A study of human foot length growth in the early fetal period.

The length of the human fetal foot was studied in 106 feet from 53 unfixed staged human fetuses (35 males and 18 females) by means of the allometric formula log Y = log b+k log X. The gestational age ranged from 13 to 26 weeks postconception. The measurement taken from the heel to the tip of the longest toe was regarded here as the maximum length of the foot. Growth in length of the foot was analysed in relation to crown-rump length. Our results show that foot length growth is correlated to crown-rump growth and is allometrically positive. No statistically significant difference was found between right and left feet or between male and female fetuses.     

The distribution of fetal nuchal translucency thickness in normal Korean fetuses

The aim of present study was to establish normative data for the distribution of nuchal translucency (NT) thickness in normal Korean fetuses. The data were collected from pregnant women with singleton pregnancies in whom fetal ultrasound was performed and the fetal NT thickness was measured between 11 and 14 weeks of gestation. Among them, a total of 2,577 fetuses with a known normal outcome were included in this study. The distribution of multiple of median (MoM) values of the NT thickness with crown-rump length (CRL) in 10-mm intervals and the 95th percentile of MoM were calculated with the linear regression method. The present study showed that NT measurements increase with increasing CRL and a false positive rate increases with increasing gestational age. Therefore, a fixed cut-off point through the first trimester was not appropriate and each NT measurement should be examined according to the gestational age. The present study offers normative data of the fetal NT thickness in a Korean population, which can be used as reference for screening chromosomal aberrations or other congenital abnormalities in the first trimester.     

胎儿孤立性单侧侧脑室扩张对脑实质体积影响的MRI研究

目的 研究不同程度单侧侧脑室扩张对脑实质体积的影响并探讨其对胎儿诊疗的临床价值。方法 收集经超声证实的孤立性单侧侧脑室扩张的胎儿,行胎儿颅脑1.5T MR扫描。测量扩张侧及正常侧的侧脑室宽度、相邻外侧脑实质厚度、侧脑室体积、大脑半球体积,并计算脑实质体积。每隔1月随访侧脑室宽度随孕周的变化情况。结果 最终纳入研究的23～31孕周的孤立性单侧侧脑室扩张胎儿共49例,按扩张程度分为3组：轻度扩张组12例、中度扩张组27例、重度扩张组10例。对比研究结果如下：(1) 3组病例的扩张侧与正常侧比较,扩张侧邻近脑实质厚度减小,脑实质体积未见明显差异;(2) 3组病例间的扩张侧侧脑室宽度、体积及大脑半球体积均存在差异（P<0.05）,扩张侧脑实质厚度及体积未见明显差异;(3)随访发现轻中度扩张组侧脑室宽度逐渐减小者占76%,重度扩张组流产率达80%。结论孤立性单侧侧脑室扩张对脑实质的体积没有影响,轻中度扩张胎儿预后好,这为侧脑室扩张胎儿的评估、预后和干预提供了重要影像学信息。     

Skeletal malformations in fetuses with Meckel syndrome.

In six fetuses with Meckel syndrome (gestational age 16-23 weeks, crown-rump length 130-170 mm) the skeleton was examined as part of the autopsy procedure using whole body radiography and special radiographic techniques. In the upper and lower limbs we found similar types of polydactyly. We noted four types, based on the number and morphology of metacarpals and metatarsals. In the individual fetus there was more often similarity in the pattern of malformation in the two hands or in the two feet than there was between the pattern of malformation seen in the hands and that seen in the feet. Only one foot was normal. Malformations of the cranial base (the basilar part of the occipital bone or the postsphenoid bone) occurred in five cases, and the vertebral bodies in the lumbar region of the spine were malformed (cleft) in three cases. It is proposed that a skeletal analysis be included in the future evaluation of phenotypes in Meckel syndrome.     

Fetal growth from 12 to 26 weeks of gestation

175 freshly aborted fetuses (including three pairs of twins), 12-26 weeks postmenstrual age and products of induced expulsion from 172 Kashmiri women, were observed for 12 anthropometric measurements, namely, crown-heel length, crown-rump length, trunk height, head length, head circumference upper-arm length, fore-arm length, hand length, thigh length, leg length, foot length and weight. The general pattern of age changes in various body dimensions conforms to the sigmoid nature of human fetal growth. Comparison of the present findings with those from other studies reveals no definite population trends. The mean values for various anthropometric variables of Kashmiri fetuses lie within the overall range of observations made by various authors.     

