Search PubMed⌕ Search

Biomedical subjects

S K Clarren

Publications and source records attributed to S K Clarren.

At least 37 records · Page 2Linked to original sources
PubMed1992

Cognitive and behavioral deficits in nonhuman primates associated with very early embryonic binge exposures to ethanol.

This study was undertaken to evaluate teratogenesis associated with early weekly ethanol exposure followed by later gestational abstinence. Ethanol, 1.8 gm/kg, was orally administered weekly to gravid nonhuman primates (Macaca nemestrina) for the first 3, 6, or the entire 24 weeks of pregnancy. Control animals received weekly sucrose solution as did the 3- and 6-week cohort animals in subsequent weeks. Thirty-five viable infants were assessed for growth, malformations, and behavioral and cognitive dysfunction. Animals in the 6-week and 24-week cohorts were uniformly abnormal in behavior and inconsistently abnormal in physical development relative to the control animals. Animals in the 3-week cohort were equivocally normal. These results demonstrate ethanol's capacity to produce behavioral teratogenesis (brain dysfunction) in isolation from physical anomalies in the rest of the body. The results strongly suggest that binge drinking in the first 6 to 8 weeks of pregnancy (a period when women may not know that they are pregnant), followed by later gestational abstinence, is as dangerous to the fetus as exposure throughout gestation.

Abnormalities, Drug-Induced↗
PubMed1992

Analysis of facial shape in children gestationally exposed to marijuana, alcohol, and/or cocaine.

The association between fetal marijuana and/or alcohol exposure and facial features resembling fetal alcohol syndrome was investigated in a sample of 80 children. Standardized lateral and frontal facial photographs were taken of 40 children, 5 to 7 years of age, whose mothers reported frequent use of marijuana during the first trimester of pregnancy and 40 children whose mothers reported no use of marijuana during pregnancy. The marijuana-exposed and unexposed children were group-matched on alcohol exposure prior to and during pregnancy, sex, race, and age at the time of assessment. The photographs were assessed clinically by a study staff dysmorphologist and morphometrically by computerized landmark analysis. Fetal alcohol syndrome-like facial features were not associated with prenatal marijuana exposure in this study sample. No consistent patterns of facial features were identified among the marijuana-exposed group. Maternal consumption of two or more ounces of alcohol per day, on average, in early gestation was found to be associated with fetal alcohol syndrome-like facial features identified both clinically and morphometrically. Cocaine use reported by 13 of the 80 women was independently associated with mild facial dysmorphic features of hypertelorism and midfacial flattening. The results demonstrate the usefulness of this diagnostic technique for quantifying anomalies apparently unique to fetal alcohol syndrome and for targeting clusters of anomalies in new conditions for future evaluation.

Alcohol Drinking↗
PubMed1991

Extending the Pallister-Hall syndrome to include other central nervous system malformations.

Hall-Pallister syndrome is defined by specific facial anomalies, post axial polydactyly, imperforate anus, and brain anomalies including a rare diencephalic mass, hypothalamic hamartoblastoma. In this article, two patients are described with the usual features of Hall-Pallister syndrome, including diencephalic anomalies, but without hamartoblastomas. These patients may suggest an appropriate extension of the definition of the Hall-Pallister syndrome.

Abnormalities, Multiple↗
PubMed1991

Fetal alcohol syndrome in adolescents and adults.

Fetal alcohol syndrome is a specific recognizable pattern of malformation. Manifestations in 61 adolescents and adults suffering from alcohol teratogenesis are presented. After puberty, the faces of patients with fetal alcohol syndrome or fetal alcohol effects were not as distinctive. Patients tended to remain short and microcephalic, although their weight was somewhat closer to the mean. The average IQ was 68, but the range of IQ scores widely varied. Average academic functioning was at the second- to fourth-grade levels, with arithmetic deficits most characteristic. Maladaptive behaviors such as poor judgment, distractibility, and difficulty perceiving social cues were common. Family environments were remarkably unstable. Fetal alcohol syndrome is not just a childhood disorder; there is a predictable long-term progression of the disorder into adulthood, in which maladaptive behaviors present the greatest challenge to management.

