Impaired Postnatal Growth Research Articles

Inhaled nitric oxide to prevent bronchopulmonary dysplasia in preterm neonates

Bronchopulmonary dysplasia is a chronic lung disease that affects premature infants and contributes to their morbidity and mortality. With the advent of prenatal steroids and postnatal exogenous surfactant and less aggressive respiratory support, premature infants can develop chronic oxygen dependency without even acute respiratory distress. This 'new bronchopulmonary dysplasia' could be the result of impaired postnatal growth. Several experimental studies have suggested a possible role of the vascular endothelial growth factor/nitric oxide (VEGF/NO) pathway in restoring pulmonary angiogenesis and enhancing distal lung growth. The results of the clinical studies are, however, inconclusive, and it is currently unclear which subsets of premature infants might benefit from inhaled nitric oxide. Besides, severe intracranial haemorrhage and/or cystic periventricular leucomalacia may affect the most immature babies, many of whom are spared from severe initial respiratory disease. Recently, inhaled nitric oxide was shown to significantly decrease the incidence of these neurological events, and to improve the long-term outcome in a few clinical trials. At times neuroprotective, at times neurotoxic, nitric oxide is capable of divergent effects depending upon the extent of cerebral damage, the redox state of the cell, and the experimental model used. Recently, our group found that inhaled nitric oxide had remote effects including angiogenesis and maturation on the developing brain in rodent pups. Thus, we await the results of the recently completed randomised clinical trial of inhaled nitric oxide to prevent bronchopulmonary dysplasia (the European Nitric Oxide or 'EUNO' trial) where, besides the primary endpoint of chronic oxygen dependency reduction at 36 weeks' postconceptional age, long-term lung and brain will be followed-up until 7 years of age.

P38.09: Prenatal sonographic findings in a case of cardio‐facio‐cutaneous syndrome

The differential diagnosis of the karyotypically normal fetus with cystic hygromas is extensive, and includes several syndromes for which DNA diagnosis can now be done. We present a case in which cystic hygromas had been seen at 17 weeks. Karyotyping was normal. On our initial sonogram, at 21 weeks, findings included cystic hygroma, anteriorly displaced aorta, prominent superior vena cava, and globular appearance to the left ventricle. Polyhydramnios and a protruberant fetal tongue developed in the third trimester. Delivery was prompted by cessation of fetal movement at 32 weeks gestation. Cord blood gas studies were normal. The infant had dysmorphic features and hypotonia and developed progressive cardiomyopathy with pulmonic stenosis and concentric biventricular hypertrophy. Differential diagnosis included Noonan, Costello, and CFC syndromes. The neonate subsequently expired. When DNA testing for CFC became available, a stored specimen was checked, and demonstrated a heterozygous missense mutation (c.1931 G > T) in exon 11) of the BRAF gene consistent with the diagnosis of CFC syndrome. Cardio-facio-cutaneous (CFC) syndrome is a rare, devastating, sporadic syndrome which has recently been linked to gain-of-function mutations in the BRAF, KRAS, MEK1 and MEK2 genes of the RAS-extracellular signal-regulated kinase pathway. Abnormalities include developmental delay, postnatal growth impairment, characteristic facial features (prominent forehead, temporal narrowing, hypotelorism, posteriorly rotated ears) with or without web neck, cutaneous manifestations (sparse brittle hair, absent eyebrows, and hyperkeratosis of the palms and soles), and a variety of cardiac anomalies, including pulmonic stenosis and hypertrophic cardiomyopathy, often manifest only after birth. In utero diagnosis has not been described. Whether the unique cardiac findings described here will be seen in other cases awaits further sonographic observations. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Growth of cranial synchondroses and sutures requires polycystin-1

