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Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis and uteroplacental blood flow appears to be an early defect in both the hyperthermic and adolescent paradigms. The effects of these alterations in placental functional development appear to be irreversible. IUGR fetuses are both hypoxic and hypoglycaemic, and have reduced insulin and insulin-like growth factor-1 (IGF-1), and elevated concentrations of lactate. However, fetal utilization of oxygen and glucose, on a weight basis, remain constant compared with control pregnancies. Maintained utilization of these substrates, in a substrate-deficient environment, suggests increased sensitivities to metabolic signals, which may play a role in the development of metabolic diseases in later adult life.

The present knowledge of coronary arteries in prenatal diagnosis is reviewed with a focus on three aspects: the physiology and visualization of coronary flow, malformations involving the coronary arteries, and the "heart-sparing effect". Visualization of coronary arteries in a healthy human fetus is possible in real-time and colour Doppler during the last 10 wk of gestation when ultrasound conditions are excellent. Visualization at an earlier gestational age (up to 13 wk) is feasible mainly in association with malformations and impending hypoxia. The main coronary malformations that can be visualized in utero are the ventriculo-coronary communications in fetuses with pulmonary atresia. In the last few years, interest has been focused on the "heart-sparing effect", defined as the increased perfusion of the coronary arteries in fetuses with severe growth restriction and abnormal Doppler velocimetry in the peripheral vessels. Increased perfusion detectable with colour and pulsed Doppler is a late sign of fetal compromise in hypoxaemia. It confirms animal experiments that have demonstrated dilatory reserves of the fetal coronary arteries under chronic hypoxaemia. The outcome of 21 fetuses showing the "heart-sparing effect" before 32 wk gestation was poor: nine fetuses died in utero and two after birth, the median weight at birth was 630 g. In summary, our knowledge of the coronary arteries in the fetus is based on the diagnostic means used in prenatal diagnosis. New information in this field may also contribute to a better understanding of coronary heart disease later in life.

A new methodology for online detection of intrauterine growth restriction (IUGR) is proposed where traditional methods for statistical surveillance are applied. Here, deficient growth rate is used to detect IUGR instead of the common surrogate measure "small for gestational age" (SGA). Fetal growth is estimated by repeated measurements of symphysis-fundus (SF) height. At each time point the new method, based on the Shiryaev-Roberts method, is used to evaluate the growth in SF height. We use Swedish data to model a normal growth pattern, which is used to evaluate the capability of the new method to detect IUGR in comparison with a method used in practice today. Results from simulations indicate that the new method performs considerably better than the method used today. We also illustrate the effect of some important factors which influence the detection ability and illuminate the tendency of the method used today to misclassify SGA cases as IUGR.

Objective: The fetal cerebral venous circulation during acute hypoxic stress provoked by uterine contractions has not been studied previously. The aim of this study was to explore the cerebral venous circulation during an oxytocin challenge test (OCT) in intrauterine growth-restricted (IUGR) fetuses., Methods: Doppler recordings of blood flow in the vein of Galen (GV), straight sinus (SS) and transverse sinus (TS) before and during uterine contractions and relaxation were obtained at the same time as electronic fetal heart rate (FHR) monitoring in 44 term IUGR fetuses. The OCT was classified as negative (normal FHR) or positive (late FHR decelerations). Non-parametric statistics were used to test differences between OCT groups., Results: In OCT-negative cases (n = 39), de novo pulsations occurred in the GV, and SS flow velocities increased during contractions compared with basal measurements. There were no significant differences in TS flow. Flow recordings were less often obtained from OCT-positive cases (n = 5), making comparisons with OCT-negative cases uncertain., Conclusions: In uncompromised IUGR fetuses an acute cerebral venous hyperperfusion develops in response to uterine contractions. Pulsations in the GV are detected but are unlikely to be an ominous sign in this situation. The more centrally located TS was less discriminating for acute cerebral venous blood flow changes.

Hypoxia and nutrient restriction during gestation restrict fetal growth and alter lung development. As elastin is intimately involved in lung development, our aim was to assess pulmonary elastin synthesis and deposition following intrauterine growth restriction (IUGR) induced by umbilicoplacental embolization (UPE). Pulmonary tropoelastin expression and elastin content were examined at 128 days (5 days UPE) and 140 days (20 days UPE) of the 147- days gestation and at 8 weeks and 2.3 years after birth (both approximately 27 days UPE) in sheep. UPE induced hypoxemia, hypoglycemia, and fetal growth restriction but did not affect pulmonary tropoelastin mRNA levels or elastin deposition at any age; furthermore, elastin content was unaltered apart from being lower at 140 days. The authors conclude that hypoxemia and undernutrition associated with IUGR do not affect elastin synthesis and deposition in fetal lungs; alterations in lung structure following IUGR must have other causes.

Objectives: The purpose was to compare the development of gyrus and sulcus formation (GSF), an indicator of brain maturation, in small-for-gestational-age (SGA) fetuses using magnetic resonance (MR) imaging, with those of appropriate-for-gestational-age (AGA) fetuses., Methods: The 160 infants with a normal neurological outcome were divided into two groups on the basis of their body weight at delivery; 37 SGA infants (Group SGA) and 123 AGA infants (Group AGA). Fetal MR images, which were obtained from 28 to 39 gestational weeks in Group SGA and from 18 to 39 gestational weeks in Group AGA, were classified into the 8 stages of development for GSF established by Abe et al. (2003), and comparison was made between the two groups retrospectively in their neurological development in relation to gestational age., Results: In Group SGA, images were classified into stages 3 to 8 (P < 0.001). The gestational age of the cases determined for each stage between Groups SGA and AGA did not differ significantly, with respect to the development of GSF, despite differences in fetal estimated body weights., Conclusion: In SGA fetuses, evaluation of fetal GSF using MR images during the third trimester may be useful for predicting neurological prognoses postpartum., (Copyright 2004 John Wiley & Sons, Ltd.)

Objective: To examine foetal lung blood perfusion using power Doppler ultrasound (PDU) and to compare fractional moving blood volume (FMBV) and mean pixel intensity (MPI) estimations in the lungs of normally grown (NG) foetuses and foetuses with intrauterine growth restriction (IUGR) and also to correlate foetal lung FMBV and MPI with respiratory complications after birth., Methods: Lungs of 47 NG and 25 IUGR foetuses after 32 weeks of gestation were examined with PDU. FMBV and MPI were estimated in a defined region in the posterior part of the foetal lung closest to maternal abdominal wall. FMBV and MPI were correlated to foetal weight deviation and gestational age. Perinatal outcome and respiratory complications after birth were recorded in both groups., Results: There were significantly lower FMBV and MPI values in IUGR than in NG foetuses. The overall variation was lower for FMBV than for MPI. There was a slightly higher correlation between FMBV and foetal weight deviation [r = 0.33, 95% confidence intervals (CI) 0.11-0.52] than between MPI and foetal weight deviation (r = 0.26, 95% CI 0.03-0.46). There was no significant correlation between FMBV or MPI and gestational age. No differences between the groups were found in the rate of respiratory complications, and they were not correlated either to the FMBV or MPI., Conclusion: FMBV and MPI, estimated from the PDU signals of foetal lung circulation, showed lower values in third-trimester pregnancies complicated by IUGR. The frequency of neonatal respiratory complications was not increased in cases with low pulmonary FMBV and MPI values.

