Postnatal Developmental Delay Research Articles

Interpretation of the first international consensus for Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is a genetic syndrome with severe neurodevelopmental disorders as the main manifestation. Its clinical manifestations included mental retardation, typical facial features, intrauterine and postnatal developmental delay, and deformity in multiple organs and systems, with an incidence rate of about 1/10000 to 1/30000. International CdLS Consensus Group was established in 2017 and issued the first international consensus on CdLS, i.e., "Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement", in July 2018. Being developed through a modified Delphi consensus process, this consensus provides guidance on the diagnosis and management of children with CdLS. This article gives an interpretation of this consensus, aiming to help clinicians with early identification, diagnosis, standard follow-up, and management of this disease.

Outcome of Pregnancy in Chromosomally Normal Foetus with Increased Nuchal Translucency

Objective: The aim of this study is to evaluate the outcome of pregnancy in prenatal and postnatal period of pregnancy complicated with thick nuchal translucency but normal karyotype. Methods: This is a retrospective study of 119 singleton pregnancies with increased NT (NT > 2.5mm) but a normal karyotype over a 3 year period. The records of ultrasound at 18-20 and 25-26 weeks’, antenatal and postnatal details were reviewed. The developmental and health outcomes of the surviving children were obtained through telephone conversation with the family. Adverse outcome such as miscarriages, termination of pregnancy, intrauterine death, structural anomalies and neurodevelopment delay were analysed. Results: Out of 119 foetuses with increased NT but normal karyotype, 11.8% of pregnancies ended with miscarriages, termination of pregnancy and intrauterine death. 89.9% foetuses were structurally normal. 12.9% presented with structural anomalies in the second-trimester ultrasound scan. 81.8% showed major malformations, out of which 44% consisted of heart defects. 1% of foetuses were syndromic and 1.9% had developmental delay. 96.8% of foetuses with NT equal to or greater than the 95th percentile (3.4mm) and 80% with NT equal to or greater than the 99 percentile (5.5mm) had a normal outcome. 50% of foetuses with thickened nuchal fold had a poor outcome. Postnatal follow-up was established for all infants and toddlers, and abnormalities were observed in 5.6% of them. Chances of having a live and healthy infant decreases with increased NT, corresponding to 80% for NT equal to or greater than 5.5mm. Conclusion: We have provided data that may help in the counselling of parents and increasing their confidence on a favourable pregnancy outcome. In cases with increased nuchal translucency but normal karyotype, the chances of normal pregnancy success rate is 89.9%. Parents can be reassured that thickened nuchal translucency with a normal karyotype and normal targeted ultrasound between 20-22 weeks gestation, the risk of adverse perinatal outcome and postnatal developmental delay is not increased in comparison with that of the general population. This seems to be the case for all degrees of increased nuchal translucency.

C14orf132 gene is possibly related to extremely low birth weight.

BackgroundDespite extensive research the genetic component of extremely low birth weight (ELBW) in newborns has remained obscure.ResultsThe aim of the case study was to identify candidate gene(s) causing ELBW in newborns and hypotrophy in infants. A family of four was studied: mother, father and two ELBW-phenotype children. Studies were made of the medical conditions of the second child at birth and post-partum - peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy and suspected metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate the genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 (chromosome 14 open reading frame 132) differentially expressed, with the level of the transcript significantly lower in the blood samples of the children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children.ConclusionWe demonstrated the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the pre- and early postnatal developmental delay through the altered gene expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0439-5) contains supplementary material, which is available to authorized users.

