Metabolomic Profile of Umbilical Cord Blood Plasma from Early and Late Intrauterine Growth Restricted (IUGR) Neonates with and without Signs of Brain Vasodilation

Objectives

To characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR).

Methods

23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA) controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight <10^th centile, abnormal umbilical artery (UA) Doppler and delivery <35 weeks. Late IUGR was defined as a birth weight <10^th centile with normal UA Doppler and delivery >35 weeks. This group was subdivided in 18 vasodilated (VD) and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10^th centile. ¹H nuclear magnetic resonance (NMR) metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data.

Results

The NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR.

Conclusions

IUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.     

Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb

Intrauterine growth restriction (IUGR) is associated with accelerated growth after birth. Together, IUGR and accelerated growth after birth predict reduced lean tissue mass and increased obesity in later life. Although placental insufficiency is a major cause of IUGR, whether it alters growth and adiposity in early postnatal life is not known. We hypothesized that placental restriction (PR) in the sheep would reduce size at birth and increase postnatal growth rate, fat mass, and feeding activity in the young lamb. PR reduced survival rate and size at birth, with soft tissues reduced to a greater extent than skeletal tissues and relative sparing of head width (P < 0.05 for all). PR did not alter absolute growth rates (i.e., the slope of the line of best fit for age vs. parameter size from birth to 45 days of age) but increased neonatal fractional growth rates (absolute growth rate relative to size at birth) for body weight (+24%), tibia (+15%) and metatarsal (+18%) lengths, hindlimb (+23%) and abdominal (+19%) circumferences, and fractional growth rates for current weight (P < 0.05) weekly throughout the first 45 days of life. PR and small size at birth reduced individual skeletal muscle weights and increased visceral adiposity in absolute and relative terms. PR also altered feeding activity, which increased with decreasing size at birth and was predictive of increased postnatal growth and adiposity. In conclusion, PR reduced size at birth and induced catch-up growth postnatally, normalizing weight and length but increasing adiposity in early postnatal life. Increased feeding activity may contribute to these alterations in growth and body composition following prenatal restraint and, if they persist, may lead to adverse metabolic and cardiovascular outcomes in later life.     

Reference Values for Body Composition and Anthropometric Measurements in Athletes

Background

Despite the importance of body composition in athletes, reference sex- and sport-specific body composition data are lacking. We aim to develop reference values for body composition and anthropometric measurements in athletes.

Methods

Body weight and height were measured in 898 athletes (264 female, 634 male), anthropometric variables were assessed in 798 athletes (240 female and 558 male), and in 481 athletes (142 female and 339 male) with dual-energy X-ray absorptiometry (DXA). A total of 21 different sports were represented. Reference percentiles (5^th, 25^th, 50^th, 75^th, and 95^th) were calculated for each measured value, stratified by sex and sport. Because sample sizes within a sport were often very low for some outcomes, the percentiles were estimated using a parametric, empirical Bayesian framework that allowed sharing information across sports.

Results

We derived sex- and sport-specific reference percentiles for the following DXA outcomes: total (whole body scan) and regional (subtotal, trunk, and appendicular) bone mineral content, bone mineral density, absolute and percentage fat mass, fat-free mass, and lean soft tissue. Additionally, we derived reference percentiles for height-normalized indexes by dividing fat mass, fat-free mass, and appendicular lean soft tissue by height squared. We also derived sex- and sport-specific reference percentiles for the following anthropometry outcomes: weight, height, body mass index, sum of skinfold thicknesses (7 skinfolds, appendicular skinfolds, trunk skinfolds, arm skinfolds, and leg skinfolds), circumferences (hip, arm, midthigh, calf, and abdominal circumferences), and muscle circumferences (arm, thigh, and calf muscle circumferences).

Conclusions

These reference percentiles will be a helpful tool for sports professionals, in both clinical and field settings, for body composition assessment in athletes.     

Models of Intrauterine growth restriction and fetal programming in rabbits

Intrauterine growth restriction (IUGR) affects approximately 10% of human pregnancies globally and has immediate and life‐long consequences for offspring health. However, the mechanisms underlying the pathogenesis of IUGR and its association with later health and disease outcomes are poorly understood. To address these knowledge gaps, the use of experimental animals is critically important. Since the 50's different environmental, pharmacological, and surgical manipulations have been performed in the rabbit to improve our knowledge of the control of fetal growth, fetal responses to IUGR, and mechanisms by which offspring may be programmed by an adverse gestational environment. The purpose of this review is therefore to summarize the utility of the rabbit as a model for IUGR research. It first summarizes the knowledge of prenatal and postnatal development in the rabbit and how these events relate to developmental milestones in humans. It then describes the methods used to induce IUGR in rabbits and the knowledge gained about the mechanisms determining prenatal and postnatal outcomes of the offspring. Finally, it discusses the application of state of the art approaches in the rabbit, including high‐resolution ultrasound, magnetic resonance imaging, and gene targeting, to gain a deeper integrative understanding of the physiological and molecular events governing the development of IUGR. Overall, we hope to engage and inspire investigators to employ the rabbit as a model organism when studying pregnancy physiology so that we may advance our understanding of mechanisms underlying IUGR and its consequences in humans and other mammalian species.     

Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development

Low birth weight resulting from intrauterine growth retardation (IUGR) is a risk factor for further development of metabolic diseases. The pig appears to reproduce nearly all of the phenotypic pathological consequences of human IUGR and is likely to be more relevant than rodents in studies of neonatal development. In the present work, we characterized the model of low-birth-weight piglets with particular attention to the hypothalamic leptin-sensitive system, and we tested whether postnatal leptin supplementation can reverse the precocious signs of adverse metabolic programming. Our results demonstrated that 1) IUGR piglets present altered postnatal growth and increased adiposity; 2) IUGR piglets exhibit abnormal hypothalamic distribution of leptin receptors that may be linked to further disturbance in food-intake behavior; and 3) postnatal leptin administration can partially reverse the IUGR phenotype by correcting growth rate, body composition, and development of several organs involved in metabolic regulation. We conclude that IUGR may be characterized by altered leptin receptor distribution within the hypothalamic structures involved in metabolic regulation and that leptin supplementation can partially reverse the IUGR phenotype. These results open interesting therapeutic perspectives in physiopathology for the correction of defects observed in IUGR.     

Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development

Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A₂-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent “first hit”, rendering IUGR intestine susceptible to further injury, infection, or inflammation.     

Synergistic effects of prenatal hypoxia and postnatal high-fat diet in the development of cardiovascular pathology in young rats

We have previously shown that adult offspring exposed to a prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) are more susceptible to cardiovascular pathologies. Our objectives were to evaluate the interaction between hypoxia-induced IUGR and postnatal diet in the early development of cardiovascular pathologies. Furthermore, we sought to determine whether the postnatal administration of resveratrol could prevent the development of cardiovascular disorders associated with hypoxia-induced IUGR. On day 15 of pregnancy, Sprague-Dawley rats were randomly assigned to hypoxia (11.5% oxygen), to induce IUGR, or normal oxygen (control) groups. For study A, male offspring (3 wk of age) were randomly assigned a low-fat (LF, <10% fat) or a high-fat (HF, 45% fat) diet. For study B, offspring were randomized to either HF or HF+resveratrol diets. After 9 wk, cardiac and vascular functions were evaluated. Prenatal hypoxia and HF diet were associated with an increased myocardial susceptibility to ischemia. Blood pressure, in vivo cardiac function, and ex vivo vascular function were not different among experimental groups; however, hypoxia-induced IUGR offspring had lower resting heart rates. Our results suggest that prenatal insults can enhance the susceptibility to a second hit such as myocardial ischemia, and that this phenomenon is exacerbated, in the early stages of life by nutritional stressors such as a HF diet. Supplementing HF diets with resveratrol improved cardiac tolerance to ischemia in offspring born IUGR but not in controls. Thus we conclude that the additive effect of prenatal (hypoxia-induced IUGR) and postnatal (HF diet) factors can lead to the earlier development of cardiovascular pathology in rats, and postnatal resveratrol supplementation prevented the deleterious cardiovascular effects of HF diet in offspring exposed to prenatal hypoxia.     

Focus: The Science of Stress: Can Maternal Prenatal Self-Reported and Physiological Distress Predict Postnatal Caregiving Practices?