In vertebrates, coordinated embryonic and postnatal growth of the craniofacial bones and the skull base is essential during the expansion of the rostrum and the brain. Identification of molecules that regulate skull growth is important for understanding the nature of craniofacial defects and for development of non-invasive biologically based diagnostics and therapies. Here we report on spatially restricted growth defects at the skull base and in craniofacial sutures of mice deficient for polycystin-1 ( Pkd1). Mutant animals reveal a premature closure of both presphenoid and sphenooccipital synchondroses at the cranial base. Furthermore, knockout mice lacking Pkd1 in neural crest cells are characterized by impaired postnatal growth at the osteogenic fronts in craniofacial sutures that are subjected to tensile forces. Our data suggest that polycystin-1 is required for proliferation of subpopulations of cranial osteochondroprogenitor cells of both mesodermal and neural crest origin during skull growth. However, the Erk1/2 signalling pathway is up-regulated in the Pkd1-deficient skeletal tissue, similarly to that previously reported for polycystic kidney.

Growth patterns in the growth-retarded premature infant

Approximately 10% of all infants are born prematurely. A large proportion of these infants show evidence of postnatal growth impairment irrespective of whether birth weight was appropriate or small for gestational age. The timing and magnitude of catch-up growth is very variable, with the most immature infants showing markedly delayed catch up which is often incomplete. Long-term studies suggest that final stature may be affected significantly. Growth impairment in itself is of concern and there are suggestions that this group of infants should be eligible for growth hormone treatment. However, in addition, there is increasing evidence to suggest that there should be additional concerns in this group of infants, as abnormal early growth may influence disease susceptibility in adult life. This review assesses the patterns of postnatal growth and the possible later implications of early aberrant growth patterns in later life.

Pregnancy Outcome and Placenta Pathology in Plasmodium berghei ANKA Infected Mice Reproduce the Pathogenesis of Severe Malaria in Pregnant Women

Pregnancy-associated malaria (PAM) is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth retardation, low birth weight and infant mortality. The physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. Here, we describe a comprehensive mouse experimental model that recapitulates many of the pathological and clinical features typical of human severe malaria in pregnancy. We used P. berghei ANKA-GFP infection during pregnancy to evoke a prominent inflammatory response in the placenta that entails CD11b mononuclear infiltration, up-regulation of MIP-1 alpha chemokine and is associated with marked reduction of placental vascular spaces. Placenta pathology was associated with decreased fetal viability, intra-uterine growth retardation, gross post-natal growth impairment and increased disease severity in pregnant females. Moreover, we provide evidence that CSA and HA, known to mediate P. falciparum adhesion to human placenta, are also involved in mouse placental malaria infection. We propose that reduction of maternal blood flow in the placenta is a key pathogenic factor in murine pregnancy malaria and we hypothesize that exacerbated innate inflammatory responses to Plasmodium infected red blood cells trigger severe placenta pathology. This experimental model provides an opportunity to identify cell and molecular components of severe PAM pathogenesis and to investigate the inflammatory response that leads to the observed fetal and placental blood circulation abnormalities.

Polymorphisms Identified in the Upstream Core Polyadenylation Signal ofIGF1Gene Exon 6 Do Not Cause Pre- and Postnatal Growth Impairment

Few children born small for gestational age (SGA) with IGF1 mutations have been reported. One of these patients presented a mutation at 3' untranslated region (UTR) at exon 6, probably affecting the polyadenylation process. The objective of the study was to sequence the IGF1 gene of children born SGA. IGF1 (exons 1-6) was directly sequenced in 53 SGA children without catch-up growth. Allelic variant frequency of the identified IGF1 polymorphisms was assessed in a total of 145 SGA children and in 180 controls born with adequate weight and length and adult height sd score greater than -2. No mutations were identified in the IGF1 coding regions in SGA children. In contrast, six allelic variants were identified in the upstream core polyadenylation signal located in IGF1 3' UTR at exon 6. The frequency of the different allelic variants was similar in SGA children and controls. It is noteworthy that the same allelic variant, previously described as causing severe IGF1 deficiency, was also observed in homozygous (n = 4) and heterozygous state (n = 6) in normal height controls, corresponding to 4% of studied alleles. The three most frequently identified allelic variants of IGF1 3' UTR showed no effect on height sd score of adult controls as well as on birth characteristics in SGA children. The polymorphisms identified in the upstream core polyadenylation signal at IGF1 exon 6 do not cause IGF1 deficiency as well as pre- and postnatal growth impairment, in contrast to previously reported data.