The Eyes Absent Proteins in Developmental and Pathological Angiogenesis

Management of neoangiogenesis remains a high-value therapeutic goal. A recently uncovered association between the DNA damage repair pathway and pathological angiogenesis could open previously unexplored possibilities for intervention. An attractive and novel target is the Eyes absent (EYA) tyrosine phosphatase, which plays a critical role in the repair versus apoptosis decision after DNA damage. This study examines the role of EYA in the postnatal development of the retinal vasculature and under conditions of ischemia-reperfusion encountered in proliferative retinopathies. We find that the ability of the EYA proteins to promote endothelial cell (EC) migration contributes to a delay in postnatal development of the retinal vasculature when Eya3 is deleted specifically in ECs. By using genetic and chemical biology tools, we show that EYA contributes to pathological angiogenesis in a model of oxygen-induced retinopathy. Both in vivo and in vitro, loss of EYA tyrosine phosphatase activity leads to defective assembly of γ-H2AX foci and thus to DNA damage repair in ECs under oxidative stress. These data reveal the potential utility of EYA tyrosine phosphatase inhibitors as therapeutic agents in inhibiting pathological neovascularization with a range of clinical applications.

Prenatal exposure to a novel antipsychotic quetiapine: Impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats

Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young–adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55mg, 80mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young–adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat.

Cornelia de Lange Sendromu:Ektromelia’lı Bir Olgu Sunumu

Cornelia de Lange syndrome (CDL), also known as Brachman de Lange syndrome, is characterised by distinct facial features, prenatal and postnatal developmental delay, and mental retardation. It has an incidence between 1/10000 and 1/60000. A four-month-old female patient with dysmorphic face and congenital malformations was diagnosed with CDL, and here presented because of the rare manifestations. Key-words: Cornelia de Lange syndrome, ectromelia, congenital malformations

Clinical, biochemical, and molecular studies in pyridoxine‐dependent epilepsy. Antisense therapy as possible new therapeutic option

Pyridoxine-dependent epilepsy seizure (PDE; OMIM 266100) is a disorder associated with severe seizures that can be controlled pharmacologically with pyridoxine. In the majority of patients with PDE, the disorder is caused by the deficient activity of the enzyme α-aminoadipic semialdehyde dehydrogenase (antiquitin protein), which is encoded by the ALDH7A1 gene. The aim of this work was the clinical, biochemical, and genetic analysis of 12 unrelated patients, mostly from Spain, in an attempt to provide further valuable data regarding the wide clinical, biochemical, and genetic spectrum of the disease. The disease was confirmed based on the presence of α-aminoadipic semialdehyde (α-AASA) in urine measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and pipecolic acid (PA) in plasma and/or cerebrospinal fluid (CSF) measured by high performance liquid chromatography (HPLC)/MS/MS and by sequencing analysis of messenger RNA (mRNA) and genomic DNA of ALDH7A1. Most of the patients had seizures in the neonatal period, but they responded to vitamin B6 administration. Three patients developed late-onset seizures, and most patients showed mild-to-moderate postnatal developmental delay. All patients had elevated PA and α-AASA levels, even those who had undergone pyridoxine treatment for several years. The clinical spectrum of our patients is not limited to seizures but many of them show associated neurologic dysfunctions such as muscle tone alterations, irritability, and psychomotor retardation. The mutational spectrum of the present patients included 12 mutations, five already reported (c.500A>G, c.919C>T, c.1429G>C c.1217_1218delAT, and c.1482-1G>T) and seven novel sequence changes (c.75C>T, c.319G>T, c.554_555delAA, c.757C>T, c.787+1G>T, c.1474T>C, c.1093-?_1620+?). Only one mutation, p.G477R (c.1429G>C), was recurrent; this was detected in four different alleles. Transcriptional profile analysis of one patient's lymphoblasts and ex vivo splicing analysis showed the silent nucleotide change c.75C>T to be a novel splicing mutation creating a new donor splice site inside exon 1. Antisense therapy of the aberrant mRNA splicing in a lymphoblast cell line harboring mutation c.75C>T was successful. The present results broaden our knowledge of PDE, provide information regarding the genetic background of PDE in Spain, afford data of use when making molecular-based prenatal diagnosis, and provide a cellular proof-of concept for antisense therapy application.

