Asymmetrical Growth Retardation Research Articles

Comparison of Head Circumference and Abdominal Circumference Ratio in Normotensive and patients with Pregnancy Induced Hypertensive Disorders after 28 weeks of gestation

Background: Hypertensive disorders are an important medical problem of gestation. Hypertensive disorders of pregnancy (HDP) are a significant cause for maternal and fetal morbidity as well as mortality. Intrauterine growth retardation (IUGR) commonly describes the condition of fetus whose size or growth is subnormal. IUGR fetus is frequently described as symmetrical and asymmetrical IUGR in term of their body proportions. Asymmetric growth retardation is typically linked to uteroplacental inadequacy. Hypertension is one of the maternal causes of placental insufficiency. Aim: To compare head circumference and abdominal circumference ratio in normotensive and patients with pregnancy induced hypertensive disorders after 28 weeks of gestation. Methodology: A cross sectional analytical study was carried on 113 pregnant females in which 57 women were normotensive and 56 women were hypertensive. All individuals were scanned by two- dimensional ultrasound following 28 weeks of pregnancy to evaluate sonographic parameters HC and AC. The HC/AC ratio was estimated by dividing head circumference with abdominal circumference. Results: Out of 57 normotensive patients 27 (36.48%) fetuses were diagnosed with IUGR having HC/AC ratio more than 1, while 30 had normal HC/AC ratio. In 56 hypertensive patients 47(63.51%) fetuses were diagnosed with IUGR having HC/AC ratio greater than 1, however 9(23.07%) fetuses had HC/AC ratio within normal range. So out of total 113 patients, 74 fetuses were found with IUGR while 39 fetuses had HC/AC ratio within normal ranges. Our study found that a cut off value of ≥ 1.0974 for HC/AC ratio could be used as diagnostic parameter in predicting IUGR. Conclusion: HC/AC ratio is a useful parameter for the detection of IUGR. Keywords: Head Circumference, Abdominal Circumference, Intra Uterine Growth Retardation

Asymmetrical fetal growth is not associated with altered trophoblast apoptotic activity in idiopathic intrauterine growth retardation

To investigate whether there is difference in trophoblast apoptosis between infants with asymmetrical idiopathic intrauterine growth retardation (IUGR) and those with symmetrical fetal growth appropriate for gestational age (AGA). Data and placentas from 52 singleton term pregnancies with idiopathic IUGR, from which a subgroup of 33 (63.4%) infants with asymmetrical growth and malnutrition was identified using the ponderal index served as a study group. The control group included 60 (86.9%) infants with symmetrical growth, identified by the same criterion among 69 normal singleton pregnancies with AGA. IUGR was defined by birthweight less than the 10th percentile of standard values. Ponderal index value was considered as the measurement of fetal growth proportionality. The proportion of fetal thinness up to ponderal index value was greater in the IUGR group than control (χ(2) = 9.2; P = 0.002). There was no statistically significant difference in the cytotrophoblast proliferation (t = 0.88; P = 0.373), trophoblast expression of the Bcl-2 anti-apoptotic factor (z = 0.66; P = 0.505), total trophoblast apoptotic index (t = 0.45; P = 0.651), as in cytotrophoblast (t = 0.01; P = 0.988) and syncytiotrophoblast apoptotic index (t = 0.34; P = 0.730) between the idiopathic asymmetrical IUGR and control group. Asymmetry of fetal growth is a result of rather long-term placental nutritive insufficiency in which trophoblasts have a central role. Although being crucial for its functioning, the proliferative and apoptotic trophoblast activity remains unaltered in the placentas from pregnancies with idiopathic IUGR and asymmetrical fetal growth. The results obtained in this study indicate that placental nutritive insufficiency may develop without any deviation in the physiological trophoblast regeneration via apoptosis.

