Ameliorative effects of supplemental folinic acid on Lamotrigine-induced fetal malformations in the mouse.

Data from our previous work indicate that Lamotrigine (LTG) is teratogenic in the mouse. In the present study, we attempted to determine the possible protective effects of exogenous folate on LTG-induced fetal anomalies in TO mouse. Experiment I entailed administering 4 mg/kg of folinic acid (FA) and (25 mg/kg) of LTG intraperitoneally three times on gestation day (GD) 8 to a group of mice; other groups were a group that received similar volumes of saline, a group that received LTG and Saline, a group that received FA and saline. Experiment 2 involved administering groups of mice with daily 3 doses FA (or proportionate volume of saline) on GD 5 through 10 and either 3 doses of saline on GD8, or 3 doses of LTG on GD8. Maternal plasma concentrations of FA, vitamin B12 and homocysteine were determined an hour after the last injection from one-half of all animals. The other half were allowed to go to term (GD18) when they were euthanized and their fetuses were examined for visceral and skeletal malformations. A high incidence of resorption, abortion, embryolethality, congenital malformations, and intrauterine growth restriction (IUGR), was observed in the LTG-treated group. Folic acid and B12 levels were decreased and homocysteine concentration increased significantly in LTG groups. Mice receiving LTG with FA had normal levels of folate, Vitamin B12 and homocysteine levels, and the fetuses had fewer birth defects similar to the controls which were given saline only. Supplemental FA ameliorated to a great extent the LTG-induced embryonic resorption and malformations and restored the FA status.

Nutrient intake of infants and toddlers in the United Arab Emirates: the Feeding Infants and Toddlers Study.

This descriptive study evaluated the nutrient adequacy of the diet of infants (aged 6-11.9 months) and toddlers (aged 12-24 months) in the United Arab Emirates. A random sample of 1000 infants and toddlers was recruited from 2 cities (Al Ain and Dubai) from March 2011 to February 2012 and their usual nutrient intake was determined using 24-hour recall. In all, 54.2% of infants and 25.2% of toddlers were breastfeeding. Mean energy intake of infant girls in Al Ain and Dubai was 747 (SD 189) kcal and 773 (SD 215) kcal respectively and 810.5 (SD 232.2) kcal and 821.9 (SD 262) kcal for boys. In toddlers, mean energy intake for girls in Al Ain and Dubai was 1032.8 (SD 252) kcal and 1013 (SD 339.1) kcal respectively and 1057.2 (SD 201.8) kcal and 1030.3 (SD 341.7) kcal for boys. Iron intake was low in both groups. Mean body mass index and body weight and height were similar to World Health Organization figures but significant numbers of infants and toddlers of both sexes were over- or underweight. Although mean energy and macronutrient intakes were comparable to the RDA, significant numbers were over- or underfed.

Public Perception Toward COVID-19 Disease Nature, Susceptibility to Complication, and Relationship to Influenza: A Cross-Sectional Study from Yemen.

Background: Following the coronavirus disease (COVID-19) declaration as a pandemic, Yemen has started applying preventive measures to prevent its spread. This study aims to identify the perception regarding the nature of the COVID-19 disease, susceptibility to severe forms of the disease, and its relationship to seasonal influenza among the population of Yemen. Methods: This was a cross-sectional study of the public in Yemen. The relationship between participants' sociodemographic factors and their responses was assessed by the chi-square test. Results: A total of 748 participants agreed to participate in the study. Regarding the nature of the diseases, nearly half of the participants (48.8%, n=352) believed that COVID-19 is a naturally occurring human virus that is a serious and fatal disease (61.2%, n=448). The majority (74.9%; n=518) did not agree that bacteria cause COVID-19. More than half of the participants (57.5%, n=423) believed this disease is transmitted to humans through a host animal. Regarding the vulnerable groups to develop severe COVID-19 infection, most of the participants pointed out that the elderly (94.3%, n=705), people with chronic diseases (89.9%, n=669), and pregnant women (53%, n=365) were more susceptible to severe diseases. Regarding symptoms, the majority (61.9%, n=458) of the participants agreed that the symptoms of COVID-19 are similar to those of seasonal influenza. Additionally, the majority (81.9%, n=579) agreed that some individuals develop more severe symptoms than seasonal influenza, particularly those with chronic illness. Gender, age, and education were found to be associated with participants' perceptions regarding the nature of the virus and susceptibility to severe disease. Conclusion: Participants demonstrate a good understanding of the nature and susceptibility to complications associated with COVID-19 disease and its relationship to influenza. However, the respondents with a lower level of education might require additional educational campaigns to improve their awareness of the disease.

Severe exfoliative erythema of malnutrition in a child with coexisting coeliac and Hartnup's disease.