A boy with partial trisomy of chromosome 3q24–q28 from paternal balanced insertion and multiple congenital anomalies

Although many patients with duplication 3q syndrome have been described reports on duplication derivatives from an insertion are rare in the previous literature. Here we describe the genotype and phenotype of a 32-month-old boy with a partial trisomy of 3q24-q28. We carefully mapped the aberration with SNP-array analysis, and found a duplication region of 44 Mb. By conventional cytogenetic techniques including fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY) analysis, the patient was found to have inherited a derivative chromosome 6 from his father, which was contained a direct insertion from 3q24-28. The main clinical features of the patient included severe mental retardation, postnatal developmental delay, ventricular septal defect (VSD), and craniofacial anomalies including cleft palate, frontal bossing, hypertelorism, and a broad nasal bridge. The symptoms partially overlap with previously reported patients with duplication in the same region. Prenatal diagnosis for the fetus of this family was performed based on the results of genetic tests and ultrasonic evaluation.

Outcome of Fetuses With Cerebral Ventriculomegaly and Septum Pellucidum Leaflet Abnormalities

The objective of this study was to assess the outcomes of the prenatal diagnosis of septal leaflet abnormalities in fetuses referred for prenatal imaging with a finding of ventriculomegaly. This study is a retrospective review of fetuses with a diagnostic code of septal leaflet abnormalities from a larger prospective study. Four hundred twenty-five pregnant women with 433 fetuses referred for ventriculomegaly were imaged with ultrasound and MRI between July 1, 2003, and May 15, 2009. Four to six radiologists independently reviewed sonographic and MR images and recorded lateral ventricular diameters at the atrium and frontal horns, ventricular configuration, and the presence of ventriculomegaly and of other CNS abnormalities. Final prenatal ultrasound, MRI, and overall diagnoses were decided by consensus. Fetuses with a diagnostic code of septal leaflet abnormalities were identified, and birth outcome, autopsy findings, postnatal imaging, and postnatal follow-up examinations were obtained. The analysis of covariance, controlling for gestational age, was used to compare ventricular dimensions between fetuses with septal leaflet abnormalities and fetuses with isolated ventriculomegaly. Interrater agreement for the detection of septal leaflet abnormalities was assessed with kappa statistics. Interrater agreement and intrarater agreement for frontal horn measurements were assessed by variance components analysis. Twenty-three fetuses had septal leaflet abnormalities and 229 had isolated ventriculomegaly. Atrial and frontal horn diameters, adjusted for gestational age, were 77% and 98% larger, respectively, in fetuses with septal leaflet abnormalities than in fetuses with isolated ventriculomegaly (p < 0.0001). Before the consensus conference, agreement among ultrasound readers was moderate (κ = 0.54) and among MR readers, good (κ = 0.69). Additional CNS findings were seen on MRI in 12 of 23 fetuses (52%). Eleven pregnancies with septal leaflet abnormalities underwent termination and 12 progressed to livebirth; of the 12 livebirths, three neonates died. Neurodevelopmental follow-up was abnormal in all surviving children. A septal leaflet abnormality in the setting of ventriculomegaly is most frequently associated with other CNS abnormalities and is associated with postnatal developmental delay.

Two-component action of ATP on transmitter release from the motor nerve endings at the neuromuscular junction