Maternal prenatal distress is associated with child outcomes, including health, neurocognitive, and socio-emotional development. Knowledge on underlying mechanisms is limited, yet relevant for prevention and intervention. This study investigated whether maternal prenatal distress predicts specific caregiving practices that are known for their effects on child outcomes. Caregiving practices studied were maternal caregiving quality and the initiation and course of breastfeeding and room-sharing. We hypothesized that more maternal prenatal distress would be associated with altered caregiving practices. Participants were 174 healthy mother-child dyads. During the 37^th week of pregnancy maternal self-reported distress was assessed using questionnaires, and physiological stress by collecting saliva cortisol. Maternal caregiving quality was observed in postnatal week 5 during infant bathing. Weekly diaries on breastfeeding and daily diaries on room-sharing were completed during the first 6 postnatal months. In a regression analysis, no associations between maternal prenatal distress and caregiving quality were found. Multilevel analyses indicated that maternal prenatal evening cortisol was positively related to the initiation of breastfeeding and room-sharing. Replications are warranted, but these results suggest that breastfeeding and room-sharing initiation may be part of a mechanism underlying links between maternal prenatal physiological stress and child outcomes. As other prenatal cortisol markers and self-reported distress were not found to be related to the caregiving practices, it is likely that alternative mechanisms (co-)exist in explaining links between maternal prenatal distress and child outcomes. Future replication research including child outcomes and (other) potential mechanisms will inform prevention and intervention programs fostering healthy pregnancies and child development.     

Prognostic Value of Umbilical and Cerebral Doppler in Fetal Growth Restriction: Comparison of Dichorionic Twins and Singletons

Objective

To compare the prognostic value of fetal Doppler in dichorionic twins and singletons by measuring the interval between diagnosis of an abnormal Doppler flow and birth in fetuses who are small for gestational age (SGA).

Design

Comparative retrospective study using a prospectively collected database.

Setting

A level 3 maternity unit in France.

Population

Fetuses from singleton and dichorionic pregnancies who are SGA (vascular or unexplained), defined by an abdominal circumference (AC) measurement below the 10^th percentile and confirmed by a birth weight below the 10^th percentile.

Methods

Fisher''s exact and Chi-2 tests were used to compare frequencies, and the Mann-Whitney-Wilcoxon test was used to compare medians in non-Gaussian distributions.

Main outcome measures

Both neonatal outcomes and intervals between the first Doppler abnormality and birth were compared in the groups of dichorionic twins and singletons.

Results

Obstetric and neonatal outcome were similar in the 104 SGA dichorionic twins and 170 SGA singletons. Abnormalities of umbilical artery Doppler, regardless of type, appeared at the same frequency in both groups (52.9%) but were identified earlier in twins (25 versus 28 weeks, p = 0.02). Among fetuses with abnormal Doppler flow, the interval between the finding and birth was significantly longer in the twins than the singletons (44 vs 15 days, p<0.01).

Conclusions

The prognostic value of an abnormal Doppler finding for the course of a pregnancy may be different in dichorionic twins and singletons. The management of women carrying SGA twins and the information provided to them should take these results into account.     

Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition

The degree of nutrient enhancement during the newborn period may modulate programming of appetite-regulating hormones, body composition, and propensity to adult obesity in intrauterine growth-restricted (IUGR) newborns. Pregnant rats received, from day 10 to term gestation and throughout lactation, ad libitum food (AdLib) or 50% food restriction (FR) to produce IUGR newborns. AdLib vs. FR offspring were studied at day 1, and, to create two distinct groups of newborn catch-up growth (immediate, delayed) among the IUGR newborns, cross-fostering techniques were employed. The four groups of pups at 3 wk were IUGR immediate catch-up growth (FR/AdLib), IUGR delayed catch-up growth (FR/FR), control (AdLib/AdLib), and lactation FR control (AdLib/FR). From 3 wk to 9 mo, all offspring had AdLib rat chow. Maternal FR during pregnancy resulted in IUGR pups (6.0 +/- 0.3 vs. 7.1 +/- 0.3 g, P < 0.01) with decreased leptin (0.66 +/- 0.03 vs. 1.63 +/- 0.12 ng/ml, P < 0.001) and increased ghrelin (0.43 +/- 0.03 vs. 0.26 +/- 0.02 ng/ml, P < 0.001). Maternal FR during lactation (FR/FR) further impaired IUGR offspring growth at 3 wk. However, by 9 mo, these pups attained normal body weight, percent body fat, and plasma leptin levels. Conversely, IUGR offspring nursed by AdLib dams (FR/AdLib) exhibited rapid catch-up growth at 3 wk and continued accelerated growth, resulting in increased weight, percent body fat, and plasma leptin levels. Thus the degree of newborn nutrient enhancement and timing of IUGR newborn catch-up growth may determine the programming of orexigenic hormones and offspring obesity.     

Prenatal Exposure to Lipopolysaccharide Results in Local RAS Activation in the Adipose Tissue of Rat Offspring

Background

Adult metabolic syndrome may originate in part during fetal or early life. This study was designed to investigate the effects of prenatal exposure to lipopolysaccharide (LPS) on adipose development and local renin-angiotensin system (RAS) activation in rat offspring.