Fetal growth from 12 to 26 weeks of gestation

175 freshly aborted fetuses (including three pairs of twins), 12–26 weeks postmenstrual age and products of induced expulsion from 172 Kashmiri women, were observed for 12 anthropometric measurements, namely, crown-heel length, crown-rump length, trunk height, head length, head circumference upper-arm length, fore-arm length, hand length, thigh length, leg length, foot length and weight.

The general pattern of age changes in various body dimensions conforms to the sigmoid nature of human fetal growth. Comparison of the present findings with those from other studies reveals no definite population trends. The mean values for various anthropometric variables of Kashmiri fetuses lie within the overall range of observations made by various authors.     

The role of perinatal autopsy in the management of pregnancies with major fetal trisomies

We assessed the value of perinatal autopsy following mid-trimester termination of pregnancy due to major fetal trisomies. Singleton fetuses (n=305) that underwent prenatal sonography and karyotyping during the second trimester of pregnancy and that had trisomy 21, trisomy 18, or trisomy 13 constituted the study population. The findings of second trimester sonography and fetal autopsy were compared. Altogether, 611 separate major structural malformations were diagnosed during autopsy. Full agreement was achieved between sonography and autopsy in 35.8% of the malformations. The additional findings at autopsy (64.2%) involved mainly two organ systems: face, including ears and eyes, and extremities, including hands and feet. Some ultrasound findings were not confirmed at autopsy (n=49). Concordance rates between sonography and autopsy findings regarding soft markers were considerably high in cases of increased nuchal fold thickness and short femur/humerus. On the other hand, fetal autopsy was of limited value as far as hyperechoic bowel and echogenic intracardiac foci are concerned. Pathologic examination provides additional information regarding many fetuses with aneuploidy, and may indicate possible directions of sonographic screening for major chromosome aberrations. However, prenatal sonography and perinatal autopsy should be considered as complementary ways of increasing our knowledge about the possible features of fetal aneuploidies.     

Skeletal malformations in fetuses with Meckel syndrome

In six fetuses with Meckel syndrome (gestational age 16–23 weeks, crown-rump length 130–170 mm) the skeleton was examined as part of the autopsy procedure using whole body radiography and special radiographic techniques. In the upper and lower limbs we found similar types of polydactyly. We noted four types, based on the number and morphology of metacarpals and metatarsals. In the individual fetus there was more often similarity in the pattern of malformation in the two hands or in the two feet than there was between the pattern of malformation seen in the hands and that seen in the feet. Only one foot was normal. Malformations of the cranial base (the basilar part of the occipital bone or the postsphenoid bone) occurred in five cases, and the vertebral bodies in the lumbar region of the spine were malformed (cleft) in three cases. It is proposed that a skeletal analysis be included in the future evaluation of phenotypes in Meckel syndrome. Am. J. Med. Genet. 84:469–475, 1999. © 1999 Wiley-Liss, Inc.     

Clinically diverse and perinatally lethal syndromes with urorectal septum malformation sequence

Urorectal septum malformation sequence (URSMS) is characterized by a spectrum of anomalies of the urogenital system, hindgut and perineum. It is presumed to be a constellation of an embryonic defect. Herein, we analyzed the clinically diverse syndromes associated with URSMS in our perinatal evaluation unit. We reviewed fetuses with URSMS in referrals for perinatal autopsy over a period of 3 years. Chromosomal microarray and genome sequencing were performed whenever feasible. Literature was reviewed for syndromes or malformations with URSMS. We ascertained URSMS in 12 of the 215 (5%) fetuses. Nine fetuses (75%) had complete URSMS and remainder had partial/intermediate URSMS. Eleven fetuses had malformations of other systems that included: cerebral ventriculomegaly; right aortic arch with double outlet right ventricle; microcephaly with fetal akinesia deformation sequence; ventricular septal defect and radial ray anomaly; thoraco-abdominoschisis and limb defects; myelomeningocele; spina bifida and fused iliac bones; omphalocele; occipital encephalocele; lower limb amelia and cleft foot. We report on six fetuses with recurrent and five fetuses with unique malformations/patterns where URSMS is a component. Exome sequencing (one family) and genome sequencing (eight families) were performed and were nondiagnostic. Additionally, we review the literature for genetic basis of this condition. URMS is a clinically heterogeneous condition and is a component of several multiple malformation syndromes. We describe several unique and recurrent malformations associated with URSMS.     

