Effects Of Intrauterine Growth Retardation Research Articles

Retard de croissance intra-utérin, ses conséquences à la naissance, dans l’enfance et à long terme

The authors report the consequence of intra-uterine growth retardation on infancy and adult disease. During infancy in 7 to 10% of cases a growth retardation less than -2 DS, is observed and subsequently needs growth hormone treatment. In adult X syndrome (hypertension, diabetes of 2 types insulino resistant and cardiovascular disease) is observed 18 times more in subjects where the birth weight was low than 2.4 kg. Finally the authors give some recommendations to follow-up of the infants born with a growth restriction.

Intrauterine growth retardation and puberty in girls.

Some, albeit not all studies on the relationship between intrauterine growth retardation (IUGR) and female pubertal development have found an earlier and rapidly progressing puberty as well as concomitant disorders of related functional systems such as polycystic ovary syndrome and short stature. These pubertal changes are part of a growing list of IUGR-related diseases, which includes non-insulin dependent diabetes mellitus and coronary heart disease. A pulsatile release of gonadotropin releasing hormone is thought to be a conditio-sinne-qua-non for the initiation of puberty. In the absence of prospective studies on gonadotropin releasing hormone pulse patterns in IUGR-children other markers of pubertal development such as age at menarche have been deployed. From these studies it is not clear, however, whether the findings of an earlier onset of puberty in IUGR-girls merely reflect a more rapid progression of puberty. Both the role for IUGR and the mechanisms behind the onset of puberty are still elusive. Assuming a connection between IUGR and pubertal development, parallels can be drawn between hypotheses on the longterm consequences of IUGR and hypotheses on the initiation of puberty. For example, the somatometer concept proposes a role for fat mass in the initiation of puberty, which is compatible with the hypothesis on non-skeletal catch-up growth after IUGR. The debate on the origins of puberty and the role of IUGR mainly focuses on nature and nurture. Judgmentally, studies in mono- and dizygotic twins discordant for birth weight may be of particular help.

Intrauterine Growth Retardation and Puberty in Girls

AbstractSome, albeit not all studies on the relationship between intrauterine growth retardation (IUGR) and female pubertal development have found an earlier and rapidly progressing puberty as well as concomitant disorders of related functional systems such as polycystic ovary syndrome and short stature. These pubertal changes are part of a growing list of IUGR-related diseases, which includes non-insulin dependent diabetes mellitus and coronary heart disease. A pulsatile release of gonadotropin releasing hormone is thought to be a conditio-sinne-qua-non for the initiation of puberty. In the absence of prospective studies on gonadotropin releasing hormone pulse patterns in IUGR-children other markers of pubertal development such as age at menarche have been deployed. From these studies it is not clear, however, whether the findings of an earlier onset of puberty in IUGR-girls merely reflect a more rapid progression of puberty. Both the role for IUGR and the mechanisms behind the onset of puberty are still elusive. Assuming a connection between IUGR and pubertal development, parallels can be drawn between hypotheses on the longterm consequences of IUGR and hypotheses on the initiation of puberty. For example, the somatometer concept proposes a role for fat mass in the initiation of puberty, which is compatible with the hypothesis on non-skeletal catch-up growth after IUGR. The debate on the origins of puberty and the role of IUGR mainly focuses on nature and nurture. Judgmentally, studies in mono- and dizygotic twins discordant for birth weight may be of particular help.

Prenatal Influence of Ischemia-Hypoxia-Induced Intrauterine Growth Retardation on Brain Development and Behavioral Activity in Rats

The effects of intrauterine growth retardation (IUGR) on brain histological or functional development were examined in rats. IUGR was induced by ligating the bilateral uterine arteries at day 17 of pregnancy. On day 22 of pregnancy, cesarean section was performed, and pups with a birth weight of <2 SD of the mean birth weight of control pups were regarded as IUGR rats. Morphological changes of the brain were studied by Nissl’s staining at different timepoints during prenatal and postnatal periods. For behavioral study, an open-field test was performed at 5, 7 and 10 weeks after birth. Histological studies showed the migration disorder of the neurons in the cerebral cortex from embryonic day 17 to postnatal day (PD) 49. The open-field test revealed locomotor disturbance at PD49 in male IUGR rats, but not in female IUGR rats or control rats. It is concluded that IUGR due to antenatal ischemia-hypoxia causes morphological changes in the central nervous system, and induces behavioral impairment, particularly in male rats.