Adaptation, Psychological↗
PubMed1991

Holoprosencephaly in a fetal macaque (Macaca nemestrina) following weekly exposure to ethanol.

Previous studies in rodents have indicated that the facial changes of fetal alcohol syndrome (FAS) closely resemble those of a mild form of holoprosencephaly. In order to examine this relationship in non-human primates, we evaluated a 133-day gestation macaque (Macaca nemestrina) with holoprosencephaly, median cleft lip and palate, and encephalocele. The mother had been given ethanol once per week (1.8 g/kg body weight) from weeks 2 to 19 postconception. Diagnosis of holoprosencephaly was made following ultrasound evaluation for polyhydramnios and delivery of the female fetus by caesarean section. Another fetus of identical age was delivered by caesarean section for use as a control. Both fetuses were studied by anthropometric, gross, radiographic, and histologic techniques. In the fetus exposed to alcohol, no extracranial anomalies were identified and the karyotype was normal. The brain was micrencephalic, with absent olfactory bulbs, tracts, optic nerves and chiasma, fused frontal lobes, and a single, dilated lateral ventricle; a parietooccipital encephalocele consisted of thin, dysplastic cortex bordering the ventricle; the cerebellum was dysplastic and superiorly displaced. Within the craniofacial complex, anophthalmia was bilateral; premaxillary components were absent, palatal shelves separate, the maxillae closeset, and the ethmoid bone small and deformed. Most of these defects are similar to those encountered in humans with holoprosencephaly and support the hypothesis of shared etiologic and pathogenetic relations between the facial anomalies of fetal alcohol syndrome and holoprosencephaly.

Animals↗
PubMed1991

Nasal dermoid sinus cysts: association with intracranial extension and multiple malformations.

Nasal dermoid and sinus cysts (NDSC) are uncommon congenital anomalies that may have intracranial extension and can be associated with other anomalies. We identified 22 patients in a retrospective review of cases diagnosed with NDSC at our institution over the past 10 years. Nine (41 percent) had associated anomalies and ten (45 percent) had intracranial extension of the sinus. In half of the patients with intracranial extension, the sinus transversed either the cribriform plate or foramen cecum and attached to the dura; in the other half, the sinus extended to cysts within the falx or other brain structures. Of the patients with multiple anomalies, six (67 percent) had intracranial extension. Presurgical complications occurred in a total of eight patients (36 percent): two had meningitis, two had osteomyelitis, four had periorbital-nasal cellulitis, three had nasal abscess, and four had nose anomalies requiring rhinoplasty.

Abnormalities, Multiple↗
PubMed1990

Partial deletion of the long arm of chromosome 11 [del(11)(q23.3----qter)] with abnormal white matter.

A patient with partial deletion of the long arm of chromosome 11[del(11)(q23.3----qter)] had macrocephalic trigonocephaly, growth and mental retardation, congenital heart defect, and characteristic facial appearance familiar to that of 33 other reported patients with this deletion. Computed tomography (CT) and magnetic resonance imaging of this infant's brain demonstrated abnormality of the supratentorial white matter. This may represent either deficiency or delay in myelination or possibly a demyelination process. No abnormalities in white matter were described in seven of 33 previously reported patients whose brains were examined by ultrasound, CT, or autopsy.

Abnormalities, Multiple↗
PubMed1990

Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation.

Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3 or 4.1 gm/kg from the 5th week. Mean maternal peak plasma ethanol concentrations (MPPEC's) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. Thirty-three live born infants were assessed for abnormalities of physical and behavioral development. Ocular pathology, neuropathologic and neurochemical assessements were done on 31 animals at 6 months postnatal age. Microphthalmia was noted in three of the 26 animals exposed to ethanol. Retinal ganglion cell loss was significantly associated with intra-uterine ethanol exposure. Microphthalmia and retinal ganglion cell loss was observed in both the delayed and full-gestational exposed animals. No structural anomalies were found in the brains via gross inspection or light microscopy. Chemical abnormalities in the striatal nuclei were identified. Striatal dopamine concentrations increased with increasing MPPEC exposure (0-249 mg/dl) among animals exposed weekly to ethanol throughout gestation. Striatal dopamine concentrations decreased with increasing MPPEC exposure (260-540 mg/dl) among animals whose weekly exposure to ethanol was delayed until the 5th week of gestation. The same pattern of association was also noted between MPPEC and ultrastructural alterations in the caudate nucleus. The extent of ultrastructural alterations increased with increasing MPPEC among the full-gestational exposed animals and decreased with increasing MPPEC among the delayed-dose animals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Maternal alcohol use during breast-feeding and infant mental and motor development at one year.