Methods

Pregnant rats were randomly divided into three groups (n = 8 in each), including an NS group (pregnant rats were only treated with 0.5 ml normal saline from the 8^th to the 14^th day of gestation); an LPS group (pregnant rats were injected intraperitoneally with 0.79 mg/kg LPS on the 8^th, 10^th and 12^th days of pregnancy); and an LPS+pyrrolidine dithiocarbamate (PDTC) group (identical to the LPS group except that 100 mg/kg PDTC was administered from the 8^th to the 14^th day of gestation).

Results

Prenatal exposure to LPS resulted in increased blood pressure, adipose coefficient and body weight in rat offspring. Specifically, during the infancy of the offspring rats, the LPS stimulus promoted the differentiation of adipose cells, diminishing their diameters and proportions while simultaneously increasing cell number. In contrast, once the rats were grown, adipose cell differentiation was inhibited, and the diameters and proportions of the cells were increased. Moreover, each component of the RAS was changed and was shown to be activated. PDTC, an inhibitor of NF-κB, could reverse the influence of the stimulus during pregnancy.

Conclusion

Prenatal exposure to LPS in rats results in increased blood pressure, adipose coefficient, body weight and activation of adipose RAS in offspring.     

Glucose metabolic adaptations in the intrauterine growth-restricted adult female rat offspring

We studied glucose metabolic adaptations in the intrauterine growth-restricted (IUGR) rat offspring to decipher glucose homeostasis in metabolic programming. Glucose futile cycling (GFC), which is altered when there is imbalance between glucose production and utilization, was studied during a glucose tolerance test (GTT) in 2-day-old (n = 8), 2-mo-old (n = 22), and 15-mo-old (n = 22) female rat offspring. The IUGR rats exposed to either prenatal (CM/SP, n = 5 per age), postnatal (SM/CP, n = 6), or pre- and postnatal (SM/SP, n = 6) nutrient restriction were compared with age-matched controls (CM/CP, n = 5). At 2 days, IUGR pups (SP) were smaller and glucose intolerant and had increased hepatic glucose production and increased glucose disposal (P < 0.01) compared with controls (CP). At 2 mo, the GTT, glucose clearance, and GFC did not change. However, a decline in hepatic glucose-6-phosphatase (P < 0.05) and fructose-1,6-biphosphatase (P < 0.05) enzyme activities in the IUGR offspring was detected. At 15 mo, prenatal nutrient restriction (CM/SP) resulted in greater weight gain (P < 0.01) and hyperinsulinemia (P < 0.001) compared with postnatal nutrient restriction (SM/CP). A decline in GFC in the face of a normal GTT occurred in both the prenatal (CM/SP, P < 0.01) and postnatal calorie (SM/CP, P < 0.03) and growth-restricted offspring. The IUGR offspring with pre- and postnatal nutrient restriction (SM/SP) were smaller, hypoinsulinemic (P < 0.03), and hypoleptinemic (P < 0.03), with no change in GTT, hepatic glucose production, GFC, or glucose clearance. We conclude that there is pre- and postnatal programming that affects the postnatal compensatory adaptation of GFC and disposal initiated by changes in circulating insulin concentrations, thereby determining hepatic insulin sensitivity in a phenotype-specific manner.     

Neurobehavioral changes in mice offspring induced by prenatal exposure to acute toxicity of sodium selenite

Selenium is an essential element with a narrow margin between beneficial and toxic effects. This study was aimed to determine the neurobehavioral changes resulted from the prenatal exposure of mice to high doses of sodium selenite during fetal and early postnatal development. Atomic absorption for monitoring the placental transfer of selenium to offspring was employed. The developmental observations as well as the behavioral tests, such as sensory motor reflexes, and learning and memory test in automatic reflex conditioner (shuttle box) (active avoidance responses) were applied. Adult mice was assigned into three groups: the first group was remained as a control group given phosphate buffered saline; the second and the third groups were orally administrated sodium selenite at doses of 1 mg/kg and 4 mg/kg of the diet, respectively started from the 7^th day to the end of the gestation period. Appearance of body hair and opening of eyes of the pups from treated mothers were delayed in a dose-dependent manner. The body weight gain came significantly lower than those of the control especially at the higher dose. Selenite also inhibited the sensory motor reflexes in all elements of acts and postures in a dose dependent manner. The active avoidance training-test indicated that selenite exposure was associated with learning impairment. Acetylcholine recorded a significant decrease in almost all the period of this study. By using atomic absorption, we found a significant high concentration of selenium in the brain, liver and kidney until the 40^th postnatal day, indicating active transfer of selenium from mothers to embryos.     

