Intrauterine Fetal Growth Retardation Research Articles

Indole-3-carbinol alters placental cytochrome P450 1A1 and P-glycoprotein levels in rats: A potential role in intensifying fetal intrauterine growth-retardation produced by tobacco smoke

To investigate the deleterious effects and possible mechanism of prenatal indole-3-carbinol (I3C) treatment on normal and tobacco-induced intrauterine growth restriction (IUGR) in rats, prenatal development toxicity in rats was studied. Expression of rat placental cytochrome P4501A1 ( CYP1A1) and P-glycoprotein (Pgp), including mdr1a and mdr1b, were detected using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Results showed that prenatal oral I3C had no significant effects on corpora lutea counts, implantation or the number of live, dead and resorbed fetuses in normal rats. Fetal malformations, sex ratio, neonatal body weights and physical developmental indices were also unchanged after prenatal I3C treatment. However, the offspring in the tobacco+I3C (4 mg kg −1) group showed lower average body weights (3.98±0.29 g) than tobacco control (4.48±0.11 g), and body and tail lengths lagged significantly behind those of the tobacco-smoke exposure only group. Expression of placental CYP1A1 mRNA by RT-PCR was not detected in the normal group, but was detected in the I3C, tobacco and tobacco+I3C groups. The level of CYP1A1 mRNA expression in the tobacco+I3C group was higher than in tobacco control. The level of mdr1a mRNA increased significantly in the I3C group when compared to normal control, and no obvious difference was detected between tobacco and tobacco+I3C groups. Expression of mdr1b mRNA was increased in the I3C and tobacco+I3C groups compared to their respective controls. Immunohistochemistry results showed that placental Pgp expression was enhanced in the I3C, tobacco and tobacco+I3C groups when compared to the normal control. The results suggest that prenatal oral I3C had no developmental toxicity but intensified fetal IUGR produced by prenatal tobacco-smoke exposure in rats. Up-regulations of placental CYP1A1 and Pgp by I3C might underlie the toxic mechanism.

Relationship between fetal plasma erythropoietin (EPO) concentration and intrauterine fetal growth retardation

目的 探讨促红细胞生成素(EPO)与宫内生长发育迟缓的关系.方法采用ELISA法对24例小于胎龄儿(SGA)和28例适于胎龄儿(AGA)血中EPO浓度进行定量检测,末梢血涂片经瑞氏染色计数100个白细胞中含有的有核红细胞数(NRBC/100WBC),并根据血常规中的白细胞数计算出有核红细胞的绝对计数(NRBC).同时检测动脉血pH、BE和HCO3-等指标.生后3～5 d进行头部CT检查,以确定神经系统病变情况.结果(1)体重、EPO、NRBC/100WBC、NRBC、pH、BE两组比较 有显著性差异(P＜0.05),两组的RBC、HCO3比较无显著性差异(P＞0.05).(2)经过相关性分析,SGA组的体重与EPO呈显著负相关,r值为-0.470(P＜0.05);AGA组的体重与EPO无相关性,r值为0.128(P＞0.05).(3)EPO分别和NRBC/100WBC、NRBC呈正相关,r值分别为0.642(P＜0.05)和0.595(P＜0.05);EPO分别和BE、HCO3-呈负相关,r值分别是-0.434(P＜0.05)和-0.487(P＜0.05).(4)在SGA组中高水平EPO的患儿预后较差.结论EPO是反映SGA慢性缺氧的理想指标,与预后密切相关。

Gender-Related Changes in Magnetocardiographically Determined Fetal Cardiac Time Intervals in Intrauterine Growth Retardation

Prenatal growth deficiencies as well as gender have been associated with cardiovascular disease in later life. It is also known that the duration of fetal cardiac time intervals (CTI) are dependent on fetal development. The aim of this work was to examine the relationship between fetal CTI in healthy and intrauterine growth retardation (IUGR) fetuses, taking gender into account. A total of 269 magnetocardiograms (MCG) were obtained in 47 healthy and 27 IUGR pregnancies. In each signal-averaged MCG, durations of CTI were determined. Age- and heart rate-corrected values were compared between normal and IUGR fetuses separately with respect to gender. Overall, there was an association between atrial and ventricular conduction times and estimated fetal body weight. In female fetuses, IUGR was associated with shorter P WAVE, PQ segment, PR interval, and QRS complex and longer STT and QT intervals. For males, this was so only for P wave, QRS complex, and STT interval. The shortening of conduction times in IUGR may be explained by reduced cardiac muscle mass associated with lower body weight. On the other hand, the gender-specific differences, particularly in the IUGR fetuses may be due to hormonal factors.

