Cause Of Intrauterine Growth Retardation Research Articles

Uteroplacental Insufficiency Causes Microbiota Disruption and Lung Development Impairment in Growth-Restricted Newborn Rats.

Preclinical studies have demonstrated that intrauterine growth retardation (IUGR) is associated with reduced lung development during the neonatal period and infancy. Uteroplacental insufficiency (UPI), affecting approximately 10% of human pregnancies, is the most common cause of IUGR. This study investigated the effects of UPI on lung development and the intestinal microbiota and correlations in newborn rats with IUGR, using bilateral uterine artery ligation to induce UPI. Maternal fecal samples were collected on postnatal day 0. On postnatal days 0 and 7, lung and intestinal microbiota samples were collected from the left lung and the lower gastrointestinal tract. The right lung was harvested for histological assessment and Western blot analysis. Results showed that UPI through bilateral uterine artery ligation did not alter the maternal gut microbiota. IUGR impaired lung development and angiogenesis in newborn rats. Moreover, on postnatal day 0, the presence of Acinetobacter and Delftia in the lungs and Acinetobacter and Nevskia in the gastrointestinal tract was negatively correlated with lung development. Bacteroides in the lungs and Rodentibacter and Romboutsia in the gastrointestinal tract were negatively correlated with lung development on day 7. UPI may have regulated lung development and angiogenesis through the modulation of the newborn rats’ intestinal and lung microbiota.

Effectiveness of nutrition education intervention on maternal nutritional knowledge among women of childbearing age in Ikenne local government area of Ogun State, Nigeria

Background: Nutrient inadequacy during childbearing age and pregnancy is a major cause of intrauterine growth retardation of the foetus leading to other long-term health problems such as non-communicable diseases in later years. More so, child malnutrition and mortality can be majorly attributed to improper infant and young child feeding practices.
 Objective: This study was carried out to assess the effectiveness of nutrition education intervention on maternal nutritional knowledge among women of childbearing age in Ikenne Local Government Area of Ogun State.
 Materials and Method: A descriptive cross-sectional research design was employed for this study and 115 women of childbearing age were selected using simple random sampling technique. Data were collected using a validated questionnaire developed from the “Infant and Young Child Feeding Practices” nutrition education handbook by United Nations Children’s Fund (UNICEF) which was administered pre and post the nutrition education. Data were vetted, coded and subjected to analysis using Statistical Package for Social Sciences (SPSS) version 21.0. Tests were statistically significant at p ≤ 0.05.
 Results: Below average (42.6%) of the respondents had good nutritional knowledge on breastfeeding, 42.6% had average on complementary feeding, while majority (61.8%) had good knowledge on health practices in the pre-test. The post-intervention test revealed significant improvement in their knowledge where 74.8%, 74.0% and 77.4% had good nutritional knowledge on breastfeeding, complementary feeding and health practices respectively. Testing the effectiveness of the nutrition education intervention, there was a significant difference between the pre and post nutritional knowledge test scores (p-0.00).
 Conclusion: The study population had an average knowledge on breastfeeding and complementary feeding before the nutrition education intervention. The post-education tests result showed improvements on their knowledge from average to good on all the practices. This shows that the nutrition education was effective in improving their maternal nutritional knowledge.

Effects of palmitic acid and eicosapentaenoic acid on angiogenesis of porcine vascular endothelial cells.