s / Journal of Physiology Paris 99 (2006) 245–278 255 evoked synaptic responses, muscle twitch and tetanic tensions. In addition, complementary information was obtained by confocal laser scanning microscopical examination of the endplate region of the various transgenic muscles in order to determine the characteristics of muscle nicotinic ACh receptor clustering. The results obtained indicate that focally recorded miniature endplate currents (MEPC) exhibit a prolonged decay time in all transgenic mice examined with the exception of PRiMA / mutant muscles in which MEPCs were not affected. Complementary morphological examination revealed that there is an important remodeling and different clustering of muscle nicotinic ACh receptors at junctions lacking AChE activity in which MEPCs were prolonged. These results will be discussed in terms of physiological adaptation or compensation for the absence of AChE activity, and in relation to the expression of AChE and BChE at the neuromuscular junction. Supported by the AFM and by ACI # 0220530. doi:10.1016/j.jphysparis.2005.12.035 Camp, S., Zhang, L., Marquez, M., et al., 2004. In: Inestrosa, N.C., Campos, E.O. (Eds.), Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects. p. 43. Feng, G., Krejci, E., Molgo, J., Cunningham, J.M., Massoulie, J., Sanes, J.R., 1999. Genetic analysis of collagen Q: roles in acetylcholinesterase and butyrylcholinesterase assembly and in synaptic structure and function. J. Cell. Biol. 144, 1349–1360. Minic, J., Chatonnet, A., Krejci, E., Molgo, J., 2003. Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter release at normal and acetylcholinesterase knockout mouse neuromuscular junctions. Br. J. Pharmacol. 138, 177–187. Perrier, A.L., Massoulie, J., Krejci, E., 2002. PRiMA: the membrane anchor of acetylcholinesterase in the brain. Neuron 33 (2), 275–285. Xie, W., Stribley, J.A., Chatonnet, A., Wilder, P.J., Rizzino, A., McComb, R.D., Taylor, P., Hinriches, S.H., Lockridge, O., 2000. Postnatal developmental delay and supersensitivity to organophosphate in genetargeted mice lacking acetylcholinesterase. J. Pharmacol. Exp. Ther. 293, 896–902. The possible contribution of mast cells in the methylmercury-evoked effects Elizabeth E. Graevskaya Biophysical Department, Biological Faculty, Lomonosov Moscow State University, Vorobevy Gory, Moscow 119992, Russia E-mail address: graevsk@biophys.msu.ru Methylmercury (MeHg) is a well-established significant environmental neurotoxic agent, known as the cause of Minamata disease (IPCS, 1990). As it is known MeHg penetrates the blood-brain barrier to cause severe neurological symptoms in human beings and experimental animals, destructs neurons and glial cells, and disrupts neuronal migration. At the same time, increasing evidence indicates that neuroimmune interactions, including neuroinflammatory processes, may involve also mast cells. Mast cells and their transmitter content play a role in triggering an immune response in the brain. In our study we tried to define the possible contribution of mast cells in the development of methylmercury-evoked effects. As a model we used rat peritoneal mast cells, because it is easier to get the requisite amount of mast cells for measuring modifications of transmitter release. We investigated the effects of MeHg on mast cell degranulation induced by non-immunological stimuli (the selective inductor of histamine release): the compound 48/80 and the calcium ionophore A23187, both in vivo and in vitro. Eight, 12 and 15 days after administration of MeHg (10 mg/kg/day) we observed that the calcium ionophore A23187and 48/80-induced histamine release gradually decreased. Mast cells from rat exposed 24 or 72 h to a single dose of MeHg (20 mg/kg) showed a significant inhibition of the A23187-stimulated histamine secretion, but no change in the compound 48/ 80-stimulated release. In vitro incubation of peritoneal mast cells with MeHg alone (10 –10 6 M) did not induce mast cell degranulation, but modified the activation of mast cells by compound 48/80 and calcium ionophore A23187. We observed a facilitation of stimulated secretion by prior incubation with low dose of MeHg (10 8 M) and an inhibition at 10 6 M MeHg. These results show that MeHg treatment can modify mast cell function in vivo and in vitro and provide insight into the understanding what role this cell has in the pathogenesis of Minamata disease-connected disorders. doi:10.1016/j.jphysparis.2005.12.036 International Programm of Chemical Safety (IPCS), 1990. Environmental health criteria 101, methylmercury. World Health Organization, Geneva, p. 144. Effect of delta sleep inducing peptide on NMDA and GABA evoked ion currents in cortical, cerebellar and hippocampal