Endocrine regulation in asymmetric intrauterine fetal growth retardation

Objective. The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother.Materials and methods. We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA).Results. (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers.Conclusion. Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary–thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.

Is the immunohistochemical study of the inflammatory infiltrate helpful in distinguishing villitis of unknown etiology from non-specific infection villitis?

Villitis is an important placental lesion, which can be caused by specific maternal infections, e.g. rubella, toxoplasmosis, etc, but most of them are of unknown etiology [1]. The clinical significance of villitis depends on the etiology and severity of fetal infection [2] and may lead to intrauterine fetal death, abortion, malformations and fetal growth retardation. The latter has been the major clinical association of villitis of unknown etiology (VUE) [2e4]. Morphologically, infectious villitis may show no specific features and can masquerade as VUE [5]. Both lesions are characterized by chronic inflammatory cells, mainly macrophages and lymphocytes, in the placental villous stroma [2,5]. There are few immunomorphological studies about the immune cells in infectious villitis as well as in VUE [6e9]. Labarrere et al. [6] described that in placentas with VUE the predominant inflammatory cells were activated macrophages expressing class II major histocompatibility complex antigens and helper T cells. Few CD8C T cells and no B cells were detected in the same lesions [6]. These findings contrast with those in villitis caused by maternal infection by Trypanosoma cruzi (Chagas’ disease), in which CD8C cells outnumbered CD4C T cells [7]. The aim of this study was to analyze whether immunohistochemical study of the inflammatory infiltrate in chronic villitis without specific morphological features could distinguish VUE from infectious villitis. All cases of villitis should be reported, particularly in developing countries, where there is a higher incidence of intrauterine infection [10] and the immunohistochemical study could provide objectivity that conventional histological methods lack.

Ascorbic acid protects against lipopolysaccharide-induced intra-uterine fetal death and intra-uterine growth retardation in mice

Lipopolysaccharide (LPS) has been associated with adverse developmental outcomes including embryonic resorption, intra-uterine fetal death (IUFD), intra-uterine growth retardation (IUGR) and preterm labor. Reactive oxygen species (ROS) mediate LPS-induced developmental toxicity. Ascorbic acid is an antioxidant. In the present study, we investigated the effect of ascorbic acid on LPS-induced IUFD and IUGR in mice. All ICR pregnant mice except controls received an intraperitoneal (75 μg/kg, i.p.) injection of LPS daily on gd 15–17. The experiment was carried out in three different modes. In mode A, the pregnant mice were pretreated with a single dose (500 mg/kg, i.p.) of ascorbic acid before LPS. In mode B, the pregnant mice were administered with a single dose (500 mg/kg, i.p.) of ascorbic acid at 3 h after LPS. In mode C, the pregnant mice were administered with 500 mg/kg (i.p.) of ascorbic acid at 30 min before LPS, followed by additional dose (500 mg/kg, i.p.) of ascorbic acid at 3 h after LPS. The number of live fetuses, dead fetuses and resorption sites was counted on gd 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Results showed that maternally administered LPS significantly increased fetal mortality, decreased fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone. LPS-induced IUFD and IUGR were associated with lipid peroxidation and GSH depletion in maternal liver, placenta and fetal liver. Pre-treatment with ascorbic acid significantly attenuated LPS-induced lipid peroxidation, decreased fetal mortality, and reversed LPS-induced fetal growth and skeletal development retardation. By contrast to pre-treatment, post-treatment with ascorbic acid had less effect on LPS-induced IUFD, although post-treatment significantly attenuated LPS-induced lipid peroxidation and reversed LPS-induced fetal growth and skeletal development retardation. Furthermore, post-treatment with ascorbic acid reduced the protective effects of pre-treatment on LPS-induced IUFD. All these results suggest that pre-treatment with ascorbic acid protected against LPS-induced fetal death and reversed LPS-induced growth and skeletal development retardation via counteracting LPS-induced oxidative stress, whereas post-treatment had less effect on LPS-induced IUFD.