Lack of effect of protein deprivation-induced intrauterine growth retardation on behavior and corticosterone and growth hormone secretion in adult male rats: a long-term follow-up study.

To further define the neuroendocrine consequences of intrauterine growth retardation (IUGR), we have used a rat model of maternal protein restriction throughout pregnancy to examine the pattern of corticosterone and GH secretion under basal conditions and in response to psychological stress in male offspring at 4, 9, and 18 months of age. The findings were correlated with studies of behavioral activity. Despite a consistent reduction in birth weight and failure of catch-up growth, there were no significant differences in GH secretory profiles between IUGR and control rats at any age. We were unable to demonstrate a difference in the number, amplitude, length, or area of corticosterone secretory pulses between control and IUGR animals; although again, there was a significant decrease with age. The mean peak plasma concentration of corticosterone in response to a noise stress also declined with age but was unaffected by IUGR. There were no consistent, statistically significant differences in behavioral responses between normal control and IUGR animals or between groups of animals at different ages. These results do not, therefore, support the presence of major functional abnormalities in either GH or corticosterone secretory responses in adult male rats subjected to IUGR.

Food intake and the kidney: The right amounts at the right times

Food intake and the kidney: The right amounts at the right times

Turner’s syndrome: A growing concern

Turner’s syndrome: A growing concern

Endocrine regulation and extended follow up of longitudinal growth in intrauterine growth-retarded rats.

Bilateral uterine artery ligation in late gestation was performed in pregnant dams in order to determine the effects of intrauterine growth retardation (IUGR) on long-term postnatal somatic growth and the GH neuroendocrine axis in the adult female and male rat. Body weight (BW), nose-anus length (NAL) and tail length (TL) were recorded at regular intervals in both the IUGR and control (CON) offspring until the age of 93 days. Spontaneous 6-h GH secretory profiles and serum IGF-I were determined around the age of 100 days in both the IUGR and the CON group. No catch-up growth in BW, NAL or TL was observed in young adult male IUGR rats. Female IUGR rats did catch up in NAL beyond the age of 57 days and in TL before weaning, but did not catch up at any time in BW. Spontaneous 6-h GH secretory profiles in female and male IUGR rats at a mean age of 100+/-4 days were similar to their controls at a mean age of 101+/-4 days. Overall median 6-h rat GH plasma concentrations, rat GH peak amplitude, number of rat GH peaks and sum of peak area were not significantly different. Median serum IGF-I levels in young adult female and male IUGR rats showed no difference when compared with their respective controls. These results demonstrate that IUGR, after bilateral uterine artery ligation in late gestation, leads to incomplete BW catch-up growth in young adult rats of both sexes with physiological GH/IGF-I secretion, suggesting intrauterine modulation of tissue responsiveness to GH and IGF-I. Female IUGR rats do catch up in NAL and TL, developing disturbed body proportions.

Insulin resistance early in adulthood in subjects born with intrauterine growth retardation.

In a case-control study that investigated the effect of intrauterine growth retardation (IUGR) on glucose homeostasis, 20-yr-old adults born with IUGR were shown to be hyperinsulinemic in an oral glucose tolerance test, suggestive of insulin resistance. The aim of this study was to ascertain the decreased insulin sensitivity in young IUGR-born adults compared to that in controls. We studied 26 IUGR-born subjects and 25 controls, aged 25 yr. Insulin sensitivity was assessed by peripheral glucose uptake and monitoring free fatty acid (FFA) concentrations under euglycemic hyperinsulinemic clamp. The percent body fat was significantly higher in the IUGR group (27.2 +/- 7.6% vs. 22.0 +/- 7.3%; P = 0.02), contrasting with comparable body mass index in both groups. Insulin-stimulated glucose uptake was significantly lower in IUGR-born subjects than in controls (6.7 +/- 2.9 vs. 8.0 +/- 1.9 mg/kg fat-free mass x min; P = 0.05), and the difference remained significant after adjustment for body mass index, total body fat, or waist to hip ratio. In IUGR-born subjects, insulin-stimulated FFA suppression correlated significantly with peripheral glucose uptake (r2 = 0.23; P = 0.02). First phase insulin release in the iv glucose tolerance test, adjusted for insulin sensitivity, did not significantly differ between IUGR and control groups (442 +/- 284 vs. 391 +/- 209 pmol/L; P = 0.86). In conclusion, IUGR subjects have decreased insulin-stimulated glucose uptake as early as 25 yr of age without major impairment of insulin secretion. Low glucose uptake is associated with a lesser degree of FFA suppression in adipose tissue, which suggests a role of adipose tissue at an early stage of insulin resistance in these subjects.