Acetylcholinesterase (AChE) gene modification in transgenic animals: Functional consequences of selected exon and regulatory region deletion

AChE is an alternatively spliced gene. Exons 2, 3 and 4 are invariantly spliced, and this sequence is responsible for catalytic function. The 3′ alternatively spliced exons, 5 and 6, are responsible for AChE disposition in tissue [J. Massoulie, The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11 (3) (2002) 130–143; Y. Li, S. Camp, P. Taylor, Tissue-specific expression and alternative mRNA processing of the mammalian acetylcholinesterase gene. J. Biol. Chem. 268 (8) (1993) 5790–5797]. The splice to exon 5 produces the GPI anchored form of AChE found in the hematopoietic system, whereas the splice to exon 6 produces a sequence that binds to the structural subunits PRiMA and ColQ, producing AChE expression in brain and muscle. A third alternative RNA species is present that is not spliced at the 3′ end; the intron 3′ of exon 4 is used as coding sequence and produces the read-through, unanchored form of AChE. In order to further understand the role of alternative splicing in the expression of the AChE gene, we have used homologous recombination in stem cells to produce gene specific deletions in mice. Alternatively and together exon 5 and exon 6 were deleted. A cassette containing the neomycin gene flanked by loxP sites was used to replace the exon(s) of interest. Tissue analysis of mice with exon 5 deleted and the neomycin cassette retained showed very low levels of AChE expression, far less than would have been anticipated. Only the read-through species of the enzyme was produced; clearly the inclusion of the selection cassette disrupted splicing of exon 4 to exon 6. The selection cassette was then deleted in exon 5, exon 6 and exons 5 + 6 deleted mice by breeding to Ella-cre transgenic mice. AChE expression in serum, brain and muscle has been analyzed. Another AChE gene targeted mouse strain involving a region in the first intron, found to be critical for AChE expression in muscle cells [S. Camp, L. Zhang, M. Marquez, B. delaTorre, P. Taylor, Knockout mice with deletions of alternatively spliced exons of Acetylcholinesterase, in: N.C. Inestrosa, E.O. Campus (Eds.), VII International Meeting on Cholinesterases, Pucon-Chile Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects. P. Universidad Catholica de Chile-FONDAP Biomedicina, 2004, pp. 43–48; R.Y.Y. Chan, C. Boudreau-Larivière, L.A. Angus, F. Mankal, B.J. Jasmin, An intronic enhancer containing an N-box motif is required for synapse- and tissue-specific expression of the acetylcholinesterase gene in skeletal muscle fibers. Proc. Natl. Acad. Sci. USA 96 (1999) 4627–4632], is also presented. The intronic region was floxed and then deleted by mating with Ella-cre transgenic mice. The deletion of this region produced a dramatic phenotype; a mouse with near normal AChE expression in brain and other CNS tissues, but no AChE expression in muscle. Phenotype and AChE tissue activities are compared with the total AChE knockout mouse [W. Xie, J.A. Chatonnet, P.J. Wilder, A. Rizzino, R.D. McComb, P. Taylor, S.H. Hinrichs, O. Lockridge, Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J. Pharmacol. Exp. Ther. 293 (3) (2000) 896–902].

Increased nuchal translucency with normal karyotype

Increased fetal nuchal translucency (NT) thickness between 11 and 14 weeks' gestation is a common phenotypic expression of chromosomal abnormalities, including trisomy 21. However, even in the absence of aneuploidy, nuchal thickening is clinically relevant because it is associated with an increase in adverse perinatal outcome caused by a variety of fetal malformations, dysplasias, deformations, dysruptions, and genetic syndromes. Once the presence of aneuploidy is ruled out, the risk of perinatal outcome dose not statistically increase until the nuchal translucency measurement reaches 3.5 mm or more (>99th percentile). This increase in risk occurs in an exponential fashion as the NT measurement increases. However, if the fetus survives until midgestation, and if a targeted ultrasound at 20 to 22 weeks fails to reveal any abnormalities, the risk of an adverse perinatal outcome and postnatal developmental delay is not statistically increased.

Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity

The allelic autosomal recessive lysosomal storage disorders Salla disease and infantile free sialic acid storage disease (ISSD) result from mutations in SLC17A5. This gene codes for sialin, a lysosomal membrane protein that transports the charged sugar, N-acetylneuraminic acid (sialic acid), out of lysosomes. ISSD has a severe phenotype with infantile onset, while the Finnish variant, Salla disease, has a milder phenotype with later onset. Both disorders cause developmental delay, and ISSD is generally fatal in early childhood. We describe a 30-month old non-Finnish, Caucasian child with global developmental delay of postnatal onset, language, and motor skills stagnant at a 3–4 month level, hypotonia, and mild but progressive coarsening of facial features. Urinary excretion of free sialic acid was elevated 4.5 times above control. EM of a skin biopsy revealed enlarged secondary lysosomes consistent with oligosaccharide storage. Free sialic acid in fibroblasts was 3.8 ± 0.9 nmol/mg protein (concurrent normal controls, 0.5 ± 0.1); differential centrifugation indicated a lysosomal location. Genomic analysis revealed compound heterozygosity for two new SLC17A5 mutations. This child’s clinical manifestations of a lysosomal free sialic acid storage disease are consistent with her sialin mutations and biochemical findings. The differential diagnosis of postnatal developmental delay should include free sialic acid storage disorders such as ISSD and Salla disease.

Postnatal developmental delay and chromosomal abnormalities.

Postnatal developmental delay and chromosomal abnormalities.

Importance of milk and diet on the ontogeny and adaptation of the intestine.

Importance of milk and diet on the ontogeny and adaptation of the intestine.

Malignancies diagnosed in pregnancy

The diagnosis of cancer is estimated to be associated with one in 1,000 pregnancies. Conversely, 0.8% of cancers are diagnosed in pregnant women. The lesions are more likely to present with advanced disease possibly as a result of greater difficulty in establishing diagnosis due to physiologic changes and symptoms of pregnancy, a hormonal milieu supportive of malignancy or immunosuppression. When compared stage for stage, the malignancies diagnosed in pregnancy are associated with the same prognosis as those identified in matched controls. The most common site diagnosed is cervix, followed by breast, skin (melanoma), lymph, ovary, colo/rectum, and thyroid. Presenting symptoms and evaluation are discussed. Treatment of these lesions has to be individualized based on the extent of the patient's disease, the gestational age of the fetus, and a consensus regarding the desire and advisability of continuing the gestation. Administration of chemotherapy during the first trimester may result in an increased risk of congenital anomalies depending on the type of agent and the timing in relationship to organogenesis. Chemotherapy is relatively safe following the completion of the process; more common side-effects have included growth retardation, postnatal developmental delay, and bone marrow suppression, with no detection of untoward effects in the majority of children. Fertility preservation following chemotherapy is related to the overall toxicity of the selected regimen and the age of the patient, with younger women experiencing a lower rate of ovarian failure. Radiation therapy is teratogenic, and its effect increases exponentially with doses above 0.1 Gy (=10 rads). Tumoricidal doses delivered to the pelvis will result in a spontaneous abortion. Other sites may be irradiated if the fetus can be effectively protected with shielding, which becomes more difficult as the pregnancy advances. Fertility should be unaffected if the ovaries are not in the irradiated field; fractionated doses in excess of 1,500 cGy or a single dose greater than 700 cGy will lead to ovarian failure. In conclusion, malignancies are rarely diagnosed in pregnancy, but present in more advanced stages of disease. The survival is comparable to matched controls. Treatment is highly individualized but can often be delivered safely during pregnancy. Awareness of the more common types of cancers presenting in pregnancy, their symptoms and diagnositic evaluation, as well as familiarity with possible treatments will allow the clinician caring for pregnant women to aid in earlier diagnosis and expedite referral for counseling and treatment.