Background: The aim of this study was to investigate the occurrence and appearance of the anastomosis between the two umbilical arteries in placentas from infants small for gestational age (SGA)., Methods: The arterial systems of 64 placentas from singleton pregnancies resulting in SGA infants were visualized by angiography. The method allowed study of the anastomosis between the umbilical arteries and calculation of the relative placental area supplied by each artery. The results were compared with findings in a previous study of appropriate for gestational age (AGA) infants. One-way analysis of variance (ANOVA) and chi2-analyses were used for statistics., Results: In 56 placentas the anastomosis was represented by a true vessel, in two by a fenestration, and in another two cases by fusion of the umbilical arteries. The anastomosis was absent in one case and another three cases had a single umbilical artery (SUA). When the diameter of the anastomosis was thinner than that of the umbilical arteries, their supply areas were significantly (p < or = 0.001) more symmetrical than in cases with a wider anastomosis. The anatomy of the anastomosis and the relationship between its width and the symmetry between the supply areas of each umbilical artery did not differ in placentas from SGA and AGA infants, despite various types of cord insertion and placentation., Conclusion: Static measurements of Hyrtl's anastomosis do not indicate a contributing part for intrauterine growth retardation.

Objective: To assess reference ranges for fetal coronary sinus (CS) diameter and to compare them with values from fetuses showing heart defects with and without left superior vena cava (LSVC) as well as with severe intrauterine growth retardation and heart-sparing effect on color Doppler., Methods: The coronary sinus was visualized on two-dimensional ultrasound in a plane slightly caudal to the apical four-chamber view. For the normal range of the size of the CS in relation to gestational age, data was collected from 108/114 (95%) normal fetuses with good visualization between 20 weeks' gestation and term. Abnormal conditions comprised two groups: group 1 consisted of 52 fetuses with heart anomalies, including three subgroups: 11 fetuses with isolated LSVC emptying into the coronary sinus, 12 fetuses with LSVC associated with structural heart defects and 29 fetuses with structural heart defects but without LSVC. Group 2 consisted of 11 fetuses with severe intrauterine growth retardation and dilated coronary arteries as seen by color Doppler ultrasound., Results: Under normal conditions, there was a significant increase in the CS diameter with advancing gestational age (1.2-2.7 mm). Significant dilatation was found only in the two groups with LSVC (range 2.7-6.5 mm), independent of whether the finding was isolated or associated with cardiac defects., Conclusion: CS visualization and measurements are easily feasible in the human fetus in the apical four-chamber view. Significant dilatation of the CS is a sign of LSVC. The examiner should be aware of this condition as such dilatation is commonly falsely diagnosed as atrial or atrioventricular septal defect., (Copyright 2003 John Wiley & Sons, Ltd.)

The outcome of Down syndrome fetuses presenting with sonographic abnormalities in the second or third trimester is unclear. Therefore, we studied 55 pregnancies referred because of sonographically suspected fetal structural anomalies or growth retardation due to trisomy 21. A detailed ultrasound scan was performed in all cases to delineate the structural anomalies. Congenital heart malformations (CHMs) were diagnosed pre- and postnatally in 29 out of 55 Down fetuses (53%), with complete or incomplete atrioventricular septal defects (AVSDs) and ventricular septal defects (VSDs) being the most frequent anomalies. The most frequent noncardiac findings were a short femur (45%) and a small-for-gestational age (SGA) fetus (27%). Termination of pregnancy was carried out in 25 out of 55 pregnancies (45%). Of the 30 continued pregnancies, 10 ended with intrauterine death. The remaining 20 pregnancies resulted in the delivery of a live-born infant whose prognosis was poor, with a 1-year survival of only 60%. Combining intrauterine death and death in the first year indicated that the overall survival rate was only 40%. Fatal outcome was noted in 68% (13/19) in the presence of CHM, in 83% (10/12) in SGA fetuses, in 86% (6/7) in combined CHM and SGA, but only in 17% (1/6) in the absence of CHM and SGA. This study indictes that second- and third-trimester in utero diagnosis of Down syndrome has a poor outcome when associated with CHM and/or SGA. This is important in the genetic counseling of the parents., (Copyright 2002 Wiley-Liss, Inc.)

Intrauterine growth restriction (IUGR) is a significant health issue that not only affects infant mortality and morbidity, but may also predispose individuals to coronary heart disease, diabetes, hypertension and stroke as adults. The majority of IUGR pregnancies in humans are characterized by asymmetric fetal growth, resulting from inadequate nutrient transfer to the fetus. Furthermore, most of these pregnancies involve functional placental insufficiency, and may also show altered umbilical velocimetry. As the severity of IUGR increases, the fetus becomes increasingly hypoxic, hypoglycaemic and acidotic. In addition, placental transfer or utilization of some amino acids is known to be altered in IUGR pregnancies. Although a great deal has been learned from clinical studies of human IUGR, appropriate animal models are required to define completely the mechanisms involved in the development of IUGR. The pregnant sheep is a long-standing model for placental-fetal interactions, and fetal growth restriction can be induced in pregnant sheep by maternal nutrient restriction, maternal nutrient excess, administration of glucocorticoid, utero-placental embolization, carunclectomy and maternal hyperthermia. Although all of these sheep models are capable of inducing fetal growth restriction, the degree of restriction is variable. This review compares these sheep models of IUGR with the characteristics of human IUGR.

Objective: To investigate the efficacy and safety of intrapartum fetal pulse oximetry, as a predictor of metabolic acidosis at birth of fetuses with intrauterine growth retardation (IUGR)., Study Design: We studied 18 IUGR fetuses (group I) and a control group of 30 appropriate for gestational age (AGA) fetuses (group II) during labor. Both groups had abnormal fetal heart rate tracings and were monitored simultaneously throughout labor with cardiotocography and fetal pulse oximetry. Apgar scores, pH and base excess of fetal blood obtained from the umbilical artery after delivery were compared in both groups., Setting: The Fetal Surveillance Unit of the 2nd Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, Athens University., Results: In IUGR fetuses, when their oxygen saturation value (FSPO2) was less than 34%, cord artery pH was 7.10 +/- 0.04, base excess -13 +/- -1 mmol/l and Apgar scores < or =5 at the 5th min, and when FSPO2 was over 35%, artery pH was 7.29 +/- 0.08, base excess -8 +/- -2 mmol/l and Apgar scores > or =7 at the 5th minute. In cases of drops of FSPO2)below 30% for more than 2 min, labor was completed operatively and cord pH was 7.00 +/- 0.04, base excess -15 +/- -2 mmol/l and Apgar scores < or =5 at the 5th minute. In AGA fetuses, when FSPO2 was over 30%, artery pH was over 7.20, base excess <-11 mmol/l and Apgar scores > or =9 at the 5th minute; in contrast, when FSPO2 was <30% for 2 min, a cesarean section was performed and cord pH was < or =7.02, base excess > or =-13 mmol/l and Apgar scores < or =4 at the 5th minute., Conclusions: In IUGR fetuses, FSPO2 values less than 34% represent an acidotic status, while values of > or =35% are well tolerated. Fetal pulse oximetry proved reliable, according to umbilical cord blood measurements and Apgar scores, reducing cesarean deliveries in cases of nonreassuring cardiotocographic patterns in IUGR fetuses., (Copyright 2003 S. Karger AG, Basel)

