Low birth weight as an additional indication for chromosomal analysis

INTRODUCTION: Even though there are few epidemiological studies evaluating the birth weights of different groups of malformed babies with chromosomal abnormalities, it is widely known that infants with trisomy 18, and to a lesser degree those with trisomy 13 and other chromosomal alterations, have low birth weights. PATIENTS AND METHODS: In this study we present the analysis of the birth weights and gestational ages of a large sample of babies (23,155 malformed and a similar number of nonmalformed babies), separating the different groups of chromosomal anomalies and comparing the weight in the clinical groups of malformed infants. RESULTS: Most of the groups with chromosomal abnormalities present lower birth weights in comparison to the other groups. CONCLUSIONS: The results of our study support the conclusion that the relationship between chromosomal alterations and low birth weight is sufficiently important that such a low birth weight in children with minor or major anomalies should be considered as one more indication to perform chromosomal analysis.     

Minor physical anomalies in schizophrenic patients and their siblings

OBJECTIVE: The aim of this study was to assess the frequency and type of minor physical anomalies in schizophrenic patients and their normal siblings. METHOD: Sixty adult patients with schizophrenia, 21 siblings of these patients, and 75 normal comparison subjects were assessed through use of an extended scale consisting of the Waldrop scale and 23 other minor physical anomalies. RESULTS: Patients had significantly more minor physical anomalies than comparison subjects in all body areas tested and also more minor physical anomalies in total than their siblings. Hand, eye, and mouth minor physical anomalies best discriminated patients from comparison subjects. Siblings had significantly more minor physical anomalies than normal comparison subjects. Sixty percent of the patients and 38% of the siblings, but only 5% of the comparison subjects, had a higher rate of minor physical anomalies (i.e., six or more). With the exception of ear minor physical anomalies, no association was found between minor physical anomalies in the patient and sibling in the same family. CONCLUSIONS: Higher levels of minor physical anomalies (especially in the eye, mouth, and hand/foot regions) characterize both schizophrenic patients and their normal siblings, but there is little similarity in these anomalies between patients and siblings in the same family. Thus, one or more genetic or shared environmental factors may increase the risk for development of both minor physical anomalies and schizophrenia in these families at large. Minor physical anomalies associated with schizophrenia are frequently found in, but are clearly not limited to, the head or facial region. The Waldrop scale identifies minor physical anomalies strongly associated with schizophrenia. Nevertheless, assessment of the new items clearly indicates that many additional minor physical anomalies are found in schizophrenic patients.     

Basic assessment series: the adult pulmonary system

OBJECTIVE: The study was conducted to evaluate the spread of the minor physical anomalies (MPAs) in patients with schizophrenia and normal subjects, and the relevance of MPAs to sex, age of onset of the disease, birth order, and season of birth. METHODS: Forty two inpatients satisfying the DSM-IV criteria for schizophrenia and 36 normal controls were evaluated for MPAs using the Waldrop scale. Subjects with schizophreniform, schizoaffective and schizotypal personality disorders were excluded from the sample to prevent these from possible confounding of the results. RESULTS: The schizophrenic patients showed significantly more anomalies than the controls. In both male and female patients, there was a higher incidence of anomalies in the region of the head. Significantly higher scores for minor physical anomalies were associated with later position in the birth order. Gender differences were without statistical significance. No relationship was found between minor physical anomalies and age of onset of the disease and birth season. CONCLUSION: The results are consistent with the theory of disturbed craniofacial development in at least one subpopulation of schizophrenic patients and indicate the origins of the disturbance in the early embryonal period. The higher incidence of anomalies in the region of head reflects the complex processes in the morphogenesis of mouth, ears and eyes.     

A comparison of one-sided methods to identify significant individual outcomes in a multiple outcome setting: stepwise tests or global tests with closed testing