Effect of N-Acetylcysteine on Lipopolysaccharide-Induced Intra-uterine Fetal Death and Intra-uterine Growth Retardation in Mice

Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including embryonic resorption, intra-uterine fetal death (IUFD), intra-uterine growth retardation (IUGR), and preterm delivery. Reactive oxygen species (ROS) have been associated with LPS-induced developmental toxicity. N-acetylcysteine (NAC) is a glutathione (GSH) precursor and direct antioxidant. The present study investigated the effects of NAC on LPS-induced IUFD and IUGR. All pregnant mice except controls were injected with LPS (75 microg/kg, ip) on gestational day (GD) 15-17. NAC was administered in two different modes. In mode A, the pregnant mice were pretreated with two doses of NAC (either 50 plus 25 mg/kg or 200 plus 100 mg/kg) before LPS, one (either 50 or 200 mg/kg) at 12 h before LPS and the other (either 25 or 100 mg/kg) at 15 min before LPS. In mode B, the pregnant mice were administered with two doses of NAC (either 50 plus 25 mg/kg or 200 plus 100 mg/kg) in 24 h, one (either 50 or 200 mg/kg) injected immediately after LPS and the other (either 25 or 100 mg/kg) injected 3 h after LPS. The number of live fetuses, dead fetuses and resorption sites was counted on GD 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were measured and skeletal development was evaluated. Results showed that pretreatment with NAC significantly alleviated LPS-induced fetal mortality and reversed LPS-induced growth and skeletal development retardation. Correspondingly, pretreatment with NAC significantly attenuated LPS-induced elevation in TNF-alpha concentration in maternal serum and amniotic fluid and lipid peroxidation in maternal and fetal livers. By contrast to pretreatment, posttreatment with NAC had no effect on LPS-induced TNF-alpha production and lipid peroxidation. When administered after LPS, NAC did not protect against LPS-induced IUFD and IUGR and in fact aggravated LPS-induced preterm labor. All these results indicate that NAC had a dual effect on LPS-induced IUFD and IUGR. Pretreatment with NAC improves fetal survival and reverses LPS-induced fetal growth and skeletal development retardation, whereas posttreatment with NAC aggravates LPS-induced preterm labor.

Melatonin protects against lipopolysaccharide‐induced intra‐uterine fetal death and growth retardation in mice

Lipopolysaccharide (LPS) has been associated with adverse developmental outcomes, including intra-uterine fetal death (IUFD) and intra-uterine growth retardation (IUGR). However, the exact mechanism for LPS-induced IUFD and IURD remains unclear. LPS stimulates macrophages to generate reactive oxygen species (ROS). Therefore, we hypothesize that ROS may be involved in LPS-induced IUFD and IURD. Melatonin is a powerful endogenous antioxidant. In this study, we investigated the protective effects of melatonin on LPS-induced IUFD and IURD in ICR mice. All pregnant mice except controls received an intraperitoneal (75 microg/kg, i.p.) injection of LPS on gestational day (gd) 15-17. The experiment was carried out in two different modes. In mode A, the pregnant mice received two doses of melatonin within 24 hr, one (5 or 10 mg/kg) injected immediately after LPS and the other (5 or 10 mg/kg) injected at 3 hr after LPS. In mode B, the pregnant mice were pretreated with 10 mg/kg of melatonin 18 hr before LPS and then received two doses of melatonin in 24 hr, one (10 mg/kg) injected immediately after LPS and the other (10 mg/kg) injected 3 hr after LPS. The number of live fetuses, dead fetuses and resorption sites were counted on gd 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Results showed that post-treatments with melatonin significantly attenuated LPS-induced IUFD in a dose-dependent manner. Surprisingly, pre- plus post-treatments with melatonin almost blocked LPS-induced IUFD. In addition, both post-treatments and pre- plus post-treatments with melatonin significantly alleviated LPS-induced decreases in crown-rump and tail lengths and reversed LPS-induced skeletal developmental retardation. However, melatonin had little effect on LPS-induced decrease in fetal weight. Furthermore, pre- plus post-treatments with melatonin significantly attenuated LPS-induced lipid peroxidation in maternal liver. These results indicate that melatonin protects against LPS-induced IURD and IUGR via counteracting LPS-induced oxidative stress.