IGF binding protein-1 (IGFBP-1) is a secretory product of decidualized endometrium and a major constituent of amniotic fluid. It is thought to modulate the actions of the IGFs on trophoblast cells and is therefore potentially important in regulating placental development and fetal growth. To investigate this hypothesis, we have studied the effects of decidual IGFBP-1 excess on fetoplacental growth in transgenic mice overexpressing human IGFBP-1. Endogenous fetal IGFBP-1 overexpression is associated with a transient impairment of fetal growth in midgestation. Maternal decidual IGFBP-1 excess is also associated with impaired fetal growth in midgestation independent of fetal genotype, indicating placental insufficiency. Our data also demonstrate that amniotic fluid IGFBP-1 is derived almost exclusively from maternal sources. Decidual IGFBP-1 overexpression has a marked effect on placental development. Placental morphology is abnormal in transgenic females due to altered trophoblast invasion and differentiation. These changes result in an increase in placental mass throughout pregnancy. This study provides the first compelling in vivo evidence that IGFBP-1 plays a role in placentation and suggests that IGFBP-1 has a pathological role in preeclampsia, a disorder characterized by shallow uterine invasion and altered placental development.

The radiation-induced mutation minute (Mnt) in the mouse leads to intrauterine growth retardation with paternal transmission and has been linked to the distal chromosome 7 cluster of imprinted genes. We show that the mutation is an inversion, whose breakpoint distal to H19 disrupts and thus identifies an enhancer for Igf2 expression in skeletal muscle and tongue, and separates the gene from other mesodermal and extra-embryonic enhancers. Paternal transmission of Mnt leads to drastic downregulation of Igf2 transcripts in all mesodermal tissues and the placenta. Maternal transmission leads to methylation of the H19 differentially methylated region (DMR) and silencing of H19, showing that elements 3' of H19 can modify the maternal imprint. Methylation of the maternal DMR leads to biallelic expression of Igf2 in endodermal tissues and foetal overgrowth, demonstrating that methylation in vivo can open the chromatin boundary upstream of H19. Our work shows that most known enhancers for Igf2 are located 3' of H19 and establishes an important genetic paradigm for the inheritance of complex regulatory mutations in imprinted gene clusters.

Aims/hypothesis: We have shown that perinatal malnutrition decreases beta-cell mass at birth and impairs the adaptation of the endocrine pancreas to a subsequent pregnancy. The aim of this study is to investigate the impact of this maternal inadaptation on the development of endocrine pancreas in foetuses., Methods: Female rats malnourished during their perinatal life and showing intra-uterine growth retardation at birth were mated at 8 months of age. The development of the endocrine pancreas was studied at embryonic days 14, 17 and 20 in their foetuses by immunohistochemistry and morphometrical measurements on pancreatic sections., Results: At embryonic day 20, both alpha and beta-cell fractions were decreased in foetuses from IUGR dams. Beta-cell mass was reduced (197 +/- 27 microg, vs 281 +/- 40 microg in control, p < 0.01) and so were insulin content and islet number per cm(2), as in the first generation foetuses. At embryonic day 14, the number of cells expressing only insulin was decreased by half in foetuses from intra-uterine growth retardation dams. At embryonic day 17, 50 % of the homeodomain protein Pdx-1 cell population expressed insulin but all the insulin cells expressed Pdx-1 in both groups; in foetuses from intra-uterine growth retardation dams the number of epithelial cells expressing Pdx-1 was decreased (415 +/- 40 cells/ mm(2) vs 481 +/- 28 cells/mm(2) in control foetuses, p < 0.05) and the mesenchymal fraction in the pancreas was increased by 36 % ( p < 0.05)., Conclusion/interpretation: Early malnutrition decreases beta-cell mass in the first generation of offspring and impairs the subsequent beta-cell adaptation to pregnancy. The beta-cell alteration is also present in the next generation and involves a decreased expansion of the epithelial population expressing Pdx-1.

Insulin-like growth factor I (IGF-I) is an important regulator of fetal growth, and circulating concentrations are reduced in intrauterine growth-restricted (IUGR) fetuses. We investigated whether IGF-I administered into amniotic fluid could ameliorate IUGR in fetal sheep. Fetuses were assigned to control (n = 9), IUGR+saline (n = 12), or IUGR+IGF-I groups (daily intra-amniotic IGF-I injections of 20 microg, n = 13). IUGR was induced by placental embolization from 114 to 120 days. Treatment was from 120 to 130 days of gestation. Embolization produced asymmetrically IUGR fetuses with decreased body weight and lighter, thinner-walled guts. Fetal plasma and amniotic IGF-I levels were reduced. During treatment, fetal plasma, but not amniotic, IGF-I levels recovered in the saline group but remained depressed in the IGF-I-treated group. IGF-I treatment restored gut weight and wall thickness to control levels and increased the number of crypt mitoses. Fetal weight was similar to that of controls, but spleen, liver, and thymic weights were reduced by 30-37%, and placentome growth was altered. Amniotic fluid IGF-I supplementation may provide the basis of future therapeutic approaches to IUGR, but the systemic effects require further investigation.

Objective: The purposes of our study were to assess the ability of color and power Doppler sonography to depict the blood flow in the intraplacental villous arteries and to evaluate whether the blood flow of intraplacental villous arteries in a normal pregnancy is different from that in a pregnancy that is associated with intrauterine growth restriction., Study Design: Eighty-five women with uncomplicated pregnancy and 16 women with intrauterine growth-restricted fetuses between 27 and 38 weeks of gestation were examined by color and power Doppler imaging. The blood flow of intraplacental villous arteries was analyzed comparatively. The pulsatility index and peak systolic velocity were measured., Results: A unit of 1 intraplacental villous artery-1 and its branches were seen as 1 cotyledon by color and power Doppler imaging. The cotyledon was easily identified and counted. Each cotyledon contained only 1 intraplacental villous artery-1. This method can visualize the intraplacental villous artery-1 to intraplacental villous artery-4 in normal pregnancies. The terminal villous arteries beyond intraplacental villous artery-4 were not imaged. The number of detectable intraplacental villous artery-1 in 1 placenta in intrauterine growth restriction was significantly lower than that in normal pregnancy. The number of detectable branches in intrauterine growth restriction was also significantly lower than in normal pregnancy. No intraplacental villous artery-4 blood flow was found in women with intrauterine growth restriction. In examined arteries, pulsatility index decreased and peak systolic velocity increased significantly with advancing gestational age (P <.02). At any given gestational age, pulsatility index and peak systolic velocity in the peripheral arteries were significantly lower than those in the upstream arteries in normal pregnancy (P <.001). The pulsatility index value of each intraplacental villous artery was also lower than that of the umbilical artery in the women with intrauterine growth restriction (P <.05). There were no differences in pulsatility index in each artery between the groups, although there were a few high pulsatility index values in intrauterine growth restriction., Conclusion: Color Doppler and power flow sonography are valuable tools for the detection of the blood flow of intraplacental villous arteries. The decrease in the number of detectable intraplacental villous artery-1 and branches was associated with intrauterine growth retardation.