Prenatal programming in an obese swine model: sex-related effects of maternal energy restriction on morphology, metabolism and hypothalamic gene expression

Maternal energy restriction during pregnancy predisposes to metabolic alterations in the offspring. The present study was designed to evaluate phenotypic and metabolic consequences following maternal undernutrition in an obese pig model and to define the potential role of hypothalamic gene expression in programming effects. Iberian sows were fed a control or a 50 % restricted diet for the last two-thirds of gestation. Newborns were assessed for body and organ weights, hormonal and metabolic status, and hypothalamic expression of genes implicated in energy homeostasis, glucocorticoid function and methylation. Weight and adiposity were measured in adult littermates. Newborns of the restricted sows were lighter (P <0·01), but brain growth was spared. The plasma concentration of TAG was lower in the restricted newborns than in the control newborns of both the sexes (P <0·01), while the concentration of cortisol was higher in females born to the restricted sows (P <0·04), reflecting a situation of metabolic stress by nutrient insufficiency. A lower hypothalamic expression of anorexigenic peptides (LEPR and POMC, P <0·01 and P <0·04, respectively) was observed in females born to the restricted sows, but no effect was observed in the males. The expression of HSD11B1 gene was down-regulated in the restricted animals (P <0·05), suggesting an adaptive mechanism for reducing the harmful effects of elevated concentrations of cortisol. At 4 and 7 months of age, the restricted females were heavier and fatter than the controls (P< 0·01). Maternal feed restriction induces asymmetrical growth retardation and metabolic alterations in the offspring. Differences in gene expression at birth and higher growth and adiposity in adulthood suggest a female-specific programming effect for a positive energy balance, possibly due to overexposure to endogenous stress-induced glucocorticoids.

A 2 Mb deletion in 14q13 associated with severe developmental delay and hemophagocytic lymphohistiocytosis

Interstitial deletions of chromosome 14 have rarely been described. We report on a boy in whom a 2 Mb deletion in 14q13 was discovered by array CGH. The deletion was a de novo event. The boy presented with asymmetrical growth retardation at birth. There was severe developmental delay with muscular hypotonia and focal epilepsy with apneic episodes progressing to serial tonic seizures. At the age of 3 3/12 years he was diagnosed with pneumonia. In the further course he developed symptoms of hemophagocytic lymphohistiocytosis. He died due to organ failure. Herein the clinical findings are compared to patients with cytogenetic visible deletions encompassing the region deleted in the proband and the possible connection with the deleted genes.

Triploidy: 109 Prenatal Diagnoses

Triploidy is a common finding both in early spontaneous miscarriages and in the fetal period, presenting in 1–2% of pregnancies. It may be the result of diandry (an extra paternal haploid set) or digyny (an extra maternal haploid set). Diandry predominates in cases of triploidy without embryos after nine weeks or in the second trimester with fetuses of relatively normal size and with placental findings of partial hydatidiform mole. Digyny predominates in early miscarriages before nine weeks with embryos or in the second trimester with fetuses with a marked asymmetrical intrauterine growth retardation and a small placenta. We reviewed 109 prenatal diagnoses of triploidy in a ten-year period. In the group with the first trimester diagnosis &lt;14 weeks ( n=62), an interesting finding is the high percentage of recurrent miscarriage as an indication for chromosomal analysis ( n=26/62; 42%). In the second and third trimesters &lt;14 weeks ( n=47), 29 cases had ultrasound characteristics of digynic triploidy with an asymmetrical fetal growth retardation with oligohydramnios of which three pregnancies continued above 20 weeks with abnormal Doppler waveforms and velocities. Thirteen cases had ultrasound characteristics of diandric triploidy with only mild growth retarded or normal grown fetuses with a thickened placenta. Other indications for chromosomal analysis were maternal age ( n=1) and a positive maternal serum triple test screening without ultrasound specifications ( n=4). Early prenatal recognition of triploid pregnancies, certainly those with placental findings of partial hydatidiform mole, is important since these mothers are at risk of preeclampsia and persistent trophoblastic disease.