We compare two approaches to the identification of individual significant outcomes when a comparison of two groups involves multiple outcome variables. The approaches are all designed to control the familywise error rate (FWE) with any subset of the null hypothesis being true (in the strong sense). The first approach is initially to use a global test of the overall hypothesis that the groups are equivalent for all variables, followed by an application of the closed testing algorithm of Marcus, Peritz and Gabriel. The global tests considered here are ordinary least squares (OLS), generalized least squares (GLS), an approximation to a likelihood ratio test (ALR), and a new test based on an approximation to the most powerful similar test for simple alternatives. The second approach is that of stepwise testing, which tests the univariate hypotheses in a specific order with appropriate adjustment to the univariate p-values for multiplicity. The stepwise tests considered include both step-down and step-up tests of a general type, and likewise permutation tests that incorporate the dependence structure of the data. We illustrate the tests with two examples of birth outcomes: a comparison of cocaine-exposed new-borns to control new-borns on neurobehavioural and physical growth variables, and, in a separate study, a comparison of babies born to diabetic mothers and babies born to non-diabetic mothers on minor malformations. After describing the methods and analysing the birth outcome data, we use simulations on Gaussian data to provide guidelines for the use of these procedures in terms of power and computation.     

Modeling volatility using state space models

Although much research has focused on whether the physical demands of employment during pregnancy affect birth outcomes, this article argues that psychological demands should also be considered. Research published since 1980 is reviewed to examine how physical and psychological demands of employment are related to birth outcomes. Evidence for the effect of specific types of physical activities (e.g., lifting, standing) is equivocal, in part due to methodological limitations. However, studies combining several types of physical activities tend to find an association with more adverse birth outcomes. Too few pregnancy outcome studies have examined psychological demands in the workplace to make conclusions about birth outcomes, but the theoretical basis for further research is discussed. This article also argues that physical and psychological demands occur outside of the workplace and must therefore be considered with respect to responsibilities all women face throughout the day. An integrative model for studying these relationships is proposed.     

Management of craniofacial anomalies

Children with craniofacial anomalies comprise a diverse group of patients, with problems involving many organ systems. In the fairly recent past, no satisfactory treatment was available for many of these problems. Through the contributions of Tessier and many other innovators, however, multidisciplinary groups such as the Medical University of South Carolina's Craniofacial Team are now able to offer substantial improvement to many patients with congenital or acquired deformities of the craniofacial region. The best reconstruction for any given patient can be determined only after a careful analysis of the patient's problems and the patient's and family's wishes. Using this approach, we are able to help many patients significantly. As we treat today's patients, however, we must continue to critically assess our results and improve our methods, for only through this process will tomorrow's patients enjoy even better outcomes than today's.     

Skeletal and cardiac malformations with thrombocytopenia: a new syndrome?

We describe a female patient with multiple anomalies suggestive of a new syndrome. Manifestations include: VSD and ASD, mild developmental delay, conductive hearing loss, minor facial anomalies, thrombocytopenia, and radiological findings (including carpal fusion). Some of these manifestations may be present in the Keutel syndrome, IVIC syndrome, and the 10qter deletion syndrome. However, none of these syndromes can explain the spectrum of anomalies seen in our patient.     

Routine prenatal screening for congenital heart disease: what can be expected? A decision-analytic approach

OBJECTIVES: This study assessed the potential impact of fetal ultrasound screening on the number of newborns affected by cardiac anomalies. METHODS: A decision model was developed that included the prevalence and history of congenital heart disease, characteristics of ultrasound, risk of abortion, and attitude toward pregnancy termination. Probabilities were obtained with a literature survey; sensitivity analysis showed their influence on expected outcomes. RESULTS: Presently, screening programs may prevent the birth of approximately 1300 severely affected newborns per million second-trimester pregnancies. However, over 2000 terminations of pregnancy would be required, 750 of which would have ended in intrauterine death or spontaneous abortion. Further, 9900 false-positive screening results would occur, requiring referral. Only the sensitivity of routine screening and attitude toward termination of pregnancy appeared to influence the yield substantially. CONCLUSIONS: The impact of routine screening for congenital heart disease appeared relatively small. Further data may be required to fully assess the utility of prenatal screening.     

Developmental instability and cerebral lateralization

On the basis of prior studies of handedness, it was predicted that variations from modal asymmetry scores on cognitive tasks, in either direction from the mean, would be associated with an elevated incidence of classic markers of developmental instability (minor physical anomalies and fluctuating anatomic asymmetries). University students (N = 146) were administered 4 tasks that typically reveal functional asymmetries: the fused rhymed words dichotic listening task, the line bisection task, the chimeric faces task, and the cartoon faces task. A composite measure of developmental instability was computed from minor physical anomalies and fluctuating asymmetries. Participants with greater evidence of developmental instability had more atypical lateralization scores, deviating more from the sample mean, in either direction. Directional asymmetries were unrelated to developmental instability. These results suggest that developmental instability influences variation in the lateralization of cognitive skills as well as handedness.     