Glucose intolerance in adults born with intrauterine growth retardation (IUGR) may involve peripheral insulin resistance and/or abnormal endocrine pancreas development during fetal life. We quantified insulin-containing cells in deceased human fetuses with IUGR (<10th percentile, n = 21) or normal growth (control fetuses, n = 15). Paraffin-embedded pancreatic tissues from fetuses older than 32 weeks were obtained from two fetopathology departments. Mean gestational age was 36 weeks in both groups. Tissues with lysis and those fetuses with defects, aneuploidy, or genetic abnormalities were excluded. For each subject, six pancreatic sections spaced evenly throughout the organ were immunostained with anti-insulin antibody. Total tissue and insulin-positive areas were measured by computer-assisted quantitative morphometry. Results were expressed in percentages. To evaluate islet morphogenesis, the percentages of beta-cells inside and outside islets were determined. Islet density was similar in the two groups (P = 0.86). The percentage of pancreatic area occupied by beta-cells (beta-cell fraction) was not correlated with gestational age (r = 0.06 and P = 0.97 in IUGR fetuses; r = 0.12 and P = 0.67 in control fetuses) or body weight (r = 0.16 and P = 0.47 in IUGR fetuses; r = 0.24 and P = 0.39 in control fetuses). Mean beta-cell fraction was 2.53% in the IUGR fetuses and 2.86% in the control fetuses (P = 0.47). The percentage of beta-cells located within islets was identical in the two groups (mean 35%). Our data militate against a primary developmental pancreatic abnormality in human IUGR, leaving peripheral insulin resistance as the most likely mechanism of glucose intolerance in adults born with IUGR.

There is substantial evidence linking birth size with the risk of developing cardiovascular disease and its major biological risk factors in adulthood. The fetal origins hypothesis proposes that these diseases originate through adaptations, which the fetus makes when it is undernourished. These adaptations may be cardiovascular, metabolic, or endocrine. They permanently change the structure and function of the body. Prevention of the diseases may depend on prevention of imbalances in fetal growth or imbalances between prenatal and postnatal growth, or imbalances in nutrient supply to the fetus. The purpose of this article is to examine some of the more recent epidemiological associations between low birth weight and adult atherosclerotic vascular disease and its risk factors. We will also discuss mechanisms that might explain these associations.

Objective: Current treatment of patients with selective intrauterine growth retardation in monochorionic twins includes expectant management, termination of pregnancy, or umbilical-cord occlusion. The purpose of this study was to assess the outcome of monochorionic twins with selective intrauterine growth retardation who were treated with selective laser photocoagulation of the communicating vessels., Study Design: Monochorionic twin pregnancies with selective intrauterine growth retardation at less than 26 weeks were eligible for the study. Selective intrauterine growth retardation was defined as <10th percentile for gestational age. Absent or reverse end-diastolic velocity in the umbilical artery of the twin with selective intrauterine growth retardation was required for eligibility after January 2000., Results: Thirty patients met the criteria for the study: 17 patients were treated expectantly (group I); 2 patients underwent umbilical-cord ligation of the twin with selective intrauterine growth retardation, and 11 patients underwent selective laser photocoagulation of the communicating vessels (group II). Survival rates for at least 1 fetus were no different between groups I and II (14/17 [82.3%] vs 8/11 [72.3%]; P = .4). However, concomitant demise of the co-twin occurred in 4 of 7 patients, and iatrogenic premature delivery for deterioration of the twin with selective intrauterine growth retardation was necessary in 2 patients in group I, which resulted in significant neonatal morbidity. Of the live-born babies, neurologic handicap was present in 3 of 22 babies (13.6%) versus 0 of 12 in groups I and II, respectively (P < .0001)., Conclusion: Selective intrauterine growth retardation in monochorionic twins can be effectively treated with selective laser photocoagulation of the communicating vessels. By unlinking the circulations between the fetuses, the pregnancy is rendered "functionally" dichorionic, which improves pregnancy treatment and results in decreased neonatal morbidity. This approach constitutes a new valuable alternative in the treatment of monochorionic twin pregnancies with selective intrauterine growth retardation. A randomized clinical trial of expectant treatment versus selective laser photocoagulation of the communicating vessels for monochorionic selective intrauterine growth retardation can be considered.

Abnormal spectra of blood flow are observed in many fetal vessels in pregnancy complicated by intrauterine growth restriction. Redistribution of blood flow to the most important organs causes a diminished perfusion of the others. The disturbances of lung perfusion in utero are related to abnormal growth and development of the fetal lung. The aim of this study was to describe blood flow velocity waveforms in fetal pulmonary veins in normally grown and growth restricted fetuses above 30 weeks of gestation. Doppler studies were performed in 53 normally grown and 39 growth restricted fetuses. The subjects of analysis were: peak systolic (VS), peak diastolic (VD), end-diastolic (VA), and pulsatility index for veins (PIV). Analysis was performed for two gestational intervals: 31-36, 37-41 wks. The pulmonary venous flow in growth retarded fetuses demonstrates the similar pattern to that observed in normally grown fetuses above 30 weeks of gestation. There were no statistically significant differences between normally grown and growth restricted fetuses in all analyzed indices in both gestational intervals.

Antenatal glucocorticoids are thought to be less effective when delivery occurs more than 7 d after initiation of treatment; therefore, repeat courses are often administered. We examined lung structure after single or repetitive antenatal glucocorticoid injections in fetal sheep. Pregnant ewes received single or repetitive doses of 0.5 mg/kg betamethasone at 7-d intervals by maternal or fetal injection, beginning at D104 or D114 with delivery at D125, D135, or D146 gestation (term = 150 d). Changes in lung structure were more pronounced after repetitive versus single injections. Repetitive fetal or maternal injections beginning at D104 (delivery at D125) resulted in comparable structural changes: alveolar volume increased by 50 to 80%, alveolar numerical density decreased by 30 to 40%, and pleural and interlobular septal volumes decreased by as much as 70%. Similar changes were seen in animals delivered at D135 after repetitive maternal injections beginning at D114. There were no structural differences between control and repetitive betamethasone animals when delivery was delayed until D146, indicating that betamethasone induced structural changes were reversible.