Heterozygote Effects in Mice with Partial Truncations in the Growth Hormone Receptor Cytoplasmic Domain: Assessment of Growth Parameters and Phenotype

The GH receptor (GHR) is essential for normal postnatal growth and development, and the molecular basis of GHR action has been studied intensively. Clinical case studies and more recently mouse models have revealed the extensive phenotype of impaired GH action. We recently reported two new mouse models, possessing cytoplasmic truncations at position 569 (plus Y539/545-F) and 391, which were created to identify functional subdomains within the cytoplasmic signaling domain. In the homozygous state, these animals show progressively impaired postnatal growth coupled with complex changes in gene expression. We describe here an extended phenotype analysis encompassing the heterozygote state to identify whether single copies of these mutant receptors bring about partial or dominant-negative phenotypes. It appears that the retention of the ubiquitin-dependent endocytosis motif in the N-terminal cytoplasmic domain permits turnover of these mutant receptors because no dominant-negative phenotype is seen. Nonetheless, we do observe partial impairment of postnatal growth in heterozygotes supporting limited haploinsufficiency. Reproductive function is impaired in these models in a progressive manner, in parallel with loss of signal transducer and activator of transcription-5 activation ability. In summary, we describe a more comprehensive phenotypic analysis of these mouse models, encompassing overall and longitudinal body growth, reproductive function, and hormonal status in both the heterozygote and homozygote state. Our results suggest that patients expressing single copies of similarly mutated GHRs would not display an obvious clinical phenotype.

Gastrointestinal phenotype of GAD67lacZ transgenic mice with early postnatal lethality.

It has been proposed that gamma-aminobutyric acid (GABA) in the gut may function as a neurotransmitter, hormone and/or paracrine agent. Our aim was to examine transgenic mice of the GAD67-lacZ line with impaired postnatal growth and early postnatal lethality for gastrointestinal abnormalities. The gastrointestinal tract was dissected and processed for histology, immunohistochemistry, electron microscopy, western blotting and measurement of GAD activity. Homozygous mice of both sexes displayed an intestinal phenotype characterized by a fragile and haemorrhagic intestinal wall, a reduced number of villi, epithelial lesions and the occasional appearance of pseudostratified epithelium. The number of GABA-immunoreactive enteroendocrine cells and mucin-secreting goblet cells increased significantly relative to wild-type epithelium. The appearance of GABA-immunopositive neuronal perikarya and the lack of GABA-immunoreactive varicose fibres were observed in the enteric plexuses of transgenic mice. Tissue homogenates of transgenic mice showed higher levels of expression of GAD67 and GAD65 as compared with wild-type mice. Our results suggest that the possible reason underlying the growth impairment and postnatal lethality observed in GAD67 transgenic mice is a functional impairment of GABAergic enteric neurons and disintegration of intestinal epithelium.

Evaluation of the Auxological and Metabolic Status in Prepubertal Children Born Small for Gestational Age

Low birth weight (BW) (<2,500 g) is associated with a high risk of impaired postnatal growth and late metabolic consequences. The aim of this study is to describe the postnatal growth pattern and the metabolic status of children born small for gestational age (SGA) and compare them with premature children born with low (1,500-2,500 g) and very low (<1,500 g) BW. 104 prepubertal children (47 males and 57 females) aged 3.0 to 8.9 years were divided into four groups according to their birth weight adjusted for gestational age (GA): SGA-premature (SGApr): BW < -2 SD, GA <37 wk (n = 17); SGA-full-term (SGAt): BW < -2 SD, GA >37 wk (n = 29); low birth weight (LBW): BW = 1,500-2,500 g, GA <37 wk (n = 35); very low birth weight (VLBW): BW <1,500 g, GA <37 wk (n = 23). The control group consisted of 27 full-term appropriate for gestational age, prepubertal children matched for age. All children had anthropometric and laboratory measurements. The HOMA model was used to estimate insulin resistance (IR). Weight, height and body mass index (BMI) were significantly lower in the SGA groups -- both term and premature -- (p <0.05) and particularly lower in the VLBW children (p <0.01). At the age of 36 months, 99.6% of SGAt and a smaller percentage of SGApr (88.2%) children achieved catch-up growth. IGF-I and IGFBP-3 levels were lower in the children born SGA, both term and premature, compared to the controls (p <0.05) and especially in those who had catch-up after the age of 6 months (p <0.002). VLBW children aged 6-8.9 years had significantly higher HOMA compared to controls of the same age group (p = 0.005), whereas no evidence of IR was found in the SGA children. None of the children had developed premature adrenarche by the day of examination. Prepubertal children born SGA and VLBW are thinner and shorter than their age-matched controls. A larger percentage of SGA full-term children achieve catch-up growth than SGA premature children by 3 years of age. SGA children and especially those with late catch-up growth have lower IGF-I levels. Children with VLBW show evidence of IR at age 6-8.9 years. None of the girls showed precocious sexual development by the day of examination.