Extracellular glutamate levels and neuropathology in cerebral white matter following repeated umbilical cord occlusion in the near term fetal sheep

Umbilical cord occlusion causes fetal hypoxemia which can result in brain injury including damage to cerebral white matter. Excessive glutamate release may be involved in the damage process. This study examined the relation between extracellular glutamate levels in the cerebral white matter of the ovine fetus during and after intermittent umbilical cord occlusion and the degree of resultant fetal brain injury. Fetal sheep underwent surgery for chronic catheterisation and implantation of an intra-cerebral microdialysis probe at 130 days of gestation (term approximately 147 days). Four days after surgery (day 1), seven fetuses were subjected to 5x2 min umbilical cord occlusions, and on the following day (day 2) they were subjected to either 4 or 5x4 min umbilical cord occlusions; seven fetuses served as controls. Microdialysis samples were collected before, during and after the umbilical cord occlusions to determine extracellular glutamate levels in the cerebral white matter. Fetal blood gas status was measured and the fetal electrocorticogram was recorded continuously. During the periods of umbilical cord occlusions on both days 1 and 2, fetal arterial oxygen saturation, arterial partial pressure of oxygen and arterial pH decreased (P<0.05) while arterial partial pressure of carbon dioxide increased (P<0.05). All fetuses showed episodes of isoelectric electrocortical activity during umbilical cord occlusions on both days 1 and 2. In fetuses with patent microdialysis probes there were marked increases of glutamate efflux in the cerebral white matter following umbilical cord occlusion. Fetal brains were removed at autopsy on day 5 and subjected to histological assessment. Brain damage was observed in all fetuses exposed to cord occlusion, particularly in the periventricular white matter, with the most extensive damage occurring in the fetuses with the greatest increases in glutamate levels. We conclude that, in the unanesthetised fetus in utero, glutamatergic processes are associated with umbilical cord occlusion-induced brain damage in the cerebral white matter.     

The growth of the upper and lower extremities of Turkish fetuses during the fetal period

Prenatal analysis of the fetal structures gives us information about fetal growth and gestational age. The aim of this study was to investigate the morphologic structure of the upper and lower extremities of Turkish fetuses during the fetal period, to measure the morphometric values, and to determine the relationship between CRL (crown-rump length) and growth of the foot. In this study, 106 human fetuses (56 males, 50 females) without external anomalies and aged between 10-40 post-menstrual weeks (PMW) were studied. In the upper extremity, the width of shoulder and the length of the arms, forearms and hands were measured. In the lower extremity, the width of the iliac crest, knee condyles, feet, and heels and the length of the thighs, legs and feet were measured. A significant correlation was found between all parameters taken within the fetal period and PMW (p < 0.001). Statistically significant correlations found between foot-growth measurements and fetal parameters indicate that foot length may be a good predictor of age. The measurements of the upper and lower extremities during fetal period are a reliable parameter for use in the assessment of gestational age. These measurements are particularly useful when other parameters do not accurately predict gestational age in some cases such as hydrocephalus, anencephaly, short-limb dysplasia. Our opinion is that the measurements can be useful to assess gestational age in several fields such as anatomy, pathologic anatomy (fetopathology), forensic medicine, medical imaging, obstetrics and pediatrics.     

Hand development in trisomy 21

The purpose of the present study was to evaluate hand size and maturity in fetuses with trisomy 21 (Down syndrome). Twenty-five fetuses, crown-rump length (CRL) 55–222 mm, foot length (FL) 8–42 mm, were included in the study. After whole-body radiography (Hewlett Packard Faxitron), special radiographs of the hand and foot were taken. Hand length was measured as the length of the third finger from the distal tip of the distal phalanx to the proximal tip of the metacarpal bone, the digital-metacarpal length (DML). The lengths of the proximal phalangeal bone (PPL) and the metacarpal bone (MCL) of the third finger were also measured. The DML, PPL, and MCL values of each fetus were related to CRL and FL. The individual hand bones were evaluated with regard to time of appearance on radiographs, sequence in comparison with the normal sequence of appearance, and morphology. The hand length is normal during the first half of the fetal period, whereas the length of individual bones in the third finger is reduced. The normal sequence of ossification, with the middle phalanx of the fifth finger last to ossify, also occurred in Down syndrome; however, this bone appeared later in Down syndrome. In four of the fetuses it did not appear (CRLs: 125, 158, 172, and 174 mm). Am. J. Med. Genet. 79:337–342, 1998. © 1998 Wiley-Liss, Inc.     