Background: Diagnosis and management of intrauterine growth retardation during pregnancy remain a major challenge in obstetric care. The objective of this survey was to evaluate the routine clinical management of pregnancies with suspected intrauterine growth retardation at obstetric departments in Sweden., Methods: In 1997, a questionnaire was sent to all 59 obstetric departments in Sweden. Forty-two departments, caring for 83% of all deliveries in Sweden, replied. Four major topics were addressed: definition and diagnosis of intrauterine growth retardation; magnitude of the problem; clinical management; use of Doppler ultrasound in clinical decision-making., Results: Intrauterine growth retardation is diagnosed by a combination of serial fundal height measurements and ultrasonic fetal biometry at 40 departments, two departments perform routine fetal biometry at 32 weeks. The diagnosis is most often made at 32-36 gestational weeks. Five departments use 1.5 s.d. below the mean as cut-off point for diagnosis of small for gestational age fetuses; 35 departments use mean - 2 s.d. and two departments mean - 2.5 s.d. Intrauterine growth retardation is suspected in 1.6-6.3% pregnancies. About 19% of patients with suspected intrauterine growth retardation are hospitalized. On average, 63% of all small-for-gestational age babies are diagnosed prenatally. Thirty-nine out of 42 obstetric departments use formalized management protocols. All departments use cardiotocography, repeat ultrasound scans and Doppler ultrasound for antenatal surveillance., Conclusions: In Swedish obstetric units, the diagnostic procedures and methods of fetal surveillance in pregnancies suspected of intrauterine growth retardation are more or less uniform. Doppler examination of umbilical artery is used at all responding departments and is considered a valuable asset in clinical decision-making.

In victims of sudden infant death syndrome (SIDS), renal development has been reported to be significantly impaired. In the present study, we used stereological techniques to estimate volume of kidney cortex and total number of glomeruli in a group of human infants. Infants were classified according to cause of death-SIDS or non-SIDS. Cases were further subdivided according to birth weight-normal birth weight (NBW) or low birth weight (LBW) (we were unable to identify any non-SIDS LBW infants for our study). No significant differences were found between NBW and LBW infants (irrespective of cause of death) for cortical volume, glomerular density, or total glomerular number (p > 0.140). Kidney cortical volume, glomerular density, and total glomerular number were not significantly different between SIDS and non-SIDS infants (p > 0.510). Glomerular number was only significantly less in SIDS infants of LBW (p = 0. 032) than in controls according to the Wilcoxon rank sum test; using the Kruskal-Wallis for one-way analysis, no significant difference was found (p > 0.010). These results contrast with those from previous studies, as a reduction in glomerular number was not noted in SIDS NBW infants, and the mean value for the control (non-SIDS NBW) group was significantly reduced (p < 0.01) from those of previous studies. This indicates that glomerular number reduction is seen in SIDS NBW and non-SIDS NBW cases and is therefore directly associated with growth retardation rather than with SIDS.

The effect of intrauterine growth restriction (IUGR) on renal hemodynamics and excretory functions was studied in 76 newborn piglets 12-27 h old. The experiments were performed on anesthetized animals divided into normal-weight piglets and IUGR piglets according to their birth weight. The "normal-weight" category included animals with a birth weight >40th percentile (piglets heavier than 1,220 g); the IUGR category included animals with a birth weight >5th and <10th percentiles (piglets with a birth weight between 733 g and 853 g). Cardiac output and renal blood flow were measured by the colored microsphere technique. Urine was collected from catheters placed in the ureters. This animal model of naturally occurring growth retardation in swine gives asymmetric growth with an increase in the mean ratio of brain weight to liver weight from 1.02 to 1.85 (P<0.01). Thus there was only a small reduction in brain weight (11%). In contrast, the reduction in the weight of liver (50%) and kidney (46%) was proportional to that in body weight (46%). Heart rate, cardiac output, arterial blood gases, and pH were similar in normal-weight and IUGR piglets, but arterial blood pressure and arterial glucose content were significantly reduced in IUGR piglets (P<0.01). Moreover, IUGR piglets had higher plasma catecholamine levels (P<0.05). Renal blood flow and renal vascular resistance were similar in the normal-weight and in the IUGR groups. However, in IUGR animals, glomerular filtration rate was significantly less than in the controls (P<0.05). Normal-weight and IUGR newborn piglets reabsorbed sodium very efficiently, the fractional sodium excretion was less than 1% in both groups. We conclude that renal blood flow is maintained in relation to kidney and body weight in IUGR newborns, but that important renal excretory functions are compromised due to IUGR.

In 9 pregnancies complicated by intrauterine growth restriction, 24-hour fetal heart rate recordings were made before and after betamethasone treatment to study the influence of cortisol on diurnal fetal heart rate rhythms. Maternal and fetal rhythms were correlated and did not change after betamethasone administration. We conclude that diurnal fetal heart rate rhythms are synchronized by the mother through a mechanism other than adrenal control.

Many cases of intrauterine growth retardation (IUGR) result from placental insufficiency, but the molecular signals accompanying this event are unknown. Insulin-like growth factor 1 (IGF-1) is a potent mitogen for fetal tissues and is lowered in the serum of human infants with IUGR. The rabbit provides an optimal model for the study of IUGR based on fetal position. To determine if IGF-1 expression is altered in the growth-retarded fetus, this naturally occurring rabbit model of IUGR was used. Four fetal rabbit pairs were harvested on Days 21, 23, 25, 27, 29, and 31 of their normal 31-day gestation; they were identified based on uterine position as normal or growth retarded. Fetal weight was recorded and the serum, amniotic fluid, liver, kidney, and small intestine (SI) were collected. The SI was divided into three equal segments: proximal, middle, and distal. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure IGF-1/beta-actin mRNA densitometric band ratios in all tissues. Radioimmunoassay (RIA) was used to measure IGF-1 protein levels in the serum and amniotic fluid. Statistical analysis was performed using ANOVA and the paired Student's t test. Weights were decreased in fetuses with IUGR at all time points (P < 0.05), further validating this rabbit model in the study of IUGR. Liver, proximal, and distal SI IGF-1 mRNA decreased during late gestation (P < 0.01). Kidney IGF-1 mRNA increased throughout late gestation (P < 0.01). Compared with their normal counterparts, fetuses with IUGR had a trend toward decreased IGF-1 mRNA in the kidney, liver, and SI at all time points, reaching significance in the liver on Day 27 (P = 0.002). Serum IGF-1 decreased throughout gestation in all fetuses (P < 0.05). Compared with normal fetuses, fetuses with IUGR had lower serum IGF-1 at all time points, reaching significance at Day 27 (P = 0.02). Amniotic fluid IGF-1 was lower in fetuses with IUGR than in normal fetuses, though not quite reaching significance. Compared with normal fetuses, growth-retarded fetal rabbits trend toward depressed liver, kidney, and intestinal expression of IGF-1 mRNA and lower serum and amniotic fluid IGF-1 protein. Serum IGF-1 levels correlate with fetal weight change. Further studies and potential manipulation of fetal IGF-1 are warranted to investigate potential prenatal intervention in the treatment of IUGR., (Copyright 2000 Academic Press.)