Impaired pancreatic growth, beta cell mass, and beta cell function in E2F1 (-/- )mice.

We evaluated the effects of E2F1 on glucose homeostasis using E2F1(-/-) mice. E2F1(-/-) mice show an overall reduction in pancreatic size as the result of impaired postnatal pancreatic growth. Furthermore, these animals have dysfunctional beta cells, linked to impaired PDX-1 activity. Because of the disproportionate small pancreas and dysfunctional islets, E2F1(-/-) mice secrete insufficient amounts of insulin in response to a glucose load, resulting in glucose intolerance. Despite this glucose intolerance, E2F1(-/-) mice do not develop overt diabetes mellitus because they have insulin hypersensitivity, which is secondary to a diminished adipose tissue mass and altered adipocytokine levels, which compensates for the defect in insulin secretion. These data demonstrate that factors controlling cell proliferation, such as E2F1, determine pancreatic growth and function, subsequently affecting metabolic homeostasis.

Impaired pancreatic growth, β cell mass, and β cell function in E2F1 –/– mice

We evaluated the effects of E2F1 on glucose homeostasis using E2F1–/– mice. E2F1–/– mice show an overall reduction in pancreatic size as the result of impaired postnatal pancreatic growth. Furthermore, these animals have dysfunctional β cells, linked to impaired PDX-1 activity. Because of the disproportionate small pancreas and dysfunctional islets, E2F1–/– mice secrete insufficient amounts of insulin in response to a glucose load, resulting in glucose intolerance. Despite this glucose intolerance, E2F1–/– mice do not develop overt diabetes mellitus because they have insulin hypersensitivity, which is secondary to a diminished adipose tissue mass and altered adipocytokine levels, which compensates for the defect in insulin secretion. These data demonstrate that factors controlling cell proliferation, such as E2F1, determine pancreatic growth and function, subsequently affecting metabolic homeostasis.

The Effects of &lt;I&gt;In Utero&lt;/I&gt; and Lactational Exposure to Chloroform on Postnatal Growth and Glucose Tolerance in Male Wistar Rats

Water chlorination results in the formation of trihalomethanes (THMs) including chloroform. In human stud-ies, fetal growth restriction has been associated with exposure to THMs during pregnancy and impaired fetal growth has been associated with an increased risk of type 2 diabetes. Therefore, the objective of this study was to determine the effect of in utero and lactational exposure to chloroform on birthweight and postnatal indicators of type 2 diabetes. Female Wistar rats were given chloroform (0 microg/L, 75 microg/L) in their drinking water for 2 wk prior to mating until parturition (in utero exposure only) or until weaning (in utero+lactational exposure). At postnatal d 1 (PND1) pups of dams exposed to chloroform had significantly higher serum glucose levels and lower insulin levels, but this effect was not due to b<FONT "Optima">-cell depletion in the neonatal pancreas. Glucose homeostasis in response to a glucose challenge was not changed by chloroform treatment. Chloroform exposure did not affect birthweight; however, offspring of dams exposed to chloroform had significantly impaired postnatal growth. Although fetal and neonatal exposure to chloroform did not elicit physiological changes associated with the onset of type 2 diabetes, there were physiological changes resulting in impaired postnatal growth.