Restricted placental angiogenesis is an important cause of intrauterine growth retardation in piglets. During pregnancy, sow obesity can result in an increase in placental lipid deposition, subsequently inhibiting placental angiogenesis and fetal development. However, the effect of different types of fatty acids on placental angiogenesis is still unclear. Trophoblast cells and vascular endothelial cells constitute two important types of placental tissue. In this study, we used palmitic acid (C16:0) and eicosapentaenoic acid (C20:5, n‐3), respectively, to treat porcine trophectoderm cells (pTr2) and porcine iliac artery endothelial cells (PIEC) to study the effects of saturated fatty acids and n‐3 polyunsaturated fatty acids (PUFAs) on placental angiogenesis in vitro. We found that C16:0 caused significant cytotoxicity in pTr2 and PIEC (p < 0.01) and inhibited the proliferation and migration of PIEC (p < 0.01), whereas C20:5 treatment exhibited very low cytotoxicity and minimal inhibition of cellular proliferation. Meanwhile, a low concentration of C16:0 had no effect on the tube formation in PIEC, whereas C20:5 significantly promoted tube formation of PIEC (p < 0.01). These results suggested that saturated fatty acids and n‐3 PUFAs had different effects on placental angiogenesis. As essential functional fatty acid, n‐3 PUFA might be effective measure in alleviating the placental lipotoxicity caused by sow obesity during pregnancy.

Morpho-Histological Study of Placentae from Pregnancies Complicated by Anemia

Background: The placenta is an important organ that acts as a conduit for transporting substances from the mother to the fetus and vice versa. It performs many functions and is intimately related to both the mother and the fetus. Anemia is a leading disorder of pregnancy and is seen to effect >65% of pregnant women in India. It is also a known cause of intra-uterine growth retardation, preterm deliveries, low-birth-weight deliveries, etc. Objective: The aim is to study and compare the morphometric and histological changes seen in placentae from normal and anemic mothers. Methods: This study was done in the Department of Anatomy of Shri Ram Murti Smarak Institute of Medical Sciences and Research, Bareilly, Uttar Pradesh, India. One hundred and fifty placentae were collected, 75 each from normal and anemic mothers. A thorough morphometric and histological study of the placentae was done, and the results were recorded. Results: It was observed that the mean weight, diameter, circumference, and chorionic plate area of the placentae from anemic mothers was significantly reduced in comparison to the controls. Histological study showed that there was a significant increase in pathological changes such as syncytial knots, fibrinoid necrosis, calcification, and medial coat proliferation of blood vessels in samples obtained from placentae of anemic mothers in comparison to the controls. Conclusion: It was concluded from this study that maternal anemia has significant consequences on the developing placenta. These morphometric and microscopic changes in placental structure can in turn reduce its function, thus having an adverse effect on fetal outcome.

Effect of Curcumin on Growth Performance, Inflammation, Insulin level, and Lipid Metabolism in Weaned Piglets with IUGR.

The possible causes of intrauterine growth retardation (IUGR) might stem from placental insufficiency, maternal malnutrition, inflammation in utero, and other causes. IUGR has had an adverse influence on human health and animal production. Forty weaned piglets with normal birth weights (NBWs) or IUGR were randomly divided into four treatments groups: NBW, NC (NBW with curcumin supplementation), IUGR, and IC (IUGR with curcumin supplementation) from 26 to 50 d. Levels of cytokines, glucose, and lipid metabolism were evaluated. IUGR piglets showed slow growth during the experiment. Piglets with IUGR showed higher levels of serum pro-inflammatory cytokines, insulin resistance, and hepatic lipid accumulation. Curcumin supplementation reduced the production of serum pro-inflammatory cytokines, attenuated insulin resistance and hepatic triglyceride, and enhanced the hepatic glycogen concentrations and lipase activities of IUGR piglets. The hepatic mRNA expressions of the insulin-signaling pathway and lipogenic pathway were influenced by IUGR and were positively attenuated by diets supplemented with curcumin. In conclusion, IUGR caused slow growth, insulin resistance, and increased hepatic lipid levels. Diets supplemented with curcumin improved growth, attenuated insulin resistance, and reduced lipid levels in the liver by regulating the hepatic gene expressions of the related signaling pathway in IUGR piglets.