The Mechanisms of Low Birth Weight in Infants of Mothers With Homozygous Sickle Cell Disease

A low mean birth weight is a constant finding in pregnancies of women with homozygous sickle cell disease. The factors responsible are largely unknown and have now been investigated in an 11-year retrospective analysis. Records for 126 pregnancies of mothers with homozygous sickle cell disease and 126 pregnancies of control women with an AA phenotype, matched according to age and date of delivery, were examined. Events during pregnancy and outcomes of pregnancy were recorded. Pregnancy outcomes for mothers with homozygous sickle cell disease confirmed the lower birth weight, gestational age, and placental weight. A low birth weight in infants of mothers with homozygous sickle cell disease was strongly related to gestational age and placental weight and weakly related to reticulocyte counts and a history of preeclampsia in univariate analyses, but only gestational age and placental weight remained significant in multivariate analyses. No relationships were seen with maternal age, parity, anthropometric features, other hematologic features (hemoglobin levels, fetal hemoglobin levels, mean cell volume, and alpha-thalassemia), pregnancy-induced hypertension, or prepartum hospital admissions (expressed as number or total days). Compared with Jamaican standards, birth weight was affected more than head circumference or length in infants of mothers with homozygous sickle cell disease, indicating asymmetric growth retardation, which occurred for 27% of boys and 38% of girls (compared with 4% and 9%, respectively, among infants of control mothers). A chronic condition such as homozygous sickle cell disease might have been expected to cause symmetric growth retardation throughout pregnancy. The finding of asymmetric retardation might indicate adverse factors emerging late in pregnancy and might have relevance for the poor pregnancy outcomes in such mothers.

A novel case of Silver Russell Syndrome (SRS) and male breast cancer

21178 Introduction: Silver Russell Syndome (SRS) is a heterogeneous disorder of asymmetric growth retardation and typical dysmorphic features often associated with maternal disomy 7 and chromosome 17q23–24. The BRCA1 gene is found on 17q21. The relationship between SRS and breast cancer has not been described to date. Case Presentation: We report a case of a 37 year old male diagnosed with metastatic breast cancer involving the liver and bone. Patient presented with a left proximal hip fracture related to metastatic bone disease. Biopsy of the right breast lesion revealed a moderately differentiated adenocarcinoma consistent with breast primary. Abdominal ultrasound and full body bone scan revealed extensive liver and bone metastases. There was no significant family history of cancer, specifically breast nor ovarian cancer. Discussion: The BRCA2 gene is known to be responsible for DNA repair. The SRS cases associated with chromosome 17q24–25 abnormalities are known to be associated with growth hormone deletions. Further investigations into this relationship are warranted. No significant financial relationships to disclose.

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.

Die Magnetokardiographie - eine mögliche ergänzende Methode zur Früherkennung einer fetalen Gefährdung in Risikoschwangerschaften

Ever since the first report on fetal magnetocardiography by Kariniemi in 1974 numerous studies have examined cardiac activity in healthy fetuses using this technique. Recently there has been an increase in reports on the identification of fetal pathological states, in particular in the diagnosis of fetal arrhythmias, using magnetocardiography. Other possible applications of this non-invasive method include the assessment of intrauterine growth retardation and fetal stress. In a patient with gestational hypertension and asymmetric growth retardation without pathological ultrasound findings, fetal magnetocardiography showed a reduced beat-to-beat heart rate variability indicating signs of fetal stress. On the day following the magnetocardiographic recording, fetal Doppler ultrasonography findings indicated an incipient brain sparing effect. The fetal growth retardation was reflected in the duration of the fetal cardiac time intervals. We conclude that fetal magnetocardiography non-invasively enables the timely identification of pathological fetal conditions.