Locomotor activity and postnatal development of rats after exposure to 2,3,7,8-TCDD during the late fetal and early postnatal period

Postnatal physical development and locomotor activity was studied in offspring of Wistar rats exposed to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) in the late fetal and early postnatal period. The dosing schedule used caused a slight delay in development, as evaluated by a reduced body weight gain during the 2 nd to 4 th week of the study. No significant differences in the locomotor activity between controls and TCDD-exposed offspring were detectable under our experimental conditions. The same holds true for the signs of physical development when the slight delay in postnatal development was taken into consideration.

The Effect of Protein-Calorie Malnutrition on the Developing Liver

The effects of protein-calorie malnutrition on bile salt metabolism and liver function were studied. Malnutrition was induced in rabbits by combining litters at 7 days of age (13-16 animals) and results compared to control litters (six-eight animals). At age 29-30 days biliary output from the common bile duct was measured directly for three 1-h periods: under basal conditions, and in response to intravenous infusion of exogenous glycodeoxycholic acid at 0.75 and 1.5 mumol/min/kg, respectively. The bile salt pool size was measured by isotope dilution. Final mean body weight and liver weight were significantly decreased in malnourished animals compared to controls. Liver weight/body weight was also less in the malnourished group. Total liver DNA and protein content, as well as the protein to DNA ratio, were less in the malnourished animals compared to controls. Bile flow and bile salt secretion were reduced in the malnourished group when calculated per kg body weight or per mg liver DNA. Bile salt-dependent flow did not differ significantly, but bile salt-independent flow was significantly less in malnourished animals. Bile salt pool size was decreased in the malnourished group. These findings indicate that malnutrition has a greater impact on liver weight than on total body weight in the preweaning period. In addition, malnutrition reduces bile flow, bile salt secretion, and bile salt pool size which, along with the decrease in bile salt-independent flow, may reflect either an impairment of hepatic uptake function or a delay in postnatal development.

Growth and development of mice offspring after irradiation in utero with 2,450-MHz microwaves.

Mice offspring irradiated in utero with 2,450-MHz radio-frequency (RF) radiation at 0 or 28 mW/cm2 (whole-body averaged specific absorption rate = 0 or 16.5 W/kg) for 100 minutes daily on days 6 through 17 of gestation were evaluated for maturation and development on days 1, 5, 10, 12, 15, and 17 of age. The tests used to determine differences in developmental age in the two treatment groups were body weight, urine concentrating ability, brain weight, tolerance to ouabain, and bone lengths. Fifteen sham-irradiated and 26 RF-irradiated litters, normalized to eight pups/litter, were used in this study. Mean body weight of the microwave-irradiated offspring were significantly (p = .0003) decreased only on day 1 of age. Brain weight on days 10, 12, and 17 were significantly lower in microwave-irradiated pups (p = .01). There were no significant differences in the two groups in urine concentrating ability on day 5, ouabain tolerance on day 15, or bone length on days 5, 10, 12, and 17. It is concluded that there is a persistent delay in postnatal development of the brain after RF irradiation with 16.5 W/kg during gestation.

Patterns of psycholinguistic development in the severely mentally retarded: a hypothesis.

Abstract We hypothesize that the loss of psycholinguistic skills in some cases of severe mental retardation caused by prenatal disruption closely approximates ontogenetic patterns of language acquisition and phylogenetic patterns of cognitive development. This hypothesis was tested on 131 trainable mental retardates divided into four etiological classes. The results support the hypothesis and show that certain patterns of loss occur only in mental retardation resulting from prenatal disruption and characterized by postnatal developmental delay and do not occur in postnatal environmentally caused retardation.