Erythrocyte Zinc Protoporphyrin Is Elevated With Prematurity and Fetal Hypoxemia

To examine the utility of red blood cell (RBC) zinc protoporphyrin/heme ratio (ZnPP/H) as an indicator of fetal iron status, because unfavorable neurodevelopmental outcomes have been associated with poor iron status at birth, as indicated by low serum ferritin, and because few reliable indicators of fetal and early neonatal iron status exist. Consecutively studied preterm and term fetuses at delivery included the following groups: (1) control nonhypoxic, (2) fetuses with intrauterine growth retardation (IUGR), and (3) fetuses of insulin-treated mothers (FDM). We hypothesized (1) that rapid growth velocity associated with an accelerated erythropoiesis among normal fetuses will lead to reduced iron delivery to a rapidly expanding RBC mass and higher umbilical cord blood RBC ZnPP/H and (2) that fetuses that are exposed to pathologic hypoxemia will experience an additional increase in erythropoiesis and higher cord ZnPP/H. ZnPP/H was determined on saline-washed cord blood erythrocytes by hematofluorometry and was examined for its relationship with clinical factors and cord blood laboratory measurements indicative of tissue oxygenation (plasma erythropoietin [EPO] and reticulocyte count) and iron status (plasma ferritin and erythrocyte indices). Statistical testing included 1-way analysis of variance, 2-way analysis of variance with covariates, simple linear regression, and multiple regression analysis. Among control group subjects, gestational age at birth was inversely correlated with RBC ZnPP/H and reticulocyte count and positively correlated with ferritin and EPO. Relative to control subjects, IUGR and FDM fetuses at specified gestational age groupings had higher ZnPP/H, lower plasma ferritin, and higher plasma EPO. Statistical modeling of the relationship between ZnPP/H and plasma ferritin among all study groups demonstrated significant impacts of gestational age, plasma EPO, maternal hypertension, and maternal smoking. The inverse association of fetal ZnPP/H with gestational age at birth among control subjects is attributable to erythropoietic stimulation likely as a result of increasing growth velocity at the earliest gestational ages. The relatively higher ZnPP/H observed among fetuses in the IUGR and FDM groups likely is attributable to increased erythropoietic activity secondary to pathologic hypoxemia. Decreased placental iron transfer may also have limited iron availability and contributed to elevated ZnPP/H in the IUGR group. These data support the concept that increased erythropoietic activity and/or limited iron transport may place infants of diabetic mothers and infants with growth retardation at risk for developing systemic iron deficiency later in infancy and in early childhood.

Expression of Hepatocyte Growth Factor/Scatter Factor Receptor in IUGR Fetuses’ Placentas: An Immunohistochemical Analysis

Objective: We aimed to evaluate the expression sta tus of c-met, receptor for the hepatocyte growth factor (HGF), in the placentas of intrauterine growth retardation (IUGR) fetuses. Materials and Methods: Placentas were obtained during delivery from both third trimester normal and IUGR complicated pregnancies. Ultrasonographic estimation of fetal birth weight has been done and placentas of those under the fifth percentile for their gestational ages were enrolled in the study group. Eighteen fetuses with IUGR and 6 uncomplicated pregnancies were subjected to the study. Histological sections from placentas were immunohistochemically evaluated for the expression status of c-met. Results: Seventeen of the eighteen patients (94.4%) in the study group were found to have overexpression of the c-met while this figure was only 16.7% (1/6) in the control group (p < 0.0001). There was a strong statistically significant difference between the two groups regarding degree of c-met expression. Conclusion: Our present findings suggest that c-met is an important cell membrane receptor in human placenta. Deregulation of the interaction between HGF and its receptor c-met during placentation may be the cause responsible for the growth retardation of the fetus due to the impaired placental functions.

Prenatal Hypoxia and Cardiac Programming

Epidemiologic studies have shown a clear association of adverse intrauterine environment and an increased risk of hypertension and coronary heart disease in the adult. Many studies have been focused on the effects of maternal undernutrition and fetal glucocorticoid exposure on fetal programming and later adult disease. Although it is relatively less clear, there is evidence that fetal exposure to hypoxia, alcohol, tobacco smoking, and cocaine may also cause in utero programming leading to an increased risk of adult disease. Chronic hypoxia during the course of pregnancy is thought to result in fetal intrauterine growth retardation. Among other effects, chronic hypoxia suppresses fetal cardiac function, alters cardiac gene expression, increases myocyte apoptosis, and results in a premature exit of the cell cycle of cardiomyocytes and myocyte hypertrophy. This review discusses recent evidence of an association of prenatal hypoxic exposure with an increased vulnerability of adult heart disease, and the possible mechanisms involved.