The detrimental effects of maternal drinking during pregnancy on fetal health have been documented. The consequences for infants of maternal drinking during breast-feeding are unknown, but research in animals suggests that the infant could be affected by exposure to alcohol through the mother's milk. In a study of 400 infants born to members of a health maintenance organization, we investigated the relation of the mother's use of alcohol during breast-feeding to the infant's development at one year of age. Mental development, as measured by the Bayley Mental Development Index (MDI), was unrelated to maternal drinking during breast-feeding. However, motor development, as measured by the Psychomotor Development Index (PDI), was significantly lower in infants exposed regularly to alcohol in breast milk (after alcohol exposure during gestation was controlled for), with a dose-response relation (P for linear trend, 0.006). The infants of breast-feeding mothers who had at least one drink daily had a mean PDI score of 98, whereas the infants exposed to less alcohol in breast milk had a mean PDI score of 103 (95 percent confidence interval for the difference of the two means, 1.2 to 9.8). The effect was more pronounced when mothers who supplemented breast-feeding with formula were excluded from the analysis. The association persisted even after we controlled for more than 100 potentially confounding variables, including smoking and other drug use during pregnancy and in the postpartum period. We conclude that ethanol ingested through breast milk has a slight but significant detrimental effect on motor development, but not mental development, in breast-fed infants.

Adult↗
PubMed1988

Verification of the fetal valproate syndrome phenotype.

We have evaluated 19 children who were exposed to valproic acid (VPA) in utero to look for manifestations of a fetal valproate syndrome (FVS), as proposed by Di Liberti et al. [1984]. We found no consistent alterations of pre- or postnatal growth with exposure to VPA monotherapy. Postnatal growth deficiency and microcephaly were present however, in two thirds of children exposed to VPA in combination with other anticonvulsants. Developmental delay or neurologic abnormality was found in 71% of those exposed to VPA monotherapy, and in 90% of those exposed to VPA and other anticonvulsants. Craniofacial anomalies, which can be seen with other anticonvulsant exposures, including midface hypoplasia, short nose with a broad and/or flat bridge, epicanthal folds, minor abnormalities of the ear, philtrum or lip, and micrognathia were also found in infants whose mothers used VPA. Prominent metopic ridge and outer orbital ridge deficiency or bifrontal narrowing and certain major anomalies such as tracheomalacia, talipes equinovarus (with intact spine) and lumbosacral meningomyelocele seem to be peculiar to infants with VPA exposure. Other defects such as urogenital anomalies, inguinal or umbilical hernias, and minor digital anomalies that are common to other prenatal anticonvulsant exposures are also occasionally found in those exposed to VPA. Heart defects have been found in infants exposed to nearly every class of anticonvulsant although the types of defects associated with maternal VPA use may be clarified when classified by pathogenetic mechanism. Our findings overall are in agreement with the report of Di Liberti et al. [1984].

Abnormalities, Drug-Induced↗
PubMed1988

Physical anomalies and developmental delays in nonhuman primate infants exposed to weekly doses of ethanol during gestation.

Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3, or 4.1 gm/kg from the 5th week. Mean maternal mean peak plasma ethanol concentrations (MPPEC) ranged from 24 +/- 6 mg/dl at the 0.3 gm/kg dose to 549 +/- 71 mg/dl at the 4.1 gm/kg dose. Thirty-three viable infants were followed from birth to 6 months of age and assessed for growth, health, congenital anomalies and developmental rate. Facial anomalies, growth deficiency, or central nervous system dysfunction were found in 57% of the alcohol-exposed animals. No animal showed all the features of the human fetal alcohol syndrome. Ten of the twelve animals (83%) with mean MPPEC above 140 mg/dl had evidence of a teratogenic impact. The animals with full gestational exposure to ethanol and mean MPPEC between 140 and 249 mg/dl had much more severe and consistent cognitive abnormalities than the animals with delayed gestational exposures, even though the latter were exposed to mean MPPEC between 260 and 540 mg/dl. Conclusions from this study included: 1) ethanol-related behavioral teratogenesis occurred without accompanying physical anomalies, 2) measurable teratogenic effects from weekly exposures occurred only at intoxicating doses of ethanol, and 3) early gestational exposure to ethanol appeared to be more damaging to cognitive function than later and considerably greater alcohol exposure.

Animals↗
PubMed1988

Morphometric analysis of Macaca nemestrina exposed to ethanol during gestation.

This study was part of a multidisciplinary investigation of the effects of gestational ethanol exposure in nonhuman primates. Thirty-one pregnant Macaca nemestrina were exposed to weekly ethanol doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg maternal weight. Dose cohorts 0.0 through 1.8 were exposed to the initial ethanol dose within 10 days postconception. Dose cohorts 2.5 through 4.1 received their initial dose after the fifth week of gestation. Morphometric analyses performed on cranial radiographs showed that animals exposed to high doses of gestational ethanol had, on average, slightly smaller, distorted crania than control animals. A dysmorphic, flat face characteristic of fetal alcohol syndrome was recognized in one animal of the 1.8 g/kg cohort. The animal that received the highest doses of gestational ethanol was microcephalic. Similar malformations were not seen with low ethanol exposures or in controls. These data suggest a pattern of cranial distortion that may be recognizable and characteristic of ethanol teratogenesis.

Animals↗
PubMed1987

Facial effects of fetal alcohol exposure: assessment by photographs and morphometric analysis.

This study was designed to assess the limits of alcohol-related facial dysmorphogenesis. Standard full face and lateral facial photographs were obtained on 21 7-year-old children who had been exposed gestationally to known, heavy quantities of ethanol. Only two of these children had been previously considered to have definite fetal alcohol syndrome (FAS). Similar photographs of 21 other 7-year-old children with negligible gestational ethanol exposure were obtained for control purposes. Copies of the 42 photographs were given to each of seven expert clinicians who were asked to select any child with an FAS-related facial appearance. Six of seven judges were accurate in identifying children with high levels of alcohol exposure as having a fetal alcohol-affected face. A set of homologous points on the photographs were then digitized and analyzed by newly developed morphometric methods to determine the facial shape characteristics that distinguish the selected photographs of highly exposed children. The analysis confirmed that the judges specifically identified children with facial changes consistent with those previously published as defining the face of the FAS: short palpebral fissures, a relatively long and flat midface, and a retrusive mandible. This methodology may be useful in more accurately delineating the facial phenotype in other conditions diagnosed primarily on the basis of subjective clinical criteria.

Anthropometry↗
PubMed1987

Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque (Macaca nemestrina).

Ethanol was orally administered once per week to gravid pig-tailed macaques (Macaca nemestrina) in doses of 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg. A control group received a sucrose solution, isocaloric and isovolemic to the highest ethanol dose. Pregnancy was followed after 116 possible conceptions in 54 females. Peak plasma ethanol concentrations (PPECs) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. An increased rate of spontaneous abortion was related to ethanol exposure at and above 1.8 g/kg (mean PPEC = 205 mg/dl). Pregnancy failure in the first 30 days of gestation increased at doses above 2.5 g/kg. The effect on pregnancy outcome of weekly exposure to ethanol in this nonhuman primate is comparable to available data on humans. The methodology of this study represents an effective model for studying ethanol teratogenesis in a nonhuman primate.

Abortion, Spontaneous↗
PubMed1987

Feeding infants with cleft lip, cleft palate, or cleft lip and palate.

In assessing 143 infants with cleft lip and palate, we found feeding problems to vary with the patients' anatomic lesion. Effective feeding techniques were identified by first assessing the infant's ability to generate negative intraoral pressure and to move the tongue against the nipple and then by matching these deficits to appropriate feeding devices.

Bottle Feeding↗