Hypoxia-inducible factor prolyl-4-hydroxylation in FOXD1 lineage cells is essential for normal kidney development

Hypoxia in the embryo is a frequent cause of intra-uterine growth retardation, low birth weight, and multiple organ defects. In the kidney, this can lead to low nephron endowment, predisposing to chronic kidney disease and arterial hypertension. A key component in cellular adaptation to hypoxia is the hypoxia-inducible factor pathway, which is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3. In the adult kidney, PHD oxygen sensors are differentially expressed in a cell type-dependent manner and control the production of erythropoietin in interstitial cells. However, the role of interstitial cell PHDs in renal development has not been examined. Here we used a genetic approach in mice to interrogate PHD function in FOXD1-expressing stroma during nephrogenesis. We demonstrate that PHD2 and PHD3 are essential for normal kidney development as the combined inactivation of stromal PHD2 and PHD3 resulted in renal failure that was associated with reduced kidney size, decreased numbers of glomeruli, and abnormal postnatal nephron formation. In contrast, nephrogenesis was normal in animals with individual PHD inactivation. We furthermore demonstrate that the defect in nephron formation in PHD2/PHD3 double mutants required intact hypoxia-inducible factor-2 signaling and was dependent on the extent of stromal hypoxia-inducible factor activation. Thus, hypoxia-inducible factor prolyl-4-hydroxylation in renal interstitial cells is critical for normal nephron formation.

Морфофункціональні зміни в плаценті у вагітних при затримці росту плода

The objective: to reveal morphofunctional changes in the placenta of pregnant with intrauterine growth retardation of different severity. Patients and Methods. The study included 100 pregnant (from 23 to 40 weeks of gestation). The main group consisted of 80 pregnant women with intrauterine growth retardation of different severity. The control group consisted of 20 women with physiological course of pregnancy. The patients of the main group were divided into three clinical groups regarding intrauterine growth retardation staging. Group I included 38 pregnant with stage 1 IUGR, 22 pregnant women with stage II IUGR were in group 2 and 20 pregnant with stage 3 IUGR – in group III. Revealing intrauterine growth retardation in pregnant women, the form and the stage, as well as violations of the uteroplacental and fetal blood flow was based on the results of ultrasound Doppler studies. The comparison of fetometry results and normative indices of the definite duration of gestation was made to diagnose intrauterine growth retardation. For morphological studies full-thickness placenta tissue sections were cut from a central, paracentral and areas after the separation of the placenta. From the marginal areas there were cut tissue sections with membranes. From umbilical cord there were cut two sections at 2 cm distance from the insertion of the umbilical cord to the placenta and on the opposite side. The tissue samples were fixed with 10% neutral formalin and embedded in paraffin; histologic sections were stained by hematoxylin-eosin. We paid attention to the severity of compensatory adaptive and involutory destructive reactions in the placenta. The maturity of villous tree was evaluated using the criteria for Voloshchuk’s classification of villous tree maldevelopment. The variational methods were used to make the statistical analysis of outcomes by standard licensed computer programs: STATISTICA 6.0, Microsoft Excel, ANOVA «Statistica». Differences among values were considered statistically significant if p&lt;0.05. Results. The morphology of the placenta in case of intrauterine growth retardation is characterized by a high incidence of uteroplacental blood flow violations. The changes are mainly caused by insufficient maternal blood in intervillous space. The most common morphological manifestations of the violated blood flow in intervillous space were heart attacks, afunctional areas, successive narrowing and thrombosis of intervillous space. The incidence of blood flow violations in intervillous space is growing with increased severity of fetal growth retardation. Conclusions. Placental insufficiency due to morphological and functional changes in the placenta is the leading cause of intrauterine growth retardation and fetal hypoxia. It develops as a result of fetal and placenta combined reaction to various disorders in the mother’s body. The incidence of blood flow violations in intervillous space is growing with increased severity of fetal growth retardation. Key words: intrauterine growth retardation, pregnant, placenta, placental insufficiency, morphofunctional changes.

Intra-uterine Growth Retardation as a Risk Factor of Postnatal Metabolic Disorders.