The relation of adiposity and body size to chronological age in olive baboons

Mixed-longitudinal data on adiposity and body size were taken on 250 male and 452 female olive baboons aged between birth and 8 years. Adiposity was measured as skinfold thickness at the neck, subscapular, suprailiac, and triceps sites; body size measures included weight, crown-rump length, and triceps circumference. Males and females were treated independently and compared for gender differences. Data were tabulated to examine the relation of the somatometric variables to age and the patterns of association among the variables. Females averaged larger skinfold values at all sites for most ages. Males were significantly heavier, longer, and exhibited greater triceps girth at all ages except birth and 1 year where no significant gender difference was found for crown-rump length. In general the three measures of body size were significantly correlated at all ages as were the four measures of adiposity. Significant associations between adiposity and body size measures were not consistent among various ages.     

Theoretical kidney volume versus real kidney volume: comparative evaluation in fetuses

Summary In order to present equations and normal growth curves of the theoretical kidney volume we studied 290 kidneys taken from 145 fresh human fetuses ranging in age from 13 to 36 weeks post-conception (WPC). The kidneys were evaluated in terms of greatest longitudinal length (L) superior pole width (SW), inferior pole width (IW), thickness (T) and real volume (RV). The theoretical kidney volume was calculated (ellipsoid formula: volume = length × width × thickness × 0.5236) by using SW, IW and the arithmetic mean between SW and IW. The assessment of the theoretical volume by using IW was well correlated with the real kidney volume. We found no statistically significant difference between right and left kidneys. During the second trimester (13 to 24 WPC) there was no difference in kidney volume between male and female fetuses. In the third trimester (25 to 36 WPC) male fetuses presented kidney volumes significantly greater than female fetuses. To evaluate the theoretical kidney volume in fetuses, one may use the IW, which is a quickly and easily obtained measurement. During the second trimester one may monitor the fetal kidney using equations and growth curves without taking the fetal sex into account. During the third trimester the fetal kidney volume must be evaluated using specific curves for male and female fetuses.Supported by a grant from the National Council of Scientific and Technological Development (CNPq - Brazil - 302.369/86-4/BM-FV)     

The growth of the upper and lower extremities of Turkish fetuses during the fetal period

Prenatal analysis of the fetal structures gives us information about fetal growth and gestational age. The aim of this study was to investigate the morphologic structure of the upper and lower extremities of Turkish fetuses during the fetal period, to measure the morphometric values, and to determine the relationship between CRL (crown-rump length) and growth of the foot. In this study, 106 human fetuses (56 males, 50 females) without external anomalies and aged between 10–40 post-menstrual weeks (PMW) were studied. In the upper extremity, the width of shoulder and the length of the arms, forearms and hands were measured. In the lower extremity, the width of the iliac crest, knee condyles, feet, and heels and the length of the thighs, legs and feet were measured. A significant correlation was found between all parameters taken within the fetal period and PMW (p < 0.001). Statistically significant correlations found between foot-growth measurements and fetal parameters indicate that foot length may be a good predictor of age. The measurements of the upper and lower extremities during fetal period are a reliable parameter for use in the assessment of gestational age. These measurements are particularly useful when other parameters do not accurately predict gestational age in some cases such as hydrocephalus, anencephaly, short-limb dysplasia. Our opinion is that the measurements can be useful to assess gestational age in several fields such as anatomy, pathologic anatomy (fetopathology), forensic medicine, medical imaging, obstetrics and pediatrics.     

Fetal Hydrocephalus Caused by Cryptic Intraventricular Hemorrhage

Cryptic intracerebral hemorrhage as an etiological factor in fetal hydrocephalus has been postulated but not described at autopsy. Four fetuses with overt hydrocephalus diagnosed by in utero ultrasound examination were examined at autopsy at 19–22 weeks gestation. Although a hemorrhagic etiology was not evident on ultrasound, hemosiderin‐containing macrophages and associated reactive changes were found to obstruct the otherwise well‐formed cerebral aqueduct in all four. Coagulopathy due to thrombocytopenia was implicated in one case. Anomalies involving other parts of the body were identified in two cases, although a direct link to the hydrocephalus was not obvious. The abnormality was isolated in one case. In three cases, possible sites of hemorrhage in the ventricles were identified. This abnormality represents a significant proportion of the fetuses examined for hydrocephalus in our referral center. We discuss the importance of careful autopsy examination in the diagnosis of cryptic intracerebral hemorrhage and the implications for counseling.     