Nonresponsiveness of cerebral p53-MDM2 functional circuit in newborn rat pups rendered IUGR via uteroplacental insufficiency

Severe uteroplacental insufficiency causes cerebral apoptosis in the fetus. Moderate uteroplacental insufficiency causes intrauterine growth retardation (IUGR) and increases the risk of postnatal neurological morbidity. In the rat, uteroplacental insufficiency and IUGR affect cerebral gene expression of Bcl-2 and predispose the newborn IUGR rat toward cerebral apoptosis when challenged with perinatal hypoxia. Expression of Bcl-2, as well as the proapoptotic protein Bax, is regulated by p53. p53 also induces MDM2 transcription, which functions to limit further p53-induced apoptosis. The predisposition of the IUGR fetus toward cerebral apoptosis suggests that the p53-MDM2 "functional" circuit may be perturbed in the newborn IUGR rat brain. We hypothesized that MDM2 cerebral expression does not increase in response to increased p53 expression or increased levels of phospho-p53 (Ser15), an activated form of p53. To prove this hypothesis, we induced IUGR through bilateral uterine ligation of the pregnant rat. Uteroplacental insufficiency significantly increased p53 mRNA, total p53 protein, and phospho-p53 (Ser15) protein levels in the brain at term. Increased expression of phospho-p53 (Ser15) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells were localized to the CA1 region of the hippocampus, the subcortical and periventricular white matter, and the amygdala of the IUGR rat brain. In contrast, uteroplacental insufficiency decreased cerebral MDM2 mRNA and phospho-MDM2 (Ser166) protein levels in the IUGR rat pups. We conclude that the cerebral MDM2 response to increased p53 expression is not present in the newborn IUGR rat pup, and we speculate that this contributes to the predisposition of the IUGR fetus toward perinatal and long-term neurodevelopmental morbidities.

Symmetrical fetal growth retardation after gestational cocaine exposure in the rat

Cocaine use during pregnancy results in an increase in different maternal and perinatal complications. The fetal effects of cocaine could be mainly related to the disturbances in the brain development, microcephaly being the most common brain abnormality. The aim of this study was to analyze maternal outcome and fetal somatic effects of cocaine and to evaluate the hypothesis that maternal cocaine exposure would specifically impair fetal global brain development. Fifty-four timed-pregnant female Sprague–Dawley rats were daily injected with 15 or 40 mg/kg per day from gestational day (GD) 1 or 8 and sacrificed at gestational day 20. By analyzing different maternal and fetal outcomes, it could be suggested that the cocaine exposure in pregnant rats decreased maternal weight gain without significant maternal mortality, did not affect the mean number of fetuses by litter, although notably increased stillbirths, reduced fetal birth weight, and reduced the fetal central nervous system weight. Present results are globally in agreement with the literature and underline a possible selective effect of cocaine on the fetal CNS resulting in symmetrical intrauterine fetal growth retardation in contrast to the asymmetrical retardation of undernutrition.

Effect of esophageal ligation (EL) on small intestinal (SI) development in a rabbit model of intrauterine growth retardation (IUGR)

Cellini, Christina MD; Xu, Jian MD; Buchmiller-Crair, Terry L. MD, FACS Author Information