510 The effects of intra-uterine growth retardation on wall stress-induced arrhythmia in the working rat heart

510 The effects of intra-uterine growth retardation on wall stress-induced arrhythmia in the working rat heart

Alterations in the offsprings' response to an oral glucose challenge associated with acute maternal malnutrition during late pregnancy

An acutely malnourished pregnant rat model was used to test the effect of intrauterine growth retardation on the subsequent response of the offspring to a loading dose of glucose. Timed-pregnant Harlan-Sprague Dawley rats were given access to only tap water from day 17 through day 19 of their pregnancies (72 hours total). Control mothers had access to lab chow and water throughout their pregnancies. The litters were randomly culled to 4 males and 4 females, whenever possible, and the offspring were given oral glucose tolerance tests at 60, 180 and 360 days of age. At 60 and 180 days of age, malnourished offspring were glucose intolerant (e.g., at 60 days, control males 60 minute serum [glucose] = 9.3±0.1 mM, [malnourished] = 10.1±0.2; [control females] = 9.6±0.2 versus [malnourished] = 10.5±0.3; (overall P<0.05 for treatment). Plasma insulin levels for the malnourished offspring in response to the glucose load were not significantly different at 0 and 30 minutes after the glucose dose. However, at 60 and 120 minutes after the dose, serum insulin levels were significant lower in the malnourished animals ([control males] = 478±47 pMoles/liter versus 351±34; [control females]=436±54 versus 300±33; p<0.05 for treatment). Thus, the insulin to glucose ratio (pMoles/mM) were markedly decreased at the latter time points (control male ratio=49±3, malnourished=34±3; control female=44±4 versus 29±1; p< 0.05 for treatment). At 360 days of age, both male and female malnourished offspring had blood glucose levels comparable to controls in response to the oral glucose challenge. However, while the insulin levels of the malnourished males were comparable to control values, malnourished female insulin levels were lower at all time points.

Birth weight and renal disease in Pima Indians with type 2 diabetes mellitus.

Congenital retardation of renal development may increase the risk of renal disease, and this risk may be enhanced by diseases, such as diabetes, that damage the kidney. In this study, the prevalence of urinary albumin excretion, determined in 308 Pima Indians with type 2 diabetes, was 63% in subjects with low birth weight (<2,500 g), 41% in those with normal birth weight (2,500-4,499 g), and 64% in those with high birth weight (> or =4,500 g). When examined as a continuous variable by generalized additive logistic regression, birth weight had a U-shaped association with the prevalence of elevated urinary albuminuria (p = 0.04) after adjustment for age, sex, duration of diabetes, glycosylated hemoglobin, and blood pressure. The odds of elevated albuminuria in subjects of low birth weight was 2.3 times (95% confidence interval 0.72-7.2) that in subjects of normal birth weight, and the odds in subjects of high birth weight was 3.2 times (95% confidence interval 0.75-13.4) as high. Sixty-four percent of the subjects with high birth weight and none of those with low birth weight were offspring of diabetic mothers. After maternal diabetes during pregnancy was controlled for, the odds of elevated albuminuria in subjects of high birth weight was no longer higher (odds ratio = 1.0, 95% confidence interval 0.22-4.9). The higher prevalence of elevated albuminuria in diabetic Pima Indians with high birth weight may be due to intrauterine diabetes exposure, whereas the higher prevalence in those with low birth weight may be due to the effects of intrauterine growth retardation.