Intra-uterine growth retardation (IUGR) represents one of the major problems in perinatal medicine. IUGR is one of main causes of perinatal mortality and morbidity. A huge number and variety of established and possible causes of IUGR have been described. There are currently no data about effective treatment of this fetal condition. IUGR has been described to be strictly involved in fetal programming. Fetal programming is the general idea, which tells us how during development of the embryo and fetus significant physiological parameters can be shaped by environmental events. A link between the intra-uterine growth retardation and the risk of developing type 2 diabetes, obesity and cardiovascular disease postnatally has been well documented. The aim of this paper is to present an overview of the current knowledge of IUGR effects on development of hypertension and cardiovascular diseases, impact on insulin secretion and resistance, diabetes mellitus and metabolic syndrome. The influence of intrauterine growth retardation on predisposition to obesity and adipose dysfunction was also described.

Intrauterine Growth Retardation (IUGR) as a Novel Condition of Insulin-Like Growth Factor-1 (IGF-1) Deficiency.

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone with several biological activities, such as proliferation, mitochondrial protection, cell survival, tissue growth and development, anti-inflammatory, antioxidant, antifibrogenic and antiaging. This hormone plays an important role in embryological and postnatal states, being essential for normal foetal and placental growth and differentiation. During gestation, the placenta is one of the major sources of IGF-1, among other hormones. This intrauterine organ expresses IGF-1 receptors and IGF-1 binding proteins (IGFBPs), which control IGF-1 activities. Intrauterine growth restriction (IUGR) is the second most frequent cause of perinatal morbidity and mortality, defined as the inability to achieve the expected weight for gestational age. Different studies have revealed that IUGR infants have placental dysfunction and low circulating levels of insulin, IGF-1, IGF-2 and IGFBPs. Such data suggest that IGF-1 deficiency in gestational state may be one of the major causes of foetal growth retardation. The aim of this review is to study the epidemiology, physiopathology and possible causes of IUGR. Also, it intends to study the possible role of the placenta as an IGF-1 target organ. The purpose is to establish if IUGR could be considered as a novel condition of IGF-1 deficiency and if its treatment with low doses of IGF-1 could be a suitable therapeutic strategy.

Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring

Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible.

Developmental programing: impact of testosterone on placental differentiation.

Gestational testosterone treatment causes maternal hyperinsulinemia, intrauterine growth retardation (IUGR), low birth weight, and adult reproductive and metabolic dysfunctions. Sheep models of IUGR demonstrate placental insufficiency as an underlying cause of IUGR. Placental compromise is probably the cause of fetal growth retardation in gestational testosterone-treated sheep. This study tested whether testosterone excess compromises placental differentiation by its androgenic action and/or via altered insulin sensitivity. A comparative approach of studying gestational testosterone (aromatizable androgen) against dihydrotestosterone (non-aromatizable androgen) or testosterone plus androgen antagonist, flutamide, was used to determine whether the effects of testosterone on placental differentiation were programed by its androgenic actions. Co-treatment of testosterone with the insulin sensitizer, rosiglitazone, was used to establish whether the effects of gestational testosterone on placentome differentiation involved compromised insulin sensitivity. Parallel cohorts of pregnant females were maintained for lambing and the birth weight of their offspring was recorded. Placental studies were conducted on days 65, 90, or 140 of gestation. Results indicated that i) gestational testosterone treatment advances placental differentiation, evident as early as day 65 of gestation, and culminates in low birth weight, ii) placental advancement is facilitated at least in part by androgenic actions of testosterone and is not a function of disrupted insulin homeostasis, and iii) placental advancement, while helping to increase placental efficiency, was insufficient to prevent IUGR and low-birth-weight female offspring. Findings from this study may be of relevance to women with polycystic ovary syndrome, whose reproductive and metabolic phenotype is captured by the gestational testosterone-treated offspring.