Exfoliative erythema of malnutrition is a collective term for skin lesions caused by a combination of multiple deficiencies in vitamins, microelements, essential fatty acids and amino acids. We report a 3-year-old Iraqi girl with malnutrition due to coexisting coeliac and Hartnup's disease. On admission to hospital, she presented with kwashiorkor, anaemia, hepatitis and hypoalbuminia. She had severe skin changes with erythema, desquamation, erosions and diffuse hyperpigmentation involving the whole integument, particularly the perioral area, trunk and legs. She also had angular cheilitis, glossitis, conjunctivitis and diffuse alopecia. After treatment with a high-protein gluten-free diet and supplementation with vitamins and microelements there was a rapid improvement in the skin lesions. The severity of the skin lesions in this case can be explained by the coexistence of two metabolic diseases causing complex malnutrition.

Size at birth in a rapidly developing economy: intrauterine growth pattern of UAE infants.

BACKGROUND: Despite rapid economic growth and the recognition of intrauterine growth pattern as an important indicator of neonatal morbidity and mortality, the size at birth relative to gestation for UAE (United Arab Emirates) live births has not been investigated. AIM: The present study evaluated the intrauterine growth pattern of UAE infants and compared the data with the currently used reference standard. SUBJECTS AND METHODS: A total of 2497 singleton hospital live births to UAE mothers without pregnancy complications were studied. Anthropometric measurements and gestational age assessment of each infant were carried out according to standard procedures. The LMS computer program was used to construct perentile curves. RESULTS: The mean birth weight, length and head circumference of 1113 male term infants were 3298 g, 50.6 cm and 34.5 cm, respectively, and the same parameters for 1118 female term infants were 3201 g, 49.9 cm and 34.0 cm, respectively. These growth parameters were higher in males than females. Mean birth weight data were similar to those reported previously from a study from an economically developed community. The 10th percentile values were higher than in the currently used reference chart. CONCLUSION: Data on size at birth for UAE infants indicate that continuing use of the current reference chart may underestimate the prevalence of fetal growth failure in the population. Data from larger numbers of very preterm infants are needed to generate percentiles charts for very preterm infants.

Polymorphic N-acetyltransferase (NAT2) genotyping of Emiratis.

Polymorphic N-acetyltransferase (NAT2) genotypes were determined in 106 unrelated Emiratis by PCR-RFLP analysis to obtain estimates of allele frequencies. Thirteen different genotypes were found, four associated with the rapid acetylator phenotype and nine with the slow acetylator phenotype. Among 67 phenotypically slow acetylators, there was 100% concordance between phenotype and genotype. Among 39 phenotypically rapid acetylators, 37 possessed at least one wild type allele; a 95% concordance with genotype. Seven different NAT2 alleles associated with slow acetylation were found. The commonest was a NAT2*5 type (C481T) allele which occurred with a frequency of 0.53, a significantly higher frequency than has been reported for other ethnic groups. A second slow allele, a NAT2*6 type (G590A), occurred with a frequency of 0.21. The most common genotypes found were NAT2*5/*5 homozygotes, NAT2*5/*6 heterozygotes and NAT2*4/*5 heterozygotes with frequencies of 0.25, 0.25 and 0.22 respectively. The high overall prevalence of alleles associated with slow acetylation (173/212; 81.6%) among Emiratis is consistent with previously reported high frequency of the slow acetylator phenotype in Arabs. Two apparently new slow alleles were identified but have not yet been fully characterized. One appears to be a NAT2*5 variant allele. The other uncharacterized allele appears likely to contain an entirely new mutation associated with slow acetylation.

Abnormal folate metabolism and genetic polymorphism of the folate pathway in a child with Down syndrome and neural tube defect.

The association of neural tube defects (NTDs) with Down syndrome (trisomy 21) and altered folate metabolism in both mother and affected offspring provide a unique opportunity for insight into the etiologic role of folate deficiency in these congenital anomalies. We describe here the case of a male child with trisomy 21, cervical meningomyelocele, agenesis of corpus callosum, hydrocephaly, cerebellar herniation into the foramen magnum, and shallow posterior cranial fossa. Molecular analysis of the methylenetetrahydrofolate (MTHFR) gene revealed homozygosity for the mutant 677C-->T polymorphism in both the mother and child. The plasma homocysteine of the mother was highly elevated at 25.0 micromol/L and was associated with a low methionine level of 22.1 micromol/L. Her S-adenosylhomocysteine (SAH) level was three times that of reference normal women, resulting in a markedly reduced ratio of S-adenosylmethionine (SAM) to SAH and significant DNA hypomethylation in lymphocytes. The child had low plasma levels of both homocysteine and methionine and a reduced SAM/SAH ratio that was also associated with lymphocyte DNA hypomethylation. In addition, the child had a five-fold increase in cystathionine level relative to normal children, consistent with over-expression of the cystathionine beta synthase gene present on chromosome 21. We suggest that altered folate status plus homozygous mutation in the MTHFR gene in the mother could promote chromosomal instability and meiotic non-disjunction resulting in trisomy 21. Altered folate status and homozygous TT mutation in the MTHFR gene in both mother and child would be expected to increase the risk of neural tube defects. The presence of both trisomy 21 and postclosure NTD in the same child supports the need for an extended periconceptional period of maternal folate supplementation to achieve greater preventive effects for both NTD and trisomy 21.