Effects of intrauterine growth retardation and prematurity on spirometric flow values and lung volumes at school age in twin pairs.

Lung volumes and pulmonary expiratory flow values were investigated in 67 children from multiple pregnancies (30 twins, one set of triplets, one set of quadruplets) at the age of 7-15 years. At birth, 30 of 67 children (44%) had intrauterine growth retardation (IUGR, birth weight <-2 SD or birth weight difference between twin-pairs >1.3 SD). The median gestational age was 35 weeks (range, 28-38 weeks), and the median birth weight was 2,050 g (800-3,150 g). Lung functions were measured with a heated pneumotachograph. Data were standardized using height-based reference equations. No differences were found in lung volumes between children with IUGR and those children who had normal birth weight. Gestational age did not correlate with either airway flow rates or lung volumes. Maximum mid-expiratory flow (FEF50) did not correlate with standardized birth weight or with gestational age. In discordant twin pairs, the IUGR twins had significantly lower FEF50 than their normal birth weight counterparts (p=0.03, Z=-2.13). In the whole study group (67 children), children with IUGR had significantly lower FEF50 than children with normal birth weight (p=0.04; CI, 0.3-19.9). We propose that IUGR has the most pronounced effect on the growth of airways, and no detectable influence on lung volumes. This study confirms the crucial effect of appropriate intrauterine growth on subsequent growth on pulmonary airways.

Effects of intrauterine growth retardation and prematurity on spirometric flow values and lung volumes at school age in twin pairs

Lung volumes and pulmonary expiratory flow values were investigated in 67 children from multiple pregnancies (30 twins, one set of triplets, one set of quadruplets) at the age of 7–15 years. At birth, 30 of 67 children (44%) had intrauterine growth retardation (IUGR, birth weight <−2 SD or birth weight difference between twin-pairs >1.3 SD). The median gestational age was 35 weeks (range, 28–38 weeks), and the median birth weight was 2,050 g (800–3,150 g). Lung functions were measured with a heated pneumotachograph. Data were standardized using height-based reference equations. No differences were found in lung volumes between children with IUGR and those children who had normal birth weight. Gestational age did not correlate with either airway flow rates or lung volumes. Maximum mid-expiratory flow (FEF50) did not correlate with standardized birth weight or with gestational age. In discordant twin pairs, the IUGR twins had significantly lower FEF50 than their normal birth weight counterparts (p = 0.03, Z = −2.13). In the whole study group (67 children), children with IUGR had significantly lower FEF50 than children with normal birth weight (p = 0.04; CI, 0.3–19.9). We propose that IUGR has the most pronounced effect on the growth of airways, and no detectable influence on lung volumes. This study confirms the crucial effect of appropriate intrauterine growth on subsequent growth on pulmonary airways. Pediatr Pulmonol. 1998; 25:367–370. © 1998 Wiley-Liss, Inc.

Effect of Intrauterine Growth Retardation on the Clinical Course and Prognosis of IgA Glomerulonephritis in Children

Intrauterine growth retardation (IUGR) resulting in a reduced number of nephrons is one of the nonimmune mechanisms that have been recently proposed as contributing to the progression of renal diseases. The purpose of our study was to determine whether IUGR has any effect on the clinical course and prognosis of IgA glomerulonephritis (IgA GN) in children. Fifty children with biopsy-proven IgA GN, who were followed for at least 3 years, were included. Six of the 50 children (12%) had signs of IUGR at birth, defined as birth weight below the 10th percentile for gestational age. There were no significant differences in initial clinical presentation between children with IUGR and those without IUGR. However, in kidney biopsy specimens, we found a significantly higher mean percentage of sclerotic glomeruli in children with IUGR than in those without IUGR (33 vs. 13%, p < 0.015). At the end of the follow-up period, we observed a significantly higher incidence of arterial hypertension in children with IUGR than in those without IUGR (50 vs. 11%, p < 0.05). Other differences between the two groups of children were not statistically significant. In conclusion, our study demonstrated an increased risk of the development of arterial hypertension and glomerulosclerosis in children with IgA GN who had suffered from IUGR with a birth weight below the 10th percentile for gestational age. IUGR may therefore help to identify early in the course of IgA GN those children who are at higher risk of an unfavorable course.