Severe Short Stature Caused by Novel Compound Heterozygous Mutations of the Insulin-Like Growth Factor 1 Receptor (IGF1R)

IGF-I, essential for normal human growth in utero and postnatally, mediates its effects through the IGF-I receptor (IGF1R). More than nine heterozygous mutations, including one compound heterozygous mutation, of the IGF1R gene have been reported in patients with varying degrees of intrauterine and postnatal growth retardation. The objective of the study was the analysis of the IGF1R gene in a short-statured patient. The male patient, with a height of -5.91 sd score (aged 20.3 yr), had consistently elevated circulating serum concentrations of IGF-I. A diagnosis of antibody-negative insulin-requiring diabetes was made at age 14 yr. His deceased sister was also severely short statured (-3.75 sd score). The patient and his sister carried novel, compound heterozygous IGF1R missense mutations, E121K (exon 2) and E234K (exon 3), inherited from the mother and father, respectively. In vitro reconstitution studies demonstrated that neither the E121K nor E234K mutation affected IGF1R prepeptide expression, but levels of the proteolytically cleaved α- and β-subunit were consistently low. As a consequence, each IGF1R variant exhibited significantly reduced IGF-I-induced signal transduction. Correlating to these studies, expression of functional IGF1R and the IGF-I-induced activation of the IGF1R pathway were markedly reduced in the primary dermal fibroblasts established from the patient. Only the second compound heterozygous IGF1R mutations to be identified, the p.E121K/E234K variant is the cause of intrauterine growth retardation and the most severe postnatal growth failure described to date in a patient with IGF1R defects. Whether the mutant IGF1R also contributes to the diabetic phenotype, however, remains to be determined.

High efficacy of anti DBL4ɛ-VAR2CSA antibodies in inhibition of CSA-binding Plasmodium falciparum-infected erythrocytes from pregnant women

Malaria during pregnancy is a major cause of intra-uterine growth-retardation and infant death in sub-Saharan Africa. Ideally, this could be prevented by a vaccine delivered before the first pregnancy. Antibodies against domain DBL4ɛ from VAR2CSA has been shown to inhibit adhesion of laboratory isolates to the placental receptor chondroitin sulfate A. In this study, the binding inhibitory efficacy of IgG elicited by two different DBL4ɛ recombinant proteins was tested on a panel of fresh clinical isolates from pregnant women living in Benin and Tanzania. The most promising recombinant protein elicited antibodies with similar efficacy as pooled plasma from immune multi-gravid African women.

Physical Growth and Development of the Malnourished Child: Contributions from 50 years of Research at INCAP

This paper reviews the main findings and policy implications of 50 years (1949-1999) of research conducted by INCAP on growth and development. Topical areas reviewed include a) maternal size and birthweight and the causes of intrauterine growth retardation (IUGR), b) patterns and causes of postnatal growth retardation, c) the relative importance of genetics and the environment in explaining differences in growth among populations, d) the implications of being small, for both children and adults, e) bone growth and maturation and dental development, f) menarche, and g) methodological contributions such as anthropometric reference data, quality control of data collection, development of risk indicators and use of anthropometry in nutrition surveillance systems. Key contributions to knowledge by INCAP include a) characterization of growth failure and maturational delays as mainly occurring during the intrauterine period and the first 3 years of life b) clarification of the role of small maternal size and of inadequate dietary intakes during pregnancy as major causes of intrauterine growth failure, c) evidence that diarrheal diseases and poor dietary intakes are the principal causes of growth failure in early childhood, d) demonstration that environmental factors related to poverty, and not genetic or racial ancestry, account for most of the differences in growth between populations, e) evidence that growth failure predicts functional impairment in the child as well as in the adult andf) demonstration that nutrition interventions are effective in preventing growth failure and its consequences, if targeted to needy women and young children. INCAP's work has contributed knowledge that has informed and improved policies and programs aimed at overcoming maternal and child undernutrition and promoting optimal growth and development.

Pulmonary Vascular Endothelial Growth Factor Expression and Disaturated Phospholipid Content in a Chicken Model of Hypoxia-Induced Fetal Growth Restriction