Perfil lipídico en recién nacidos con retardo del crecimiento intrauterino

The X syndrome, related to coronary disease in adults, could be possibly programmed priory to delivery, in children with intrauterine growth retardation. To measure serum lipids in newborns with symmetrical or asymmetrical intrauterine growth retardation. One hundred thirty-five newborns with intrauterine growth retardation and 116 normal term newborns, with 38 to 41 gestational weeks, were studied. Total, HDL, and LDL cholesterol, triglycerides and apoproteins. A1 and B were measured in umbilical cord blood samples. No differences in total, HDL, LDL cholesterol, apoproteins A1 and B were observed between the study groups. Triglycerides were higher in newborns with intrauterine growth retardation, compared to normal term newborns (45 +/- 27 and 36 +/- 19 mg/dl respectively, p < 0.001). Differences in serum triglyceride levels respect to controls were observed in both male and female newborns with asymmetrical growth retardation. Likewise the differences respect to controls were observed in newborns with mild or severe but not with moderate growth retardation. Newborns with intrauterine growth retardation have higher triglyceride levels than normal term newborns.

Wedge-Shaped Distal Tibial Epiphysis in the Pathogenesis of Equinovalgus Deformity of the Foot and Ankle in Tibial Lengthening for Fibular Hemimelia

Fibular hemimelia is associated with an equinovalgus deformity of the foot and ankle and different degrees of wedging of the distal tibial epiphysis. This deformity is often a major problem during lengthening of the shortened tibia. To determine the significance of the wedge-shaped distal tibial epiphysis in the pathogenesis of the equinovalgus deformity of the foot and ankle during and after lengthening, we reviewed 20 patients who had undergone tibial lengthening by either the Wagner or the Ilizarov technique. The mean duration of follow-up after removal of the fixator was 5.2 years (range, 2.3-9.7 years). Three types of wedge-shaped distal tibial epiphyses were identified. A mildly wedged (type I) epiphysis was found in seven patients, a moderately wedged (type II) epiphysis was found in seven patients, and a severely wedged (type III) epiphysis, in six patients. Premature fusion of the lateral part of the distal tibial physis and growth retardation of the tibia were common after lengthening in patients with the type II or type III epiphysis. After lengthening, all patients with a type II or type III epiphysis had a recurrence or aggravation of foot deformities that existed before lengthening. This usually necessitated various secondary operative procedures to obtain a plantigrade foot. We believe that after lengthening, one should anticipate varying degrees of mild growth retardation and minimal foot deformity in patients with type I epiphysis, worsened asymmetric growth retardation and progressive foot deformity in patients with type II epiphysis, and severe growth retardation and severe foot deformity in patients with type III epiphysis.

Plasmodium coatneyi in the rhesus monkey (Macaca mulatta) as a model of malaria in pregnancy.

Pregnant women with Plasmodium falciparum infection are at increased risk for complications such as anemia and cerebral malaria. In addition, the infants of these women suffer intrauterine growth retardation (IUGR), low birth weight (LBW), congenital infection, and high infant mortality. Although much has been learned from studies of malaria during human pregnancy, progress has been limited by the lack of a suitable animal model. Nonhuman primates are of particular interest because, other than the armadillo, they are the only animals with a discoidal, villous, hemochorial placenta like that of humans. We have established a model of malaria during human pregnancy by inoculating pregnant rhesus monkeys (Macaca mulatta) with Plasmodium coatneyi (a sequestering parasite) during the first trimester. In our initial experiment, four monkeys were inoculated with a fresh inoculum containing 10(8) viable parasites from an infected donor monkey. All four monkeys became parasitemic seven days postinoculation (PI) and three monkeys aborted 7-10 days PI coincident with high peak parasitemias (41,088-374,325 parasites/mm3). Although abortion is one of the outcomes observed in Plasmodium-infected women, the intent of this study was to examine the effects of Plasmodium infection throughout gestation. Since the rapid onset of high parasitemia may have been responsible for the abortions, a decision was made to reduce the size of the effective inoculum. Six additional pregnant monkeys were inoculated with a frozen isolate taken from the same donor containing 10(6) parasites. These six animals became parasitemic by 14 days PI and, along with monkey E412, carried their infants to term. These seven infants weighed significantly less at term than the infants of uninfected mothers (P = 0.0355). Symmetrical IUGR was detected by ultrasound in one fetus with an LBW of 334 g. Another LBW infant (300 g) had asymmetrical growth retardation, which has been associated with uteroplacental insufficiency and was consistent with the lower placental weights found in infected dams compared with controls (P = 0.0455). The infant with symmetric IUGR died at five days of age, while the other is alive but congenitally infected. The IUGR, LBW, congenital infection, postnatal infant mortality, and early abortions observed in these animals suggest that P. coatneyi in pregnant rhesus monkeys is a valid model of malaria in human pregnancy. This model should provide the opportunity to study questions about malaria in pregnancy that have been difficult to study in humans.