Ontogeny of Leptin in Human Fetuses and Newborns: Effect of Intrauterine Growth Retardation on Serum Leptin Concentrations

Ontogeny of Leptin in Human Fetuses and Newborns: Effect of Intrauterine Growth Retardation on Serum Leptin Concentrations

Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth retardation on serum leptin concentrations.

The aim of this study was to investigate the ontogeny of serum leptin concentrations during the second half of gestation and at birth in small for gestational age and normal fetuses and newborns. Serum leptin concentrations were measured in arterial cord blood of fetuses (n = 79) and newborns (n = 132), with or without intrauterine growth retardation, at 18-42 weeks gestation. Serum leptin was detectable in fetal cord blood in all subjects as early as 18 weeks gestation. Leptin levels dramatically increased after 34 weeks gestation. In newborns, serum leptin concentrations were positively correlated with body weight (P < 0.001) and body mass index (P < 0.001). Newborns with intrauterine growth retardation had significantly lower serum leptin values (P < 0.001) than those with normal growth, and leptin levels were only positively correlated with body mass index (P < 0.001). These results suggest that the development of adipose tissue and the accumulation of fat mass are the major determinants of fetal and neonatal serum leptin levels. In addition, a gender difference, with higher leptin concentrations in female fetuses, was observed during the last weeks of gestation and was confirmed at birth regardless of growth status, suggesting that a sexual dimorphism already exists in utero.

Developmental consequences of intrauterine growth retardation

Intrauterine growth retardation increases the risks to subsequent functioning among low birthweight children, but the quality of the caretaking environment may influence the impact of these risks. This prospective report examined the consequences of intrauterine growth retardation, neonatal medical risk, and environmental risk for attentional difficulties during early childhood. The developmental status of small-for-gestational-age (SGA) children was within the normal range during infancy but was significantly poorer than that of appropriate-for-gestational-age (AGA) children. Among SGA children, neonatal illness and prematurity had differential influences on childhood attentional difficulties. Intrauterine growth retardation interacted with the quality of the environment to influence the child's ability to sustain attention and inhibit impulsive responses in a task situation. For both SGA and AGA children, the effect of environmental risk was manifested in hyperactive behaviors in the home context.

Metabolic consequences of intrauterine growth retardation.

Epidemiological studies have revealed strong and reproducible links between indices of poor fetal, and possibly infant, growth and susceptibility to the development of glucose intolerance and insulin resistance syndrome in adult life. The 'thrifty phenotype' hypothesis has been proposed to explain these associations. Key features of the hypothesis are: (i) intrauterine growth retardation has a nutritional basis and the resulting altered fetal environment permanently alters the development and metabolic functions of organs: (ii) these alterations are beneficial to survival in a poor nutritional environment, but may lead to diseases such as non-insulin-dependent diabetes mellitus if nutrition is abundant and obesity occurs in adult life. Tests of this hypothesis in an animal model in which pregnant and/or lactating rats were fed a diet with a reduced protein content have shown that liver metabolism in the offspring is permanently altered despite their being weaned onto a normal diet. The longevity of male offspring may be significantly increased or decreased depending on whether growth retardation is restricted to the period of suckling or pregnancy, respectively. The latter finding raises questions about potentially detrimental effects of 'catch-up' growth.

Long-term effects of intrauterine growth retardation.

Intrauterine growth retardation (IUGR) was studied both after experimental induction in rats and spontaneously occurring in man. The growth-retarded rat pups were compared to appropriately grown litter mates with developmental and behavioural tests at 50 and 90 days of age. Female rats exhibited no differences between growth-retarded and control rats but growth-retarded male rats had poor performance at 50 but not at 90 days compared to male controls. In the patient study 25 growth-retarded babies were compared with 21 appropriately grown controls. The growth-retarded babies had delayed latency periods of the visual evoked potentials at term and 6 weeks later, and at follow-up (18 months) demonstrated significantly more developmental and behavioural problems than the control group.