The object of this study was to investigate the fetal renal arterial blood flow in normal and hyperechogenic kidneys during the third trimester of gestation. The pregnancies screened were all chronically hypoxic. Depending on the etiology of the intrauterine chronic hypoxia, the cases were divided into two study groups. Group I comprised 120 pregnant women with pregnancy-associated hypertension and/or proteinuria. Group II consisted of 87 pregnancies with intrauterine growth retardation. Both study groups included pregnant women from the third trimester. Hyperechogenic renal medullae were detected in 15 out of 120 cases with pregnancy-associated hypertension and/or proteinuria, and in 22 fetuses of the 87 pregnancies involving intrauterine growth retardation. Fetal renal hyperechogenicity appears to be an indicator of fetal arterial circulatory depression, correlated with pathological changes in the resistance index for the fetal renal arteries. The fetal renal arterial blood flow resistance index was significantly lower in hyperechogenic cases. This may also be an in utero indication of subsequent intrauterine and neonatal complications, such as cesarean section because of fetal distress (43%), treatment in a neonatal intensive care unit (51%) or increased perinatal mortality (5.4%, as compared with 0.8-1.0% in the normal population). Detailed ultrasound and Doppler examinations of renal parenchyma and arteries appear to be useful methods in the prenatal diagnosis of reduced renal perfusion and of intrauterine hypoxia to detect possible pathological fetal conditions in utero.

It has been shown that IGF-I has an anabolic effect in the normal fetus. However, there is evidence to suggest that there may be IGF-I resistance in the growth retarded fetus. Therefore, we investigated the effects of acute IGF-I infusion to chronically catheterised fetal sheep. At 128 days gestation, fetuses underwent a 4 h infusion of IGF-I (50 microg/kg/h). Three groups of animals were studied. Nine normally grown fetuses were studied as controls. Embolised animals (n=8) received microspheres into the uterine vasculature, and animals with spontaneous intra-uterine growth retardation (IUGR animals) (n=6) were fetuses found at post mortem to be spontaneously growth restricted. The effects of IGF-I infusion on feto-placental carbohydrate and protein metabolism were similar in our control group to previous similar experiments. IGF-I infusion decreased fetal blood glucose, oxygen, urea and amino-nitrogen concentrations, and inhibited placental lactate production. The same fetal blood metabolite concentrations also fell during IGF-I infusion in the embolised fetuses, but the effect on placental lactate production was not seen. The only effect of IGF-I infusion in the spontaneous IUGR animals was a fall in fetal blood amino-nitrogen concentrations. We conclude that fetal IGF-I infusion does not have the same anabolic effects in the growth retarded fetus as the normal fetus. In addition, the effects of IGF-I were different in the two growth retarded groups. Our data support previous evidence that the growth retarded fetus has altered IGF-I sensitivity, and this may vary depending on the cause, severity and duration of growth retardation.

Background: Intrauterine growth restriction (IUGR) has been linked to impaired renal function and hypertension, suggesting that an adverse prenatal environment could alter kidney development and renin production., Methods: Immunohistochemistry and in situ hybridization were employed to localize renin-containing cells (RCCs) in the deep, middle, and superficial zones of autopsy kidney sections, in parallel with histologic maturation, from unexplained stillborn fetuses of normal weight (N = 26) and stillborn fetuses with IUGR (N = 17)., Results: In the control group, the number of RCC per 100 glomeruli in the deep zone decreased with advancing gestation from 40 at 20 weeks gestation to five at term (P < 0.001), whereas the opposite change was found in the superficial zone (increase from 5 per 100 to 55 per 100; P < 0.001). In the IUGR group, the density of RCCs in both the superficial and deep zones was similar to the control group at 20 weeks, and no shift in renin gene expression was observed as gestation advanced. Histologic maturation was unaltered., Conclusions: Renin gene expression persists and predominates in the deep renal cortex of the stillborn IUGR fetus, and could contribute to the pathogenesis of neonatal oliguria and/or hypertension during postnatal life.

In utero diagnosis of fetal growth abnormalities continues to pose a clinical dilemma. Although significant advances have been made in the understanding of growth disturbances and their clinical importance, false-positive and false-negative diagnoses of IUGR and excessive fetal growth continue to affect the accuracy of antenatal diagnosis. Until more accurate methods are developed to aid in diagnosis, multiple biometric parameters should be assessed in patients either at risk for or with a suspected growth disturbance. Serial measurements obtained every 2 to 3 weeks may enhance diagnostic capabilities. Although antenatal diagnosis of IUGR has been shown to be of benefit in improving outcome, more study is needed to determine whether there is a benefit in antenatal diagnosis of macrosomia or LGA.

A competent permeability barrier must be present by the end of gestation to allow for life in a terrestrial environment. Indeed, early preterm infants display serious complications of skin immaturity. Yet, regardless of their degree of prematurity, all infants quickly develop a competent barrier. To learn more about the mechanisms and regulation of barrier ontogeny, we have utilized late-gestation fetal rodents. In 19-21 d fetal rats, we showed that barrier competence is accompanied by both enhanced epidermal development and formation of extracellular lamellar membranes in the stratum corneum. The identical sequence and time-course occurs when fetal rat skin is cultured in a serum-free medium. Glucocorticoids, thyroid hormone (T3), and estrogen accelerate, while androgens delay barrier formation both in utero and in the in vitro system, explaining the poorer outcome of premature males versus females. But neither T3 nor glucocorticoids are absolutely required for barrier development. Lifting fetal skin cultures to an air-medium interface also accelerates barrier formation, explaining the rapid emergence of barrier competence in very premature infants. PPARalpha and FXR activators, which, like T3, heterodimerize with the nuclear receptor, RXR, also accelerate barrier development in vitro. Finally, not only the nuclear receptor family, but also Ca++ could regulate key events late in barrier development.

Uteroplacental insufficiency alters the anabolic metabolism of the fetus, resulting in intrauterine growth retardation (IUGR). The metabolic and physiologic factors that cause IUGR have long standing consequences after birth. Postnatal growth and glucose metabolism are altered in the IUGR infant. Skeletal muscle is an important component of growth and metabolizes up to 70% of i.v. glucose. The ability of skeletal muscle to metabolize glucose is affected by ATP availability. We hypothesized that gene expression and function of proteins involved in mitochondrial ATP production and distribution would be altered in juvenile IUGR muscle. To test this hypothesis, we used a model of IUGR, induced by bilateral uterine artery ligation in the pregnant rat, that mimics uteroplacental insufficiency in the human. RT-PCR was used to measure the mRNA levels of three important mitochondrial proteins; NADH-ubiquinone-oxireductase subunit 4L(ND-4L), subunit C of the F1F0-ATP synthase (SUC), and adenine nucleotide translocator 1 (ANT1) in IUGR and control rats in fetal and juvenile life. In the fetus, mRNA levels of all three proteins were significantly increased in IUGR skeletal muscle. In contrast, in juvenile animals, mRNA levels of all three proteins were significantly decreased. mRNA levels of other metabolically important proteins, glucose-6-phosphate dehydrogenase and carnitine-palmitoyl-transferase II, were not significantly altered in IUGR juvenile animals. To assess if decreased gene expression is associated with altered mitochondrial function, we measured the mitochondrial NAD+/NADH ratio in d 21 juvenile control and IUGR muscle. At d 21, decreased gene expression if ND-4L, SUC, and ANTI is associated with a decreased mitochondrial NAD+/NADH ratio. The results of our study suggest that the metabolic alterations associated with uteroplacental insufficiency in the rat result in altered fetal and postnatal muscle mitochondrial mRNA expression as well as altered postnatal mitochondrial function.