Catecholamines inhibit growth in fetal sheep in the absence of hypoxemia.

To evaluate contributions of catecholamines to inhibition of growth during chronic hypoxemia or severe undernutrition, epinephrine (Epi; 0.25-0.35 microg . kg-1 . min-1) or norepinephrine (NE; 0.5-0.7 microg . kg-1 . min-1) was administered to normoxemic fetuses in twin-pregnant ewes for 8-12 days, from 125 to 127 days of gestation. Both had similar effects and decreased fetal weight by approximately 20% relative to control twins (P < 0.01). Weight gain ceased during infusion of Epi or NE (-21 +/- 14.8 or 14 +/- 20.9 g/day), whereas controls gained 93 +/- 13.2 g/day (P < 0.01). Effects on tissues and organs varied, spleen and thymus being most retarded, whereas brain weight and skeletal measures were affected little. Selected muscles from infused fetuses weighed 72% of those in controls. Growth ceased during infusion (P < 0.001). Weight gain of hindlimb bones was negligible, but length increased at 56% of control rates. Arterial blood CO2 and plasma insulin were decreased (P < 0.001), but plasma glucose, growth hormone, and blood oxygenation increased (P < 0.001). Actions of Epi and NE could underlie asymmetrical growth retardation occurring in many adverse physiological situations during fetal development.

Does Growth Rate Differ Between Symmetrical vs Asymmetrical Small-for-Gestation (SGA), Extremely Low-Birth Weight (ELBW;&lt;1000 gm) Infants? 1554

SGA infants are at risk for poor postnatal growth and this is especially true in infants who have symmetrical intratuterine growth retardation (SYM; wt, ht & ofc <10th%ile) versus infants with asymmetrical growth retardation (ASYM; wt<10th%ile; ht & ofc 10-90th%ile). SYM indicates growth retardation that begins to occur early in pregnancy, while ASYM more often represents growth retardation that occurs in late pregnancy. It is unknown how SYM vs ASYM growth retardation effects postnatal growth in preterm, ELBW infants.

Fetal and Fetal Brain Volume Estimation in the Third Trimester of Human Pregnancy Using Gradient Echo MR Imaging

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 10–90 th 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 (R 2 = 0.88) and between fetal brain volume and gestational age (R 2 = 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.

Body weight distribution and organ size in newborn swine (sus scrofa domestica) — A study describing an animal model for asymmetrical intrauterine growth retardation