Evaluation of the influence of diet supplementation with conjugated linoleic acid isomers on elemental composition in the cardio-oncological nutritional programming rat’ model

BackgroundThe ‘developmental origin of health and disease’ (DOHaD) hypothesis assumes that due to the action of some stimuli during fetal life the long-term physiological changes occurs and may affects the risk of various diseases. The main aim of this study was to assess impact of supplementation of maternal’ and early postnatal diet with conjugated linoleic acids (CLA) isomers on selected elements content in hearts of their female offspring with chemically induced breast cancer.MethodsElemental composition was determined by quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS).ResultsThe effect of maternal’ diet on the elements content was more pronounced than the progeny diet modifications. Significant correlations among determined elements, especially macroelements, and lipidomic parameters, in the experimental factors dependent manner were observed. It can be concluded that supplementation of maternal and progeny diets with CLA isomers may significantly influence the contents of both macro- and microelements in cardiac tissue of newborns.ConclusionOur results also indicate, that dynamic and intricate balance among various elements in body may be affected by the lipid dietary supplements also in the pathological state. Utility of cardio-oncological approach in developmental programming study was confirmed.     

The Development of Upper Limb Movements: From Fetal to Post-Natal Life

Background

The aim of this longitudinal study was to investigate how the kinematic organization of upper limb movements changes from fetal to post-natal life. By means of off-line kinematical techniques we compared the kinematics of hand-to-mouth and hand-to-eye movements, in the same individuals, during prenatal life and early postnatal life, as well as the kinematics of hand-to-mouth and reaching-toward-object movements in the later age periods.

Methodology/Principal Findings

Movements recorded at the 14^th, 18^th and 22^nd week of gestation were compared with similar movements recorded in an ecological context at 1, 2, 3, 4, 8, and 12 months after birth. The results indicate a similar kinematic organization depending on movement type (i.e., eye, mouth) for the infants at one month and for the fetuses at 22 weeks of gestation. At two and three months such differential motor planning depending on target is lost and no statistical differences emerge. Hand to eye movements were no longer observed after the fourth month of life, therefore we compared kinematics for hand to mouth with hand to object movements. Results of these analyses revealed differences in the performance of hand to mouth and reaching to object movements in the length of the deceleration phase of the movement, depending on target.

Conclusion/Significance

Data are discussed in terms of how the passage from intrauterine to extra-uterine environments modifies motor planning. These results provide novel evidence of how different types of upper extremity movements, those directed towards one’s own face and those directed to external objects, develop.     

Medium chain fatty acids in intrauterine growth restricted and small for gestational age pregnancies

Introduction

Low birth weight is associated with an increased risk of heart disease, high blood pressure and diabetes in adult life. Fetal growth is determined by nutrient availability, which is related to placenta nutrient transport. Medium chain fatty acids (MCFAs) are a particular class of nutrients, known to be a readily available energy source. Until now no data are reported on these MCFAs in low birth weight fetus.

Aim

This is a prospective study conducted in a tertiary center of prenatal diagnosis to investigate the maternal and fetal MCFAs levels in appropriate for gestational age (AGA), intrauterine growth restricted (IUGR), and small for gestational age (SGA) pregnancies.

Method

The plasmatic levels of MCFAs in AGA, IUGR and SGA mother–infant pairs were quantified by gas chromatography–mass spectrometry. The analytical method had a linearity range of 0.1–50 mg/L and a limit of quantification of 0.03 mg/L. Reduced fetal growth was defined as an estimated fetal weight below the 3rd–10th percentile for gestational age, with (IUGR) or without (SGA) fetal Doppler abnormalities.

Result

Maternal and fetal MCFAs plasma levels were significantly different among SGA, IUGR and AGA groups. Additionally, the observed MCFAs fetal to maternal ratio is >1 for IUGR group, whilst for SGA and AGA the fetal to maternal ratio is less than one.

Conclusion

Changes in MCFAs levels in fetal and maternal plasma are not related to placental functionality or nutrients availability, suggesting the presence of a de novo biosynthesis.

     

Age-related changes in the rates of polypeptide chain elongation

The time of an average polypeptide chain synthesis, ts, in the liver and brain cortex of rats of various age--from the 17th day of prenatal life up to the 24th month of the postnatal period--was estimated. At the end of the prenatal period the value of t is much higher than in postnatal life. In newborns, the t value is minimal, showing a gradual increase during the postnatal development. Determination of an average molecular mass of newly synthesized polypeptides demonstrated that the increase of t in postnatal life is due to the decrease of the rate of polypeptide chain elongation.