Background: Prenatal hypoxia is an important cause of intrauterine growth retardation that affects fetal lung maturation, although previous studies have rendered conflicting results. The fetal chicken model allows the study of the isolated effects of hypoxia during development. Objectives: We hypothesized that prenatal hypoxia would differentially affect surfactant synthesis, depending on timing and duration of hypoxia. Pulmonary vascular endothelial growth factor (VEGF) expression was analyzed as a possible link between oxygen sensing and surfactant production. Methods: Fertilized White Leghorn eggs were incubated in normoxia, hyperoxia (60% O₂) from day 15 or hypoxia (15% O₂) from either day 6 or day 15 of incubation. Whole lung disaturated phospholipids (DSPL) and mRNA expression of VEGF isoforms were quantified at day 16 and 19. Results: Lung DSPL content increased approximately threefold between day 16 and 19 in control animals. Both hypoxia and hyperoxia from day 15 significantly increased DSPL content at day 19 versus control (103 ± 22 and 116 ± 18 vs. 81 ± 15 µg/mg protein, p < 0.01 and p < 0.001, respectively), while long-term hypoxia tended to decrease DSPL content (65 ± 17 µg/mg protein, p = 0.056). No differences in DSPL content were observed at day 16. Short-term hypoxia transiently up-regulated VEGF146 1.5-fold at day 16 (p < 0.05). A similar trend was observed for VEGF122 (p = 0.058) and VEGF190 (p = 0.08), while no differences were present at day 19. Conclusions: Both prenatal hypoxia and hyperoxia induced during critical windows of lung development differentially modulate surfactant synthesis. Our data support the concept that fetal oxygen tension is a key signal in the regulation of the surfactant system.

Three‐dimensional assessment of the morphology of the umbilical artery in normal and pre‐eclamptic placentas

Pre-eclampsia is one of the main causes of intrauterine growth retardation. Although there are many studies performed in this setting showing the course of the umbilical vessels within the umbilical cord along with its structural changes, studies are lacking with regard to intraplacental vasculature and its structural changes. We investigated whether the vascular pattern differed in preeclamptic placentas in terms of intraplacental course and morphometry of the umbilical artery by using vascular corrosion cast technique. Furthermore, cross-sections taken from umbilical artery branches at different levels within the placenta, were examined with both light and scanning electron microscopy (SEM). Vascular corrosion casts generated in both pregnancy groups should be defined with the main umbilical artery divided into 2-4 primary branches. No significant difference was seen between normal and pre-eclamptic groups regarding the diameters of primary and secondary branches and the number of cotyledons contained (P > 0.05). However, microscopic studies demonstrated expanded intervillous spaces in the placentas of pre-eclamptic pregnancies. Under SEM, distortion on the endothelial surface of the umbilical artery and an increase in vessel diameter and wall thickness have been determined in pre-eclamptic placentas. Furthermore, the branching pattern and changes affecting the endothelial surface of the umbilical artery have been shown three-dimensionally in pre-eclamptic placentas, using corrosion cast technique and SEM, respectively. While microscopic findings were consistent with the Doppler ultrasonography findings, namely higher systole/diastole ratio and increased resistance (RI) and pulsatile (PI) index in the umbilical artery, no clear morphometric change has been observed.

Identification of mutations in CUL7 in 3-M syndrome

Intrauterine growth retardation is caused by maternal, fetal or placental factors that result in impaired endovascular trophoblast invasion and reduced placental perfusion. Although various causes of intrauterine growth retardation have been identified, most cases remain unexplained. Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7). CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination. Using deletion analysis, we found that CUL7 uses its central region to interact with the Skp1-Fbx29 heterodimer. Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1. These results suggest that impaired ubiquitination may have a role in the pathogenesis of intrauterine growth retardation in humans.

Effect of Maternal Malnutrition and Anemia on the Endocrine Regulation of Fetal Growth