Two-year outcome of infants weighing 600 grams or less at birth and born 1994 through 1998

Objective To assess the neurologic and developmental outcome at 2 years of age in preterm infants with birth weights 600 g or lower. Methods We conducted a retrospective review from January 1994 through December 1998 for placental histopathology, maternal factors, neonatal intensive care unit course, growth, neurologic/special sense status, and development at 2 years of age corrected for prematurity. Results Of the 104 neonates weighing 600 g or less, 24 survived to nursery discharge (23%). Two infants died of chronic lung disease after discharge, and 21 of the remaining 22 infants (95%) returned for follow-up. Placental pathology was available for 21 (95%); acute inflammation was present in 67%, and other abnormalities occurred in 76%. Mean birth weight was 537 (430–600) g, and mean gestational age was 24 (22–27) weeks. At birth, 55% were below the tenth percentile for birth weight. At nursery discharge and 2 years of age, 94% were below the tenth percentile for weight, length, and head circumference. Nineteen of 21 (90%) infants were abnormal on neurodevelopmental follow-up. Major problems were cerebral palsy, blindness, gastrostomies, and ventriculoperitoneal shunts. Conclusion Abnormal placental histology was present in all but one infant, suggesting fetal injury before birth. Only eight of 20 infants with chorioamnionitis were diagnosed clinically, and all infants had a complicated course. We found a high incidence of intrauterine growth restriction and an almost universal pattern of impaired postnatal growth with extremely poor neurodevelopmental outcome at 2 years of age.

Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects.

The subtilisin-like proprotein convertases PC1/3 (SPC3) and PC2 (SPC2) are believed to be the major endoproteolytic processing enzymes of the regulated secretory pathway. They are expressed together or separately in neuroendocrine cells throughout the brain and dispersed endocrine system in both vertebrates and invertebrates. Disruption of the gene-encoding mouse PC1/3 has now been accomplished and results in a syndrome of severe postnatal growth impairment and multiple defects in processing many hormone precursors, including hypothalamic growth hormone-releasing hormone (GHRH), pituitary proopiomelanocortin to adrenocorticotropic hormone, islet proinsulin to insulin and intestinal proglucagon to glucagon-like peptide-1 and -2. Mice lacking PC1/3 are normal at birth, but fail to grow normally and are about 60% of normal size at 10 weeks. They lack mature GHRH, have low pituitary growth hormone (GH) and hepatic insulin-like growth factor-1 mRNA levels and resemble phenotypically the "little" mouse (Gaylinn, B. D., Dealmeida, V. I., Lyons, C. E., Jr., Wu, K. C., Mayo, K. E. & Thorner, M. O. (1999) Endocrinology 140, 5066-5074) that has a mutant GHRH receptor. Despite a severe defect in pituitary proopiomelanocortin processing to mature adrenocorticotropic hormone, blood corticosterone levels are essentially normal. There is marked hyperproinsulinemia but without impairment of glucose tolerance. In contrast, PC2-null mice lack mature glucagon and are chronically hypoglycemic (Furuta, M., Yano, H., Zhou, A., Rouille, Y., Holst, J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H. & Steiner, D. (1997) Proc. Natl. Acad. Sci. USA 94, 6646-6651). The PC1/3-null mice differ from a human subject reported with compound heterozygosity for defects in this gene, who was of normal stature but markedly obese from early life. The PC1/3-null mice are not obese. The basis for these phenotypic differences is an interesting topic for further study. These findings prove the importance of PC1/3 as a key neuroendocrine convertase.