Reduction of procarbazine-induced cleft palates by prenatal folic acid supplementation in rats

We investigated the effects of prenatal folic acid supplementation on procarbazine (PCZ)-induced intra-uterine growth retardation (IUGR), cleft palates, and microgenia. Three groups of gravid rats were treated with 200 mg/kg body weight (BW) PCZ on day 13.5 of gestation (GD13.5). Two groups of them were additionally supplemented with 1 and 2.5 mg/kg folic acid, respectively, from GD13.5 through GD16.5. On GD19.5, all fetuses were delivered by caesarian sections and sexed subsequently. Numbers of live and dead fetuses as well as resorptions were counted. Data on fetal BW, crown-rump length, tail length, placental weight, and diameter were collected. Fetal heads were histologically scrutinized for the occurrence of cleft palates and microgenia. Folic acid at 2.5 mg/kg diminished PCZ-induced IUGR. In male fetuses, both folic acid doses significantly reduced the incidence of cleft palates and microgenia, while in females, only the high folic acid dose was capable of lowering the occurrence frequency of cleft palates. We conclude that folic acid supplementation at the used doses confers a substantial protection against PCZ-induced IUGR and incidence of cleft palates and microgenia. However, these effects are gender-related and dose-dependent.     

Age determination of early human embryos and fetuses

Since the number of legal abortions has increased, it has become possible to get human embryonic and fetal material for developmental and teratological studies. Unfortunately this material, due to gynaecological techniques, is usually not intact and thus the estimation of fetal age from crown-rump length is impossible. Usually, however, one or both feet are available; thus, in this paper, foot lengths of 201 embryos and fetuses are correlated with menstrual ages. The mean foot lengths are from 2.9 to 18.5 mm and the age range from 7 to 16 weeks, respectively. Comparison with Streeter's measurements (1920) is also made.     

Haematological and obstetric aspects of antenatal diagnosis of beta-thalassaemia: experience with 200 cases.

The results of 200 antenatal diagnoses in pregnancies at risk for homozygous beta-thalassaemia, carried out on fetal blood samples obtained by placental aspiration in the second trimester, are described. Globin chain synthesis in the fetuses was measured by means of 3H-leucine incorporation and separation of the chains on carboxy-methyl-cellulose columns. Fetal red cell enrichment was performed by NH4Cl-NH4HCO3 differential lysis of maternal cells or anti-i differential agglutination. Sufficient fetal blood for analysis was obtained in 97.5% of the cases. The overall fetal loss rate was 6.5%, but it declined from 10% in the first consecutive 100 cases to 3% in the last 100 cases. Fetal loss was the result of early or late intrauterine death or spontaneous abortion. Forty-two homozygous fetuses had no beta-chain synthesis and one had a very low beta/gamma ratio (0.005). Of the pregnancies, 37 were terminated at parental request and four aborted spontaneously. Absence of beta-chain radioactivity was confirmed in 12 abortuses with suitable cord blood samples for analysis. Two pregnancies with homozygous fetuses were not terminated, as one member of each couple was a devout Catholic. As expected, both infants developed Cooley's anaemia. Follow-up of the 146 infants, diagnosed in utero as non-homozygotes, showed cerebral palsy in one and a small cutaneous needle injury in three. None of these developed homozygous beta-thalassaemia. Even beta-thalassaemia trait with a beta/gamma ratio of 0.046 +/- 0.012 can be distinguished from normal, showing a beta/gamma ratio of 0.086 +/- 0.019 with a high degree of certainty.     

Pregnancy outcome and infant follow-up of fetuses with abnormally increased first trimester nuchal translucency

The numbers of fetuses with an abnormal increased first trimester nuchal translucency (NT) but a confirmed normal anatomy and karyotyping is relatively small and therefore a challenge for prenatal counselling. The aim of the current study was to assess the long-term pregnancy outcome and infancy prognosis of 78 fetuses with NT > 95th centile of the normal range for crown-rump length (CRL). The most common abnormalities in this group were aneuploidy, which affected 32 of the fetuses followed by four and three cases which were miscarried or had cardiac defects respectively. The remaining euploid fetuses with normal detailed scans were followed throughout their infancy (mean 24 months; range 12-36 months). Post-natally, except for a correctable case of ventricular septal defect and a case of posterior urethral valve, no other abnormalities were detected. After excluding all aneuploid cases and using the maternal age as a second variable, an uncomplicated pregnancy outcome could be anticipated in 17 cases (100%) when the maternal age was <30 years and NT between 95th centile and 5 mm. However, the chance of a normal outcome dropped to 50% in four cases with maternal age > or =30 years and NT > or =5 mm (Fisher's exact test; P: = 0.02). These findings suggest that the long-term prognosis of the euploid fetuses with large NT (<5 mm) is reassuring in younger women.