The Cavalieri method has been applied in combination with gradient echo magnetic resonance imaging (MRI) to investigate the increase in the volume of the fetus and fetal brain in the third trimester of pregnancy. Eighteen women with singleton pregnancies were recruited. Birthweights for the fetuses all lay within the 10-90th centile based on Liverpool data. A regression analysis, weighted using values derived from the coefficient of error predicted for each volume estimate, revealed a linear relationship between total fetal volume and gestational age (R2 = 0.88) and between fetal brain volume and gestational age (R2 = 0.71) during the third trimester. Fetal volume increased by an average of 25.2 ml per day and fetal brain volume increased by an average of 2.3 mL per day. Fetal brain volume is on average a constant proportion (10%, SD = 2%) of total fetal volume throughout the third trimester. Volume data were also obtained for eight fetuses diagnosed as abnormal. The volume of seven of the eight abnormal fetuses fell outside the 95% confidence interval established from the data obtained for the normal fetuses. However, for only three of the eight abnormal fetuses did brain volume fall outside the 95% confidence interval established for normals, possibly due to brain sparing occurring in asymmetrical growth retardation. The volume of the fetus and fetal brain may be readily estimated directly using the Cavalieri method and magnetic resonance imaging. These parameters represent potentially useful information for assessing fetal growth.

In 1961 we reported that heterologous kidney antiserum when injected into pregnant rats resulted in wide spectrum of congenital malformations. Further studies identified that it was the IgG component of the antiserum that was teratogenic and that complement was not necessary to produce the teratogenic effect. Labeled antibody studies demonstrated that the kidney antiserum localized in the kidney and in the visceral yolk sac (VYS) and parietal yolk sac placentas. Preparation of yolk sac (YS) antiserum proved to be more potent than the kidney antiserum. Adsorption studies with VYS and parietal yolk sac antiserum revealed that the site of the teratogenic process was located in the VYS. In vitro embryo culture experiments demonstrated that direct injection of the teratogenic antibody into the amniotic or YS cavity did not injure the embryo, thus indicating that the teratogenic antibody had to come in contact with the absorptive surface of the VYS. Collaboration with Dr. John Lloyd demonstrated that teratogenic antibody interfered with the process of pinocytosis and the delivery of amino acids (AA) to the developing embryo. Our studies into the nature of the source of AA for the embryo indicated that in some instances > 95% of the AA present in the developing embryo were derived from maternal proteins and the remainder from free AA in the maternal serum. We also demonstrated that embryonic methionine was derived primarily from the digestion of maternal serum proteins but that more of the methionine was diverted from the synthesis of embryonic proteins, supporting the view that it has important functions other than the synthesis of proteins. All these studies focus on the role of the YS in human development and whether human YS dysfunction may play a role in the pathogenesis of congenital malformations. Further studies on the delivery of AA to the embryo are warranted to determine whether certain AA are in short supply in maternal serum and place the embryo at risk if nutritional alterations in the maternal environment occurs. Furthermore, the YS may be an organ whose role might offer opportunities for pregnancy control.

Objective: To determine whether severe, early-onset intrauterine growth restriction (IUGR) is associated with abnormal umbilical venous pressure (UVP) secondary to increased placental impedance., Methods: 42 singleton fetuses underwent fetal blood sampling from the umbilical vein during evaluation for severe, early-onset IUGR (diagnosed < 32 weeks or symmetrical IUGR diagnosed at any time in gestation). IUGR was confirmed at delivery. The UVP was measured with a solid-state transducer and corrected for amniotic fluid pressure. The ultimate cause of IUGR assigned was based on the antenatal laboratory and postnatal findings. Seven fetuses had a chromosome abnormality, 4 congenital viral infection, 8 miscellaneous causes and 23, by exclusion, uteroplacental (UP) dysfunction. Procedures complicated by fetal bradycardia were excluded because bradycardia raises the UVP., Results: The mean gestation was 31.4 weeks (range 23-38). The umbilical artery resistance index (UA RI) was significantly higher in fetuses with IUGR secondary to either UP dysfunction or a chromosome abnormality compared to the remaining categories of IUGR. The UVP fell outside the 95% confidence interval in only 3 fetuses - 2 with aneuploidy (a 1:7 translocation with a normal UA RI and a mosaic trisomy 21), and 1 with UP dysfunction. The UVP rose with advancing gestation independent of the underlying cause of IUGR. There was an inverse relationship between UVP and the UA RI independent of gestation (r2 = 0.08, p < 0.05). There was an inverse relationship between the UA RI and both the UV pH and PO2 in the fetuses with UP dysfunction. However, there was no relationship between the UVP and either UVpH, UVPCO2, or UVpO2., Conclusions: These findings indicate that placental impedance has little clinically relevant impact on the UVP.

The role of nutrition on the development of the endocrine pancreas was studied in a rat model obtained by maternal food restriction. A 50% food restriction was applied to female rats from day 15 of pregnancy and resulted in intrauterine growth-retardation (IUGR) in the offspring. At day 1 postnatal, beta-cell mass was significantly decreased in IUGR pups as compared to controls (0.70 +/- 0.06 vs 1.07 +/- 0.06 mg, p < 0.0001), as well as insulin content. This change in beta-cell mass can be attributed to a reduced number of islets, since the density of insulin-positive aggregates in pancreatic sections of IUGR rats was 20% lower than in controls. Proliferative capacity of beta cells, as measured by 5-bromo-2-deoxyuridine (BrdU) labelling index, was not altered in growth-retarded animals. Body as well as pancreatic weight were fully recovered in IUGR pups after 21 days of normal feeding by control mothers. However, these animals retained a 25% decrease in insulin content, 40% decrease in beta-cell mass (1.58 +/- 0.18 vs 2.78 +/- 0.42 mg, p < 0.001) and a strong reduction in the density of insulin positive aggregates per cm2, as compared to controls, suggesting that the total islet number was likely to be reduced. Beta-cell proliferative capacity remained normal. In conclusion, in utero undernutrition in rats does not impede postnatal growth but durably impairs beta-cell development. Impairment of beta-cell differentiation might be suggested.

Objective: Our purpose was to assess the effects that fetal growth restriction exerts on the myelination of the developing brain., Study Design: Fetal haemodynamic centralization, an adaptive strategy to growth restriction caused by placental insufficiency, was determined by Doppler ultrasonography. Infants with a raised ratio between umbilical artery pulsatility index and cerebral artery pulsatility index are severely growth restricted. Visual evoked potentials give information on the degree of brain myelination. Shortening of visual evoked potential latencies is a normal feature of myelination. In a consecutive series of 105 Neonates, visual evoked potentials were recorded at the corrected ages of 6 months and 1 years. Correction for possible confounders, such as cranial ultrasonographic findings, gestational age, and head circumference, was performed., Results: At 6 months, infants with a raised umbilical artery/cerebral artery pulsatility index ratio have shorter visual evoked potential latencies. Opposite of neonates with a normal umbilical artery/cerebral artery ratio, they show no postnatal maturational shortening of visual evoked potential latencies., Conclusion: Accelerated neurophysiologic maturation, found in infants with a high umbilical artery/cerebral artery ratio, might be the result of a beneficial adaptive process to severe fetal growth restriction.