Normal growth is the expression of the genetic potential to growth which is neither abnormally constrained nor promoted by internal or external factors. Restricted fetal growth is common in human pregnancy and is associated with increased perinatal morbidity and mortality. Because of ethical restrictions, pathogenetical studies are necessarily dependent on appropriate animal models. In the studies presented, evidence will be provided that the naturally occurring distribution of body weight in newborn piglets, obtained from n = 512 newborn piglets (about 12 hours old) in 50 consecutive deliveries in the breed cohort of the mixed German domestic breed - "Deutsches Land-/Edelschwein" gives an appropriate sampling for providing a statistically reliable basis with which to determine different degrees of fetal growth for further pathophysiological studies intended. A strong inverse correlation (r = -0.66, p < 0.05) was found between the mean weight of the litter and the number of piglets per litter, and an inverse correlation (r = -0.64, p < 0.05) was found between the lowest weight of the littermate and the number of piglets per litter. Moreover, gravimetric investigations were made into an additional 53 one-day-old newborn piglets reflecting the naturally occurring birth weight distribution determined. A marked linear correlation between body weights and various organ weights was found (values of the correlation coefficient amounted to between 0.45 and 0.98; p < 0.05). The lowest variation of organ weights was found in the CNS structures (0.68-1.33). Skeleton and heart exhibited similar ranges of weight variation (0.35-1.81 and 0.38-2.00 of the means) to body weight (0.38-1.77 of the means). This was also expressed in the regression analysis, because the slope values were 0.99 and 0.97 respectively. The hormonal glands investigated, the kidneys, and the abdominal parenchymal organs exhibited the largest ranges of weight variation. Moreover, regression analysis gives evidence that the weight restriction was more pronounced than expected concerning respective body weight. This is indicated by slope values > 1 in almost all of those organs. Plasma concentration of IGF-1 showed an inverse correlation with body weight (r = -0.42; p < 0.05, fig 4). IGF-1 concentration of intrauterine growth retarded (IUGR) newborn piglets was in the mean nearly double that of normal weight animals (p < 0.05) and the brain weight to liver weight ratio was increased more than 2.5 times in IUGR newborn (fig 5 A, p < 0.05). This investigation provides information on the naturally occurring body weight distribution of one-day-old piglets, which was obviously a result of epigenetic factors. Gravimetrical estimation showed clearly that body weight variety is most probably caused by alterations of placental functioning. Severe alterations resulted in asymmetrical growth retardation, which was proved by a significantly increased brain to liver ratio in animals with a body weight < 10th centile. Thus, evidence is provided that naturally occurring asymmetrical intrauterine growth restricted newborn piglets can be identified simply by body weight measurement, so that convenient conditions are given for pathogenetically motivated studies on intrauterine compromised newborns.

Prenatal growth in symmetric and asymmetric small-for-gestational-age infants.

We tested the hypothesis that growth retardation in symmetric small-for-gestational-age (SGA) infants may start in the first trimester of pregnancy, whereas in asymmetric SGA infants, it may start in the third trimester. We also examined if there may be a brain sparing effect in asymmetric SGA infants. Infants were classified as symmetric or asymmetric SGA infants, and 474 non-SGA infants. Intrauterine growth was assessed by prenatal ultrasonic measurements of fetal abdominal diameter, femur length and biparietal diameter at week 17, 25, 33 and 37 of gestation. Cross-sectional data as well as longitudinal growth curves suggested that growth retardation in both SGA groups started in the second trimester, and followed similar patterns until birth. Thus, our results did not support the hypothesis that symmetric and asymmetric growth retardation is associated with clear temporal differences in growth, and we found no sign of brain sparing in asymmetric compared to symmetric SGA infants.

Effects of intrauterine growth retardation in premature infants on early childhood growth