ANTIESTROGENIC EFFECTS OF ENVIRONMENTAL POLLUTION IN HUMAN BLOOD AND PLACENTA

ISEE-275 Abstract: Modulation of estrogenic activities in humans were investigated in two epidemiological studies in the Central European region. In the first study, total estrogen receptor-mediated activities of extracts from 150 male sera were determined in the breast cancer T47D.Luc cell line stably transfected with a luciferase reporter gene (ER-CALUX assay). Samples from region of Michalovce (Slovakia), heavily polluted with polychlorinated biphenyls, showed generally lower ER-mediated activity, however the decrease in estrogenic activity was not significant. 17beta-Estradiol elicited a major part of the total ER-mediated activity detected in the samples. A specific contribution of persistent organic pollutants to overall estrogenic response was measured in H2SO4/silica fractionated serum extracts. A portion of samples was inactive in the ER-CALUX assay; however, a number of samples eliciting at least a partial estrogenic activity was significantly lower in the PCB-polluted area as compared to the background control region. Moreover, a threefold increase in number of samples showing antiestrogenicity was found in the PCB-polluted area. In summary, this study suggested that antiestrogenic effects and/or suppression of estrogenicity might be associated with long-term PCB pollution. In the second study, human placental aromatase (CYP19) and 7 ethoxyresorufin O deethylase (CYP1A) activities were investigated in 120 human placental samples collected in two Czech Republic urban regions with a different extent of pollution. A significant suppression of the aromatase activity was found in the placental samples from the industrially-polluted district of Teplice (Czech Republic), where airborne pollution is clearly the prevalent way of exposure. Association with the intrauterine growth retardation of fetus was found as well. The CYP1A activity (which is a biomarker of exposure to dioxin-like compounds leading to additional antiestrogenic effect) was elevated only marginally. The human placental aromatase activity in vivo appears to be a prospective biomarker of endocrine disruption pathway which is independent of estrogen receptor.

Obstetrics, Gynaecology and Women's Health

In keeping with their remit to cover women's health in general, O'Connor and Kovacs begin by discussing lifestyle and mental health. Common health issues are then dealt with in order of occurrence, beginning with puberty and proceeding to late life; naturally the chapters on the reproductive years include a large obstetric element. The book is illustrated by clear boxes and flow charts complementing each other: for instance, what investigations to use in cases of fetal intrauterine growth retardation, and how to manage this clinical finding (although here, unusually, the titles do not clearly separate investigations from management). Drawings are numerous and illustrate fetal growth and normal deliveries as well as the different kinds of placental abnormalities. The emphasis in all chapters is on treatment of women as partners and collaborators when choices are to be made (e.g. on contraception or hormone replacement therapy) and on communication. This approach is welcome, and is especially suited to those who attend to women's needs in prevention as well as in disease. These include general or specialist gynaecological nurses, who need a broad knowledge of all different aspects of women's health. Medical students will find here the facts they are expected to know about puberty, pregnancy, and the problems of later years. Some may judge the material on behaviour and psychological problems too unfocused for their purposes or be disconcerted by the chapter on ageing and its concerns, with its wide coverage of ailments of the aged in general. They will be wise to return to these chapters, however, when they study general medicine; they will thus come to see how women's health is much broader than just obstetrics and gynaecology.

Effect of epidermal growth factor infusion on fetal rabbit intrauterine growth retardation and small intestinal development

Background/purpose Intrauterine growth retardation (IUGR) infants have impaired gastrointestinal function with resultant feeding difficulties and predisposition to necrotizing enterocolitis. Supplemented amniotic fluid swallowed by the developing fetus is a potential prenatal treatment for IUGR. Rabbits have naturally occurring IUGR fetuses based on uterine position. To determine intestinal response to epidermal growth factor (EGF) infusion, this rabbit model of IUGR was studied. Methods Eight pregnant rabbits underwent placement of intraamniotic catheters into 2 normal and 2 IUGR fetuses per mother on gestational day 24 of a 31-day gestation. Miniosmotic pumps infused either EGF (about 300 μg/kg/d) or control solution forming 4 study groups (EGF-Favored [Fav] v. Cont-Fav; EGF-IUGR v. Cont-IUGR). On gestational day 31, the fetal gastrointestinal tracts were harvested for analysis. Intestinal epithelial cell proliferation was studied by 5-bromo-2-deoxyuridine (BrdU) incorporation, villus heights were measured, and EGF mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was performed using Students’ t test. Results Fetal survival rate was 87%. EGF-IUGR fetal weights were increased compared with Cont-IUGR fetuses. EGF infusion significantly increased IUGR fetal small intestinal villus height and BrdU-positive small intestinal (SI) crypt cells, all approaching Cont-Fav levels. EGF mRNA was expressed throughout the gastrointestinal tract. Conclusions Supplemental amniotic EGF normalizes fetal weight and intestinal proliferation in the IUGR fetal rabbit. The inclusion of EGF in supplemental amniotic feeding solutions is supported.

Effects of alpha-lipoic acid supplementation on maternal diabetes-induced growth retardation and congenital anomalies in rat fetuses.