The pre- and postnatal findings of a fetus with a de novo del(13)(pter-->q21:) and an occipital encephalocoele are described. Maternal serum alpha-fetoprotein (AFP) screening at 19 weeks' gestation demonstrated a high level of 2.5 multiples of the median (MOM) and ultrasonography at 27 weeks' gestation showed severe intrauterine growth retardation, cardiomegaly, an occipital encephalocoele, and a calvarial defect. Genetic amniocentesis revealed a karyotype of 46,XX,del(13)(pter-->q21:). The proband postnatally displayed additional abnormalities such as microphthalmia, hypertelorism, large low-set ears, and micrognathia. We discuss the association of central nervous system (CNS) malformations with 13q deletions and emphasize that pregnancies with neural tube defects warrant cytogenetic analysis, especially when additional fetal abnormalities and neonatal dysmorphism are observed.

In most mammals studied, a substantial numbers of preimplantation embryos are believed to be lost in vivo. In vitro, embryos develop slowly and lose viability. Hence, there is a need to assess the extent and cause of embryonic loss both in vivo and in vitro. In this study, we assessed the quality of in vivo produced ovulation products/embryos, recovered on days 1-5 pregnancy, from naturally bred wistar rats. From day 1 pregnant rats (n = 24), 226 ovulation products were recovered which included 52% (117) unfertilized oocytes and empty zonae with/without cell debris (UFO-EZ:CD) and 48% (109) 1-cells. Flushings of day 2 rats (n = 27) contained 229 ovulation products, consisting of 70% (160) 2-cells and 30% (69) UFO-EZ:CD. Flushings of day 3 rats (n = 27) had 23% (56) 2-cells, 6% (15) 3-cells, 23% (57) 4-cells, 1% (2) 5-7 cells, 2% (5) 8-cells and 45% (112) UFO-EZ:CD, total being 247. Flushings of day 4 rats (n = 28) had 193 ovulation products comprising of one morula, 45% (86) 8-cells, 5% (9) 5-7-cells and the rest were 4-cells (2), 3-cells (2), 2-cells (1) and 48% (92) UFO-EZ:CD. Day 5 flushings (n = 27) had 202 ovulation products which included 13% (27) morulae, 17% (34) early, 36% (73) mid and 2% (5) late blastocysts; additionally, 4-cells (1), 8-cells (2) and 30% (60) UFO-EZ:CD were also recovered. On day 4, embryos (8-cells) migrated from the oviduct to the uterus. When pregnant rats (n = 25) were allowed to term, only 15 females (60%) delivered pups (128) with variable litter size (2-12). These results indicate that 56% (619/1097) of recovered rat preimplantation embryos are of expected developmental age with a mixture of asynchronously cleaving embryos. The remaining 44% (478) is comprised of 38% (417) UFO-EZ:CD and 6% (61) abnormal and developmentally retarded embryos, which are unlikely to produce viable pups at term.

Marden-Walker syndrome is an autosomal-recessive disorder characterized by psychomotor retardation, blepharophimosis, joint contractures, arachnodactyly, failure to thrive, and, infrequently, renal anomalies. We report on the prenatal diagnosis of Marden-Walker syndrome in a fetus which had had a previously affected sib with this syndrome. The ultrasonic findings indicative of the diagnosis in this fetus were intrauterine growth retardation and renal cystic disease. We emphasize the importance of renal anomalies which, when present in combination with other ultrasound evidence of this syndrome, should be used as a clue for the diagnosis of Marden-Walker syndrome.

The objective of this study was to establish the effect of thyrotropin releasing hormone on the fetal circulation of appropriately grown and growth-retarded fetuses. Doppler recordings were performed immediately before and 15 min after maternal administration of 400 micrograms of thyrotropin releasing hormone in 14 women with appropriately grown and 19 with growth-retarded fetuses. Furthermore, in six women with growth-retarded fetuses, serial recordings were performed at 2-hourly intervals for 8 h until a second thyrotropin releasing hormone dose was administered. Velocity waveforms were recorded from the outflow tracts, inferior vena cava, umbilical artery, middle cerebral artery and descending aorta, and different Doppler indices calculated. In appropriately grown fetuses, thyrotropin releasing hormone induced a significant increase of peak systolic velocity values in the aorta and pulmonary artery and an increase of Doppler-estimated cardiac output. In growth-retarded fetuses, these changes were more evident and associated with a significant decrease in reverse flow in the inferior vena cava during atrial contraction. No changes were observed in fetal heart rate or in the other fetal vessels investigated. In the growth-retarded fetuses followed longitudinally, these changes were evident for the following 8 h and were potentiated by the second thyrotropin releasing hormone administration. In conclusion, thyrotropin releasing hormone induces significant hemodynamic effects on the fetal heart that may temporarily improve the impaired cardiac function of growth-retarded fetuses.

The aim of this study was to compare changes in Doppler ultrasound studies of the fetal circulation in normal pregnancies with a group of pregnancies complicated by proteinuric pregnancy-induced hypertension (PPIH), delivery of a small-for-gestational-age (SGA) baby, or both. A total of 167 uncomplicated pregnancies with a term delivery of an appropriately grown baby (AGA) were used to define the normal range. Altogether, 123 high-risk pregnancies with a known outcome constituted the study group. A color duplex ultrasound machine was used to perform biometry and fetal Doppler studies. Measurements obtained from the fetal circulation included the umbilical artery (UA) pulsatility index (PI), the middle cerebral artery (MCA) PI and time-averaged velocity (TAV), the thoracic aorta (AO) PI and TAV. In addition, the ratio between the MCA PI and UA PI, the MCA PI and the AO PI, and the product of the MCA PI and AO TAV were used in the analysis. A total of 105 pregnancies had a complicated outcome. They were divided into three categories: PPIH only (pregnancies complicated by PPIH with the delivery of an AGA fetus, n = 17), SGA only (delivery of an SGA baby, with no evidence of PPIH, n = 55), and PPIH + SGA (pregnancies complicated by pre-eclampsia and delivery of an SGA baby, n = 37). The PPIH + SGA group represented true clinical intrauterine growth retardation. Cross-sectional reference ranges were created using the observations from the normal group. z-scores (standard deviation from the mean of the normal range) of the last observations made before delivery were calculated for each of the vessel velocimetry measurements and ratios. The statistical significance of z-score values was calculated using analysis of variance. The MCA and UA PI values showed the greatest deviation for any single-vessel parameter. The ratios of fetal Doppler indices (MCA/UA PI ratio, MCA/AO PI ratio and the MCA PI/AO TAV index) demonstrated greater deviation from normal than any individual vessel. The UA PI z-score for PPIH+SGA delivering < 34 weeks gestation (2.92) was significantly greater than the z-score for PPIH+SGA delivering > or = 34 weeks (1.20, p < 0.05). Fetal Doppler indices, in particular ratios that include measurements obtained from the cerebral circulation, help in the recognition of the small fetus that is growth-retarded. At term, evidence of fetal hemodynamic redistribution may exist in the presence of a normal umbilical artery PI. Fetal Doppler indices provide information that is not readily obtained from more conventional tests of fetal well-being.(ABSTRACT TRUNCATED AT 400 WORDS)