Children conceived by in vitro fertilisation after fresh embryo transfer

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.     

Prospective assessment of pregnancy outcomes after first-trimester exposure to fluconazole

OBJECTIVE: Our purpose was to study prospectively the pregnancy outcome after first-trimester exposure to fluconazole, an effective antifungal agent teratogenic in animals. STUDY DESIGN: We conducted a prospective cohort study of women who contacted three Italian teratogen information services. We compared the pregnancy outcomes of 226 women exposed to fluconazole with that of 452 women exposed to nonteratogenic agents, with use of logistic regression to control for potential confounders. RESULTS: Among the 226 pregnancies exposed to fluconazole there were 22 miscarriages, 1 stillbirth, and 7 infants with congenital anomalies. The prevalence of these outcomes and of neonatal growth parameters and the rate of neonatal complications were similar to those in the reference group. Women in the fluconazole group had a fivefold increased occurrence of induced abortions. CONCLUSIONS: First-trimester exposure to fluconazole does not appear to increase the prevalence of miscarriages, congenital anomalies, and low birth weight.     

Spectrum of ischemic heart disease and the role of biochemical markers

An exciting era exists as a result of the introduction of novel markers of myocardial damage. The prognostic implications of troponins, even in the setting of "minor myocardial damage," are potentially of immense value to patient care. We need to take the next step and assess the outcomes of interventions in these settings. Use of new markers at triage will probably allow for more efficient and safe disposition of patients in this setting. There are many advantages and disadvantages to the current markers and many unanswered questions. Only through well-designed large clinical trials will we be able to realize the true potential of these markers.     

CHARGE syndrome: report of 47 cases and review

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.     

Obscure encopresis, other incontinence, and their treatments.

Examines research on psychological aspects of bowel incontinence as well as T. Ferguson's (1979) review of diagnostic and treatment approaches to encopresis with respect to the validity of psychogenesis. It is maintained that psychologists should make their treatments consonant with physical and psychological conditions present in the patient (e.g., the eliminatory tract and patient's motivation). Outlined are treatment procedures and a case report of a 13-yr-old male with multiple birth defects as an illustrative example. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parental handedness and relative hand skill: A test of the developmental instability hypothesis.

In previous studies (e.g, R. A. Yeo et al; see record 1993-40422-001), both left-handers and extreme right-handers showed evidence of increased developmental instability, as indexed by minor physical anomalies and by specific fluctuating anatomic asymmetries. Thus, developmental instability may be an important factor affecting handedness. In the present study, a specific prediction of the developmental instability model of handedness, one that distinguishes it from the single-gene models of M. Annett (1985) and I. C. McManus (see record 1986-21280-001), was tested among 225 undergraduates. The model suggests that the degree of deviation from modal handedness, rather than direction of handedness, is heritable. Thus, it was hypothesized that extreme right-handers as well as left-handers have an elevated proportion of left-handed parents. Results supported this hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nucleotide sequence and genetic analysis of the leader region of Canadian, American and European equine arteritis virus isolates

We present the first report of chromosomal rearrangement involving chromosomes 4, 10 and 12. The proband was a 42-year-old woman with severe mental retardation and multiple congenital anomalies. The most striking physical anomalies were upper limb contractures resulting in distal arthrogryposis. As upper limb flexion contractures have been previously reported in individuals with partial distal 10q deletion, this sign should be considered as part of the clinical manifestations of 10q25-->qter monosomy.     

Functional equivalence of native light-sensitive channels in the Drosophila trp301 mutant and TRPL cation channels expressed in a stably transfected Drosophila cell line

As we have pointed out in this article, a health care study should have a well-defined intent that is matched to the study type, population of interest, and outcome. Care must be taken to collect samples in a meaningful way, so that results can be generalized to larger populations. Outcomes must be selected carefully to ensure that they will be sensitive to the types of care being considered, and only a few main outcomes should be selected so as to preserve the level of statistical significance of the research results. Sample sizes should be sufficient to detect an effect of reasonable size, after accounting for attrition in longitudinal studies and rates of occurrence with dichotomous outcomes. If the study purpose is to compare multiple institutions or health care providers, statistical adjustments for case mix will generally be required. Outcome research is an expanding area of development for rheumatology care and for medical care in general. It offers the promise of the use of administrative data bases to answer questions that are important both to arthritis researchers and to consumers of rheumatology care. As with all areas of clinical research, we must maintain appropriate levels of statistical rigor to protect the integrity of the results. Inadequate attention to the design and analysis of data can compromise research results before a study even gets started, and health care research studies have as many potential statistical pitfalls as other types of clinical research.     