Fetal growth retardation is a result of a complex pathology caused by multiple factors of fetal, placental, and maternal origin. Hormones and growth factors released as a result of maternal‐fetal physiological interactions play an importance role in fetal well being and fetal outcome. Intrauterine Growth Retardation (IUGR) is associated with significant perinatal and childhood morbidity. It is estimated that 13.7 million infants are born annually with IUGR, comprising 11% of all births in developing countries. Both maternal malnutrition and anemia are associated with various degrees of fetal growth retardation The relationship between decreasing birth weight percentiles and increasing fetal morbidity and mortality has been demonstrated by several investigators and epidemiological studies suggest that IUGR is a significant risk factor for the subsequent development of chronic hypertension, ischemic heart disease, diabetes, and obstructive lung disease in adult life (Barker's Hypothesis). Maternal anemia and/or malnutrition are recognized to be the most frequent cause of IUGR and SGA birth in developing countries like India. In order to investigate adaptive mechanisms by the fetus to overcome the growth disadvantage caused due to maternal nutritional limitations, we examined the quantitative variations in hormonal and growth factor profiles in paired cord blood and maternal samples obtained from neonates born to malnourished and/or anemic mothers. The results of our study show that: 1) The percentage of small for gestational age (SGA) neonates born to malnourished and anemic mothers was significantly higher than those born to mothers who were either malnourished or anemic; 2) Significantly higher levels of GH, PRL, HPL and IGF‐1 were observed in the cord blood of neonates born to malnourished and anemic mothers indicative of an adaptive response on part of the fetus to over come an in‐utero growth disadvantage; 3) The anoxemia‐related fetal perturbations may have unique features that make them distinct from nutrient deficiency‐related IUGR. Thus, these novel observations are relevant to the context of the ongoing scientific debate on Barker's hypothesis.

Endocrine-related causes and consequences of intrauterine growth retardation.

The term intrauterine growth retardation (IUGR) is assigned to newborns born with a birth weight and/or birth length below the tenth percentile for their gestational age. Intrauterine growth retardation is usually due to maternal, fetal factors, or placental insufficiency, while endocrine factors represent just a small minority in its etiology. Main endocrine-related causes of IUGR are disorders in insulin or insulin-like growth factor-I (IGF-I) secretion or action. Newborns with IUGR are at increased risk to develop a metabolic syndrome later in life, namely obesity, arterial hypertension, hypercholesterolemia, cardiovascular disease, impaired glucose tolerance, or diabetes mellitus type 2. This association is the result of the adaptational changes of the fetal endocrine-metabolic mechanisms to the impaired intrauterine milieu to assure survival in the short term. The persistence of these changes after birth can be detrimental in adult life. Furthermore, premature adrenarche, as well as ovarian hyperandrogenism, seem to be associated with IUGR in girls, demonstrating that IUGR may have long-lasting effects on both somatic health and reproductive function. Finally, the intrauterine exposure of the fetus to stressors may affect the individual's ability to face stress in postnatal life. Therefore, if optimization of somatic and psychosocial well-being of the individual is the golden goal of medicine, special attention should be paid to maintain an optimal intrauterine milieu devoid of any stressors with adequate nutrient supply and to reserve ideal psychosocial support to the pregnant woman.

Micronutrients and Fetal Growth

Fetal undernutrition affects large numbers of infants in developing countries, with adverse consequences for their immediate survival and lifelong health. It manifests as intrauterine growth retardation (IUGR), defined as birth weight <10th percentile, which probably underestimates the number failing to achieve full growth potential. Birth weight is a crude measure of the dynamic process of fetal growth and does not capture effects of fetal undernutrition on body composition and the development of specific tissues. The link between maternal nutrition and fetal nutrition is indirect. The fetus is nourished by a complex supply line that includes the mother's diet and absorption, endocrine status and metabolism, cardiovascular adaptations to pregnancy and placental function. Micronutrients are essential for growth, and maternal micronutrient deficiency, frequently multiple in developing countries, may be an important cause of IUGR. Supplementation of undernourished mothers with micronutrients has several benefits but there is little hard evidence of improved fetal growth. However, this has been inadequately tested. Most trials have only used single micronutrients and many were inconclusive because of methodological problems. Several food-based studies (some uncontrolled) suggest benefits from improving maternal dietary quality with micronutrient-dense foods. One trial of a multivitamin supplement (HIV-positive mothers, Tanzania) showed increased birth weight and fewer fetal deaths. Well-conducted randomized controlled trials of adequate sample size and including measures of effectiveness are needed in populations at high risk of micronutrient deficiency and IUGR and should include food-based interventions and better measurements of fetal growth, maternal metabolism, and long-term outcomes in the offspring.