IGF-I, IGF Binding Protein (IGFBP)-3, Phosphoisoforms of IGFBP-1, and Postnatal Growth in Very Low Birth Weight Infants

Impaired postnatal growth in very low birth weight (VLBW, <1500 g) infants is per se a major clinical challenge and may also serve as a model in studying the mechanisms of growth retardation in general. This study was undertaken to characterize the role of IGFs and their binding proteins (IGFBPs), key regulators of fetal and infant growth, during the postnatal period in VLBW infants. Forty-eight VLBW infants (gestational age 27.6 ± 2.2 wk, birth weight 923 ± 257 g) were studied. Blood samples were drawn at 1, 2, 4, and 8 wk of age for measurements of IGF-I, IGFBP-1 (lesser phosphorylated, lpIGFBP-1, and highly phosphorylated, hpIGFBP-1), IGFBP-3, and insulin, simultaneous growth velocities being assessed by a rigorous protocol of repeated, frequent lower leg length and body weight measurements. All regression analyses were adjusted for postnatal age and repeated measurements. Lower leg growth velocity showed a positive correlation with IGF-I (P = 0.01) and IGFBP-3 (P = 0.03), and weight growth velocity with IGFBP-3 (P = 0.057) and with lpIGFBP-1/hpIGFBP-1 ratio (P = 0.01). Moreover, concurrent glucocorticoid dose showed a negative correlation with both IGFBP-1 isoforms, observable, however, only in samples with high (>10 U/liter) insulin (lpIGFBP-1, P = 0.02; hpIGFBP-1, P = 0.007). In backward multiple regression analysis, the factor remaining significantly associated with lower leg growth velocity (R2 = 0.63) was IGF-I, and factors associated with weight growth velocity (R2 = 0.81) were IGFBP-3 and the lpIGFBP-1/hpIGFBP-1 ratio. In conclusion, circulating IGF-I and IGFBP-3, and the lpIGFBP-1/hpIGFBP-1 ratio, reflect short-term growth velocity in VLBW infants. lpIGFBP-1 isoforms, abundant in the circulation of these infants, may thus also have properties that are at least less inhibitory, if not promoting, on the growth-stimulating action of IGF-I. Finally, the regulation of IGFBP-1 by glucocorticoids may be divergent in situations with a high or low insulin concentration.

IGF-I, IGF binding protein (IGFBP)-3, phosphoisoforms of IGFBP-1, and postnatal growth in very low birth weight infants.

Impaired postnatal growth in very low birth weight (VLBW, <1500 g) infants is per se a major clinical challenge and may also serve as a model in studying the mechanisms of growth retardation in general. This study was undertaken to characterize the role of IGFs and their binding proteins (IGFBPs), key regulators of fetal and infant growth, during the postnatal period in VLBW infants. Forty-eight VLBW infants (gestational age 27.6 +/- 2.2 wk, birth weight 923 +/- 257 g) were studied. Blood samples were drawn at 1, 2, 4, and 8 wk of age for measurements of IGF-I, IGFBP-1 (lesser phosphorylated, lpIGFBP-1, and highly phosphorylated, hpIGFBP-1), IGFBP-3, and insulin, simultaneous growth velocities being assessed by a rigorous protocol of repeated, frequent lower leg length and body weight measurements. All regression analyses were adjusted for postnatal age and repeated measurements. Lower leg growth velocity showed a positive correlation with IGF-I (P = 0.01) and IGFBP-3 (P = 0.03), and weight growth velocity with IGFBP-3 (P = 0.057) and with lpIGFBP-1/hpIGFBP-1 ratio (P = 0.01). Moreover, concurrent glucocorticoid dose showed a negative correlation with both IGFBP-1 isoforms, observable, however, only in samples with high (>10 U/liter) insulin (lpIGFBP-1, P = 0.02; hpIGFBP-1, P = 0.007). In backward multiple regression analysis, the factor remaining significantly associated with lower leg growth velocity (R(2) = 0.63) was IGF-I, and factors associated with weight growth velocity (R(2) = 0.81) were IGFBP-3 and the lpIGFBP-1/hpIGFBP-1 ratio. In conclusion, circulating IGF-I and IGFBP-3, and the lpIGFBP-1/hpIGFBP-1 ratio, reflect short-term growth velocity in VLBW infants. lpIGFBP-1 isoforms, abundant in the circulation of these infants, may thus also have properties that are at least less inhibitory, if not promoting, on the growth-stimulating action of IGF-I. Finally, the regulation of IGFBP-1 by glucocorticoids may be divergent in situations with a high or low insulin concentration.

