The role of imprinted genes in fetal growth

Genomic imprinting is the phenomenon by which one of the two alleles of a subset of genes is preferentially expressed according to its parental origin. This pattern of inheritance is different from the more frequent mode of Mendelian inheritance, which is not influenced by the parental origin of the allele. The idea that imprinted genes can affect fetal growth is becoming increasingly intriguing as it has been shown that most imprinted genes are expressed in the placenta and some play a role in regulating the interactions between its fetal and maternal interfaces. This article considers genomic imprinting by reviewing recent findings of alterations in fetal growth related to different types of genetic changes affecting the expression of imprinted genes. Among the genetic anomalies, the uniparental disomy (UPD) defines the inheritance of both homologous chromosomes from only one parent. UPDs of a number of chromosomes have been described in association with effects on the phenotype. We reviewed cases of UPD reported till now with particular reference to those associated to growth alterations.     

Lack of influence of maternal and fetal transferrin phenotypes and concentrations on normal fetal growth

Influence of maternal and fetal transferrin types and concentrations on the fetal growth has been investigated in 1,174 normal full-term singleton newborns, including 352 mother-newborn pairs. No significant effect of these parameters was observed on the weight and length of the newborns. Newborn plasma transferrin concentration was not correlated with maternal plasma transferrin concentration.     

Sex steroids do not influence somatic growth in childhood

The influence of sex steroids on somatic growth during childhood was evaluated by reviewing linear growth characteristics of 18 agonadal patients with normal sex chromosomes. None of the heights throughout childhood and before the onset of sex steroid therapy were below 2 SDs of the mean. Based on the normal z scores of these patients, we concluded that somatic growth throughout the childhood and prepubertal years is not sex-steroid dependent.     

Obesity genes: implication in childhood obesity

Overweight and obesity prevalence has dramatically increased during the last decade and reached epidemic dimensions. By 2030 it is expected that there will be 2.16 billion overweight individuals with 1.12 billion adults predicted to be clinically obese. Obesity is caused by both genetic and non-genetic factors. BMI as a common measure of obesity is a highly heritable trait with heritability estimates of ～0.7 for both adults and children. Mutations in a few genes such as LEPR and MC4R identified by molecular genetic analysis in children are known to be involved in rare monogenic severe obesity. Their identification opened important insights in fundamental pathways, in particular the leptin-melanocortin pathway, involved in control of appetite and energy metabolism. However, the polygenic basis of common obesity with many common variants conferring each modest risk to the phenotype is still one of the major challenges in genetics of obesity. Driven by the availability of genome wide association (GWAS) technology enabling analysis of millions of markers in thousands of individuals, multiple polymorphisms/genes have been identified in the last 5 years. With common genetic variants in genes such as FTO (fat mass and obesity-associated gene) a great number of additional susceptibility variants have been identified altogether still accounting for a small percentage of the overall risk for obesity. This review outlines the progress of research in genetics of obesity during recent years in adults and children.     

Altitude and childhood growth

To assess the possible influence of altitude on childhood growth in the United States, we used data collected by the Centers for Disease Control Pediatric Nutrition. Surveillance System from eight mountain states to determine the height and weight status of children aged 5 years or younger enrolled in various public health programs between 1982 and 1984. The mean birth weight, height-for-age, weight-for-age, and weight-for-height indicators were found to decline significantly with increasing altitude, starting at an elevation greater than 1500 m (p less than 0.001, ANOVA). The reduction in growth was observed for all age groups and all birth weight groups studied. Part of the observed reduction in growth could be attributed to the lower birth weight of children born at higher altitude. However, the reduced growth status persisted after controlling for birth weight, suggesting the presence of an extrauterine growth retardation effect related to altitude.     

The influence of maternal cortisol and emotional state during pregnancy on fetal intrauterine growth

Background:This exploratory study investigates the influence of maternal cortisol and emotional state during pregnancy on fetal intrauterine growth (IUG). We expected higher basal cortisol levels, or more depressive and anxious complaints during pregnancy, to be associated with slower IUG and lower birth weight.Methods:A total of 91 pregnant women were recruited from the antenatal clinic and were seen once each trimester. In addition to psychological assessments, a diurnal cortisol profile was derived from saliva samples. IUG was evaluated using ultrasound.Results:In mid-pregnancy (trimester (T)2), basal cortisol levels significantly predicted the variance of weight (proportion of variance in growth variable explained (PVE) = 11.6%) and body mass index (BMI) at birth (PVE = 6.8%). In late pregnancy (T3) emotional state, particularly depressive symptoms (BMI at birth: PVE = 6.9%; ponderal index (PI) at birth: PVE = 8.2%; head circumference at T3: PVE = 10.3%; head circumference at birth PVE = 9.1%) and attachment (BMI at birth: PVE = 6.9%; PI at birth: PVE = 7.2%) had an influence on growth. Analysis of growth between T2 and T3 showed that attachment and cortisol in T3 had an influence on the variation in increase in estimated fetal weight (PVE = 12.5-8.6%).Conclusion:These data indicate basal cortisol levels were more important in T2 whereas emotional state was more important in T3.     

Modeling of the human fetal skull base growth: interest in new volumetrics morphometric tools

Background

Research on the skull base is important to improve our understanding of the growth and development of the modern human skull. To study the growth of the human fetal skull base, we assessed a new geometric morphometric tool, which does not require the use of bone landmarks.

Material and methods

Seven dry fetal skulls of an estimated gestational age ranging from 15 to 27 weeks were studied. Each skull was scanned using a standard CT scan and the image sets were post-processed to extract volumetric data by segmenting the skull base into predefined regions of interest. Our method of analysis was based on the inertial properties of reconstructed volumes.

