in premature neonates, including those at 24–28 weeks gestational age, and may be a useful tool for clinicians in assessing prognosis and for researchers as a risk prediction variable.     

Immunophenotypic changes of fetal cord blood hematopoietic progenitor cells during gestation

We measured cell surface expression of CD34, HLA-DR, CD38, CD19, CD33, CD71, and CD45 antigens in the hematopoietic progenitor cells of fetal cord blood to investigate immunophenotypic changes at different gestational ages. These antigens were identified by flow cytometry in 11 fetuses (gestational age 19-24 wk, in 12 preterm (25-28 wk) and in ten newborn infants born at term. The frequency and number of CD34+ cells were higher in the blood of the 11 fetuses; in addition, a statistically significant inverse correlation between number of CD34+ cells and advancing gestational age was noted. The numbers of CD34+ CD19+, CD34+ CD33+, and CD34+ CD45+ coexpressing cells were significantly higher in the fetuses, whereas CD34+ CD38+ cells were more represented in the neonates at term. Gestational age was inversely correlated with the number of CD34+ CD19+ and CD34+ CD33+ coexpressing cells. A positive correlation between gestational age and CD34+ CD38+ cells was noted. The number of CD34- CD19+, CD34- CD38+, and CD34- CD45+ cells was higher in term infants; furthermore, a significant correlation between advancing gestational age and CD34- CD38+ or CD34- CD45+ cells was demonstrated. The proliferative capacity was also higher at lower gestational ages. These data suggest that the development and lineage commitment of fetal cord blood hematopoietic progenitor cells are very active during the last two trimesters of pregnancy. The most significant changes of hematopoietic cells maturation seem to occur within 25 wk of gestation.     

EGF- and TGF-alpha-like peptides in human fetal gut

The presence of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) immunoreactivities in fetal human tissues was studied immunohistochemically at different gestational ages. EGF and TGF alpha immunoreactivities were detected from the 20th gestational wk. EGF immunoreactivity was limited to the small intestine, but TGF alpha immunoreactive cells were present in the colon also. According to radioreceptor assay, the intestine of a 19-wk-old human fetus contained 10 times more EGF receptor-binding substance than EGF, as measured by immunofluorometric assay. Chromatographic analysis suggests that TGF alpha-like peptides account for at least part of this activity, as so argues in favor of the presence of TGF alpha- and EGF-like peptides in the human fetal gut. Whether they are synthesized in the fetus is yet unknown.     

Risk factors for unexplained antepartum fetal death in Norway 1967-1998

OBJECTIVE: To relate unexplained antepartum fetal death with maternal and fetal characteristics in order to identify risk factors. DESIGN: Population-based study based on records of 1,676,160 singleton births with gestational age > or =28 weeks. Unexplained antepartum fetal death was defined as fetal death before labour without known fetal, placental, or maternal pathology. RESULTS: Although unexplained fetal mortality in general declined from 2.4 per 1000 births in 1967-1976 to 1.6 in 1977-1998, the proportion among all fetal deaths increased from 30% to 43% during the same period of observation. Unexplained fetal death occurred later in gestation than explained. From 39 weeks of gestation, the risk increased progressively to 50/10,000 in women aged > or =35 years and <10/10,000 in women <25 years. In birth order > or =5, the risk was particularly high after 39 weeks of gestation. For birth weight percentile 2.5-9.9 and > or =97.5, unexplained fetal death was four and three times more likely to occur, respectively. We found an additive effect of maternal age and birth weight percentile 2.5-9.9. Women with less than 10 years education had higher risk than women with 13 years or more (OR=1.6). Weaker associations were observed with female gender, unmarried mothers, and winter season. CONCLUSIONS: Unexplained antepartum fetal death occurred later in gestation than explained and was associated with high maternal age, multiparity, low education, and moderately low and high birth weight percentile. The increased risk in post-term pregnancies and the additive effect of maternal age and birth weight percentile 2.5-9.9 suggests that older women would benefit from monitoring of fetal growth.