The impact of routine obstetric ultrasonographic screening in a low-risk population

OBJECTIVES: Our goal was to develop a framework for evaluating the current controversy regarding routine obstetric ultrasonography in a population of low-risk pregnancies. STUDY DESIGN: A retrospective chart review was performed for all low-risk pregnancies from a single obstetric practice during 1990 to 1994, to determine the accuracy of screening ultrasonography for fetal anomalies. All patients received a routine ultrasonographic examination at 18 to 20 weeks' gestation. Neonatal records for all patients were evaluated for the presence of both major and minor anomalies. The data were analyzed with attention to the classification of anomalies (all anomalies vs major anomalies, detectable vs nondetectable). RESULTS: A total of 860 fetuses in 854 pregnancies were evaluated. Anomalies were present in 5.35% (46/860); these were major anomalies in 1.16% (10/860) and minor anomalies in 4.19% (36/860). The sensitivity, specificity, and positive and negative predictive values for the diagnosis of all anomalies were 8.7%, 99.9%, 80%, and 95.7%, respectively. However, if only major anomalies detectable by ultrasonography are included, these values become 75%, 100%, 100%, and 99.9%, respectively. There was one false-positive diagnosis not affecting outcome, a small ventriculoseptal cardiac defect. Postnatal ascertainment of anomalies was excellent, as determined by an incidence of ventriculoseptal defects of 1 in 120. CONCLUSION: Distinguishing between major and minor anomalies and between ultrasonographically detectable versus nondetectable anomalies is essential in the evaluation of the diagnostic accuracy of screening ultrasonography. Any comparisons of studies examining the effectiveness of prenatal screening for congenital anomalies with ultrasonography should use the same outcome: major anomalies identifiable by ultrasonography.     

A record-linkage study on risk factors for cause-specific infant mortality

Infant death certificates were linked with birth certificates for infants born to residents of Tohoku, Tokai and Kyushu regions in 1989 (n = 409, 679, or about one-third of all births in Japan), to examine the effects of variables, as reported on birth certificates, on cause-specific infant mortality. "Certain conditions originating in the perinatal period" and "congenital anomalies" accounted for nearly 90 percent of neonatal deaths, while "congenital anomalies", "injuries and poisoning" and "sudden infant death" were responsible for about 65 percent of postneonatal deaths. Mortality rates for almost all causes of infant deaths, except injuries and poisonings, increased as birth weight decreased not only in the neonatal period but also in the postneonatal period. This suggests that low birth weight places some infants at higher risk of death, and conditions that lead to low birth weight independently contribute to the risk of infant death. Cox's proportional hazards linear model was used to assess the effects of variables on infant mortalities by causes of death. An extremely strong birth weight effect was noted for "certain conditions originating in the perinatal period" and "congenital anomalies". Being a male infant and late order of birth in multiparity were other risk factors for deaths from "congenital anomalies", while being a male infant, resident of Tohoku region and maternal stillbirth experience related to deaths from "certain conditions originating in the perinatal period". Elevated risks of sudden infant death syndrome (SIDS), of which mortality rate in Japan was considerably lower than those in most developed Western countries, i.e. 0.23 per 1,000 live births in 1989, were associated with low birth weight, being a male infant, low maternal age, late order of birth in multiparity and illegitimacy. Low maternal age, late order of birth in multiparity and illegitimacy, also, related significantly to increased risk of infant deaths for "injuries and poisoning". These results suggest the independent contributions of socioeconomic factors to infant mortality, especially postneonatal mortality, from SIDS, "injuries and poisonings".     

Application of a colorimetric DNA-DNA hybridization method for identification of Aeromonas genomic species, isolated from diarrheal stools

In this report we describe a male patient with the interesting combination of a large congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media. Follow-up data from birth up to the age of 18 years revealed positive evolution with low to normal intelligence. The findings in the present patient, i.e. an Adams-Oliver syndrome associated with a severe neurological deficit, are best explained as resulting from interruption of the early embryonic blood supply.