Results

The volumetric study of the skulls highlighted an asynchronous speed of growth between the pre and post-chordal parts of the skull base whose preferential growth are in the vertical and horizontal planes. We also found different speeds of growth in the pre-chordal part depending on the type of ossification (endochondral or membranous). The overall shape of the skull base bones were preserved during the period studied except for the petrous pyramids. The expansion of bone parts was isometric with reference to a central point that was located at the intrasphenoidal synchondrosis. Finally, the analysis of the basicranial angles corroborated data from the literature in the sagittal plane and allowed their study also in the frontal and horizontal planes.

Conclusions

This three-dimensional volumetric approach is a necessary complement to studies that are performed in the sagittal plane and are based on the identification of landmarks. The geometric morphometric method used by authors permitted to obtain original informations on the growth kinetics and bone tridimensional movements of the human fetal skull base.     

Birth weight and childhood growth

Most previous studies of the relationship between birth weight and childhood growth have concentrated on the growth of low birth weight infants. To examine this relationship throughout the full range of birth weights, growth data for children less than 5 years of age from the Tennessee Special Supplemental Food Program for Women, Infants, and Children linked to birth certificate records for 1975 to 1985 were used. Growth status was compared for 500-g birth weight categories from 1,000 g to 4,999 g using mean Z scores and the percentage of children more than 2 SD above or less than 2 SD below the median for height for age, weight for age, and weight for height. Infants with lower birth weights were likely to remain shorter and lighter throughout childhood, especially those who were intrauterine growth retarded rather than premature. Conversely, those infants with higher birth weights were likely to remain taller and heavier and to have a higher risk of obesity. Birth weight is a strong predictor of weight and height in early childhood, not only for low birth weight children but also for those of normal and high birth weight.     

Prematurity and fetal growth restriction

Assessment of the growth status of the fetus and neonate is an essential component of perinatal care. It requires a distinction to be made between physiological and pathological factors, and the prediction of the optimal growth that a baby can achieve in a normal, uncomplicated pregnancy. Such an individually customised standard can now be easily calculated by computer: it needs to be accurately dated, individually adjusted for physiological characteristics, exclude pathological factors such as smoking, and be based on a fetal weight trajectory derived from normal term pregnancies. Application of a customised standard to calculate the growth status of preterm babies gives us freshly insights into the causes of prematurity. Fetal growth restriction is seen as a strongly associated factor, which is often present before the onset of spontaneous preterm labour. This raises the question whether, in many instances, the initiation of parturition should be seen as a fetal adaptive response aimed at escaping an unfavourable intrauterine environment. These concepts have implications for the understanding of the pathophysiology of preterm labour, as well as its clinical management.     

Insulin deficiency: Effects on fetal growth and development

Insulin deficiency in either the mother or foetus has significant effects on fetal growth and development. In the human, maternal insulin deficiency, or diabetes mellitus, leads to macrosomia and increased adiposity of the foetus, while specific fetal hypo-insulinaemia is associated with intra-uterine growth retardation. When maternal diabetes is induced in experimental animals, no consistent increases in fetal bodyweight are observed although the body fat content of the foetus is increased in the majority of species studied. The magnitude of the fetal weight gain during maternal diabetes appears to be determined by the body fat content of the foetus, the severity and duration of the diabetes and by the temporal pattern of maternal hyperglycaemia observed during pregnancy. The latter factors, in particular, influence the level of insulin in the foetus which, in turn, regulates the rate of intra-uterine growth. By contrast, fetal insulin deficiency has a more uniform effect on fetal growth and leads to impaired growth in both experimental and naturally occurring hypo-insulinaemic conditions. Fetal insulin deficiency reduces fetal growth by decreasing nutrient uptake and utilization of the fetal tissues and by altering the circulating concentrations of the insulin-like growth factors. Consequently, deficiencies in either fetal or maternal insulin secretion during pregnancy can alter fetal growth and have important consequences for perinatal survival and postnatal morbidity.     

Three-dimensional and four-dimensional fetal echocardiography: a new frontier

PURPOSE OF REVIEW: One of the difficulties of conventional two-dimensional cardiac imaging is the inability to examine fetal cardiac anatomy from multiple angle planes. Three-dimensional and four-dimensional ultrasound allows the fetal examiner to more accurately accomplish this task. Currently, multiple disciplines may be involved in the examination of the fetal heart (pediatric cardiologists, obstetricians, maternal-fetal medicine specialists, and radiologists). The three-dimensional and four-dimensional imaging equipment used by these specialty physicians varies greatly. The purpose of this communication is to review techniques using three-dimensional and four-dimensional imaging that the pediatric cardiologist may not be exposed to in the clinical environment, however, in consulting with colleagues needs to have an understanding of these imaging modalities. RECENT FINDINGS: The reconstruction of cardiac structures using this technology allows the examiner to view cardiac anatomy in a manner that was limited by previous two-dimensional imaging. Volume datasets are obtained in the three-dimensional static mode (no cardiac motion) or using four-dimensional - the three-dimensional heart is observed contracting during one or multiple cardiac cycles. Therefore, the fourth dimension is time. Using either three-dimensional or four-dimensional technology datasets are acquired, followed by image reconstruction. The image reconstruction enables the examiner to evaluate a two-dimensional image using multiple views, evaluate intracardiac anatomy at different depth planes, and recreate casts of blood flow of the chambers and great vessels. SUMMARY: This new technology has enhanced the ability of the examiner to identify normal and complex fetal heart anatomy during the early second to the late third trimesters of pregnancy.