Objective: To evaluate in preterm infants the role of intrauterine growth retardation and infant body proportionality on subsequent childhood growth. Methods: Preterm infants (818) prospectively enrolled in the Infant Health and Development Program were studied from birth to 36 months of corrected age. Weights and lengths were recorded at eight intervals. Growth parameters were compared in preterm infants with differing body symmetry at birth, defined by length-for-age and weight-for-age. Infants with both low length-for-age and low weight-for-age at birth were categorized as symmetrically growth retarded, and infants with normal length-for-age and low weight-for-age were categorized as asymmetrically growth retarded. Results: Infants born with low length-for-age demonstrated increased growth velocity until 8 months of corrected age ( p <0.001). However, infants born with low weight-for-age demonstrated decreased weight-gain velocity compared with preterm infants with appropriate weight for gestational age (AGA) until 40 weeks of corrected age ( p <0.001). Heights and weights of infants with either symmetric or asymmetric intrauterine growth retardation remained significantly retarded compared with AGA preterm patients and the National Child Health Survey (NCHS) reference population ( p <0.001). Infants born short but with normal weight did not significantly differ from AGA preterm infants in either weight or length at 36 months of corrected age. Preterm infants with both symmetric and asymmetric growth retardation demonstrated limited catch-up growth in weight until age 4 months and then paralleled the AGA preterm patients and the NCHS reference population. Very low birth weight (≤1250 gm), gestational age, and a broad-based day-care intervention did not influence growth outcome after control for the presence of intrauterine growth retardation. Conclusions: Preterm infants with both symmetric and asymmetric intrauterine growth retardation demonstrate limited catch-up growth. Intrauterine growth deficits persist into early childhood. (J Pediatr 1997;130:95-102)

Early asymmetric IUGR and aneuploidy.

To determine the incidence of chromosomal abnormalities in fetuses with asymmetric growth retardation in the second and early third trimesters of pregnancy. From November 1989 to December 1993, 71 singleton pregnancies with asymmetrical growth retardation diagnosed at 15 to 35 weeks gestation had detailed ultrasonographic examination for structural malformations and fetal karyotyping done. The fetal karyotype was abnormal in 7 (9.9%) of the cases. There were 19 growth retarded fetuses with concomitant structural defects. The incidence of chromosomal abnormalities in asymmetrical growth retarded fetuses with structural defects was 21% (4/19). The incidence of fetal aneuploidy in structurally normal fetuses with asymmetrical growth retardation detected before 23 weeks gestation was 20% (3/15); while for those presenting between 23-29 weeks gestation, no abnormal karyotypes were found. Although more prospective data is needed, our data seems to suggest that fetal karyotyping may be unnecessary in structurally normal fetuses with early onset intrauterine growth retardation occurring between 23-29 weeks of gestation.

784-1 The Effect of Prenatal Cyclosporine on Fetal Rabbit Growth and the Myocardial Beta Adrenergic Receptor-Cyclic AMP Pathway

As the pediatric and adolescent survivors of organ transplantation reach reproductive age, there will be an increasing number of fetuses exposed to cyclosporine (CSA) throughout gestation. The effect of CSA on the developing fetus has received little attention. We studied the effect of prenatal CSA administration on fetal rabbits’ growth and the myocardial beta adrenergic receptor-cyclic AMP pathway. Pregnant New Zealand white rabbits were treated either with subcutaneous CSA, 20/mg/kg twice weekly, or placebo, starting at 14 days gestation. At 29 days gestation (term 30 days), the fetuses were delivered by cesarian section. Maternal and fetal organs were weighed and fetal myocardium processed and stored. Beta adrenergic receptor numbers were determined by competitive binding assay using radiolabelled Dihydro-alpranolol. Cyclic AMP production was measured using radioenzymatic assay. Statistical comparisons utilized unpaired Student's t-test. CSA administration did not alter maternal body or organ growth. In the rabbit pups, body, heart, lung and kidney weights were decreased to 75% of control (p &lt; 0.0001). Liver weight was decreased further to 68% of control (p &lt; 0.0001 compared to controls, p &lt; 0.03 compared to body and other organ weight reductions). Despite the reduction in myocardial growth, beta adrenergic receptor numbers and cyclic AMP production were not different in the CSA treated group. Prenatal CSA administration results in asymmetric growth retardation in the rabbit fetus. The beta adrenergic receptor-cyclic AM P pathway does not appear to be altered. Because CSA is currently not contraindicated during human pregnancy, the effects on the fetus deserve further study.