Postnatal cystic germinolysis and neonatal chronic lung disease: evaluation of risk factors and neurodevelopmental outcome

Late neonatal onset of subependymal germinolysis in the caudothalamic groove has been associated with chronic lung disease. This clinical study had two objectives: (i) to clarify the link between chronic lung disease and germinolysis; and (ii) to evaluate the impact of germinolysis on neuromotor development of patients with chronic lung disease. Twenty‐four patients with chronic lung disease and germinolysis were compared to 24 patients, matched for gestational age, with chronic lung disease but without germinolysis. There was no difference in the occurrence of perinatal risk factors for impaired cerebral development (small for gestational age at birth, impaired postnatal growth, postnatal steroid treatment, duration of mechanical ventilation) or in the presence of clinical markers potentially related to cerebral ischaemia (need for treatment of hypotension or poor perfusion, seizures, oliguria, hypocapnia). Both groups showed a high incidence of clinically significant developmental delay (mean Bayley Development Index of 72 ± 23 [SD] in both groups), regardless of the presence or absence of germinolysis. Conclusions: We were unable to clarify the link between chronic lung disease and germinolysis, and it seems that germinolysis has no major impact on neurodevelopmental outcome of patients with chronic lung disease.

Postnatal cystic germinolysis and neonatal chronic lung disease: evaluation of risk factors and neurodevelopmental outcome

Late neonatal onset of subependymal germinolysis in the caudothalamic groove has been associated with chronic lung disease. This clinical study had two objectives: (i) to clarify the link between chronic lung disease and germinolysis; and (ii) to evaluate the impact of germinolysis on neuromotor development of patients with chronic lung disease. Twenty-four patients with chronic lung disease and germinolysis were compared to 24 patients, matched for gestational age, with chronic lung disease but without germinolysis. There was no difference in the occurrence of perinatal risk factors for impaired cerebral development (small for gestational age at birth, impaired postnatal growth, postnatal steroid treatment, duration of mechanical ventilation) or in the presence of clinical markers potentially related to cerebral ischaemia (need for treatment of hypotension or poor perfusion, seizures, oliguria, hypocapnia). Both groups showed a high incidence of clinically significant developmental delay (mean Bayley Development Index of 72+/-23 [SD] in both groups), regardless of the presence or absence of germinolysis. We were unable to clarify the link between chronic lung disease and germinolysis, and it seems that germinolysis has no major impact on neurodevelopmental outcome of patients with chronic lung disease.

Relation between Postnatal Physical Growth and Mental Development in Small for Gestational Age Infants

In 80 small for gestational age (SGA) low birth weight infants (birth weight less than 2, 000 g), the relation between mental development and postnatal physical growth was investigated. At the corrected age of 24 months, infants were classified into two groups by the Enjoji Developmental Screening Test: one with normal development and the other with mental delay. There were 55 infants with normal development and 25 with mental delay. Both groups were compared in birth condition, morbidity in the neonatal period and postnatal physical growth. There was a significant relation between mental development and postnatal growth of height, but not with growth at birth, neonatal morbidity or other measurements. These results suggest that SGA infants with impaired postnatal height growth may be at increased risk for mental delay.

Effects of zinc toxicity on thyroid function and histology in broiler chicks

Mechanisms of zinc (Zn) toxicity are incompletely understood and data regarding potential endocrine alterations in Zn toxicity are scarce. To examine mechanisms of Zn toxicity, day-old chicks were pair-fed diets containing 5280 ppm (Hz) or 73 ppm (CON) Zn. Impaired postnatal growth, independent of feed consumption, and multiple endocrinopathies were observed following short-term (1–2 weeks) exposure to the high Zn diet. Reduced levels of serum cholesterol, high-density lipoprotein cholesterol, and growth hormone were associated with HZ feeding. Depressed levels of circulating thyroid hormones and histological evidence that follicle area of thyroids from HZ birds was 63% less than CON indicated that impaired growth of HZ birds may be caused, in part, by reduced thyroidal function.