The mechanism of diabetic embryopathy is not known. Excessive reactive oxygen species (ROS) produced in diabetes may be causally related to foetal anomalies. The objective of this study was to determine whether supplementation with the antioxidant lipoic acid (LA) could prevent maternal diabetes-related foetal malformations and intrauterine growth retardation (IUGR) in rats. Pregnant rats were non-treated (Group I) or made diabetic on gestation day (GD) 2 by injecting streptozotocin (Group II). Group III was injected with 20 mg kg(-1) of LA daily starting on GD 6 and continued through GD 19. Group IV was administered only Tris buffer on the corresponding days. Group V was a set of STZ-treated animals, which were supplemented with a daily dose of 20 mg kg(-1) of LA from GD 6 through GD 19. All fetuses were collected on GD 20. Lipoic acid did not affect the blood sugar levels of diabetic animals significantly but improved their body weight gain and reduced food and water consumption. Diabetic group had a high incidence of embryonic resorption, IUGR, craniofacial malformations, supernumerary ribs and skeletal hypoplasia. Lipoic acid significantly reduced these abnormalities. These data support the hypothesis that ROS are causally related to fetal maldevelopment and IUGR associated with maternal diabetes in the rat. They also highlight the possible role of antioxidants in the normal processes of embryo survival, growth and development.

Contractile Cardiac Activity in Fetuses with Intrauterine Growth Retardation: Correlations between Regional Nonuniformity, Relaxation, and Afterload

Fetuses of 24 women with normal pregnancies and 14 women with fetal intrauterine growth retardation (IUGR) were tested for shape and movement of the inner borders of the left ventricle (LV) by means of echocardiography. The LV contour was divided into 12 segments. The coefficient of variation (CV) of the movements of individual wall segments was calculated to assess regional nonuniformity of contractions of the LV wall. The ratio between the long and short LV axes was lower in the IUGR group (1.12 ± 0.12) than in the control group (1.75 ± 0.16). Nonuniformity of contractions was higher in the IUGR group (CV = 37.8 ± 17.6%) than in the control group (CV = 21.1 ± 9.9%, P < 0.01). The ratio of the early wave to the atrial wave of transmitral flow (E/A ratio) was lower in the IUGR group (0.69 ± 0.08) than in the control group (0.80 ± 0.08). A negative correlation between the CV and the global ejection fraction of the LV was observed in the fetuses of both groups. In addition, a negative correlation was demonstrated for the E/A ratio and the systolic-to-diastolic flow ratio (S/D ratio) in the umbilical artery. Changes in the shape, nonuniformity of contractions, and diastolic function of the heart in IUGR fetuses are considered to be an adaptation to increased afterload as a result of an elevated resistance of placental vessels.

Circadian Rhythms in Infants

After completing this article, readers should be able to: 1. Describe how circadian rhythms are generated. 2. Describe how lighting influences the circadian system. 3. Delineate the period during which the origin of circadian rhythms develops. 4. Describe the relationship between maternal circadian rhythms and the development of circadian rhythms in infants. 5. Characterize the potential sequelae of impaired fetal and early neonatal circadian rhythms related to sleep patterns. 6. Describe beneficial lighting patterns for preterm infants in the neonatal intensive care nursery. Circadian rhythms are endogenously generated rhythms that have a period length of about 24 hours. Evidence gathered over the past decade indicates that the circadian timing system develops prenatally, with the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, the site of a circadian clock, present by mid-gestation in primates. Recent evidence also shows that the circadian system of primate infants is responsive to light at very early stages (as early as 25 to 28 weeks’ gestation in humans) and that low-intensity lighting can regulate the developing clock. After birth, circadian system outputs mature progressively, with rhythms in sleep-wake cycles, body temperature, and hormone production generally developing between 1 and 3 months of age. The importance of light in regulation of circadian rhythm in infants is highlighted by the early establishment of rest-activity patterns that are in phase with the 24-hour light-dark cycle in preterm infants exposed to low-intensity cycled lighting. With the continued elucidation of circadian system development and influences on human physiology and illness, it is anticipated that consideration of circadian biology will become an increasingly important component of neonatal care. ### The Circadian Timing System Notable examples of circadian rhythms include the sleep-wake cycle and daily rhythms in body temperature and hormone production. Circadian rhythms are also involved in the pathogenesis of illnesses, such as reactive airway disease (eg, asthma) and myocardial infarction. The system responsible …