Determination of amino acids by ion-exchange chromatography on filter paper spotted blood samples stored at different temperatures and for different periods: comparison with capillary and venous blood.

OBJECTIVE: To determine whether the well-established filter paper spotted blood method used for the determination of some amino acids could be reliably used to measure all amino acids and whether amino acid results thus obtained are reproducible and comparable to the results obtained by measuring plasma amino acids in either capillary or venous blood. METHODS: This is a prospective study in which blood samples from a finger-prick were collected in capillary tubes and at the same time blotted on filter papers; another sample was taken from a vein, from 19 healthy volunteers aged between 18 and 24 yr after a strict 12-h overnight fast. Another 9 healthy adult volunteers provided blood samples on filter papers for the storage study; 9 samples were analyzed immediately; 9, 8 and 4 samples were stored at -20 degrees C, -4 degrees C and room temperature respectively and analyzed after 14 days; 8 samples stored at -20 degrees C were analyzed after 4 weeks. RESULTS: Intra-sample reproducibility in the filter paper blood from the same individual was found to be mostly less than 20%, while for the capillary blood was less than 5%. The greatest variability was in cystine and methionine. There was no significant difference between results obtained from capillary blood and from venous blood, but there was a significant difference between amino acid concentrations in venous and capillary blood on the one hand and filter paper blood on the other. Storage at different temperatures and for a varied period of time showed little change except in serine, glutamate, ornithine, histidine, cystine and methionine. There was a 30% decrease in concentrations of most amino acids in filter paper blood when compared to capillary or venous blood probably because of loss in the extraction process. CONCLUSION: A new set of values for amino acids in filter paper blood in normal individuals is presented. Blood spotted filter paper could be used to screen practically all inborn errors of amino acid metabolism.

Group B streptococcal serotype distribution of isolates from colonized pregnant women at the time of delivery in United Arab Emirates.

OBJECTIVE: To determine the maternal colonization rate with group B streptococcus (GBS) and to identify the most frequent GBS serotypes occurring in UAE women during labour. STUDY DESIGN: From February 1998 to January 1999, five hundred and sixty three pregnant women from a similar socio-economic and ethnic population were enrolled for the study. High vaginal swab cultures for GBS were obtained at the time of admission for delivery. Isolates were classified according to their capsular polysaccharide types (Ia, Ib, Ic, II-V) and c protein antigen compound. RESULTS: Fifty-seven (10.1%) of 563 mothers were found to be carriers of GBS. Among the isolates, serotype IV (26.3%) predominated followed by type Ia (21.0%), type III (17.6%), type V (12.3%) and nontypeable, which accounted for 15.8%. CONCLUSIONS: In view of the unknown status for GBS carrier rates in our community, this study suggests that about 10% of UAE women are colonized with group B streptococcus at delivery. The serotype distribution of the isolates in this population is different than those reported elsewhere with type IV predominating followed by type Ia and III.

Abnormal myelination in peroxisomal isolated dihydroxyacetonephosphate acyltransferase deficiency.

The cranial magnetic resonance imaging findings in three siblings with nonrhizomelic chondrodysplasia punctata due to isolated dihydroxyacetonephosphate acyltransferase (DHAP-AT) deficiency are reported. Areas of high signal intensity in a patchy distribution on the T2-weighted images were detected in the centrum semiovale in the eldest patient (a 6-year-old girl). The white matter of the second child (a 5-year-old boy) was spared, whereas the youngest sibling (a 2-year-old boy) manifested very severe white matter abnormalities. DHAP-AT catalyzes the first step in the synthesis of plasmalogens, which are major constituents of myelin. Defective plasmalogen synthesis may have contributed to abnormal myelin formation in 2 patients. Because the clinical presentation of the child without detectable defect in myelination was similar to that of his siblings, the neurologic signs observed in isolated DHAP-AT deficiency cannot be attributed solely to the disturbances in the myelin formation.

Is the raised metabolic rate of the small for gestation infant due to his relatively large brain size.

Oxygen consumption at different stages of vigilance, and for the whole 24 h, was measured in 13 small-for-gestational age (SGA) and 16 appropriate-for-age (AGA) premature infants at ages of 4-25 days. Brain weight was calculated from head circumference measurements and expressed as percentage of body weight and was found to be significantly higher in SGA infants than AGA ones (14% +/- 2.1 (S.D.) in the SGA and 12.3% +/- 1.5 (S.D.) in the AGA infants). Metabolic rate (MR) was calculated and expressed as kcal/centimetre head circumference, kcal/g brain wt. and kcal/kg body wt. Whereas MR expressed in kg body wt. was significantly higher in SGA infants than in AGA ones, no difference could be detected in the values when MR was expressed as kcal/cm head circumference, or MR/g brain wt. The difference that exists in the metabolic rates between SGA and AGA infants can be minimised by using head circumference as a reference. Therefore, the apparently high MR found in SGA infants in the neonatal period can be attributed, in a major way, to their relatively large brain size.

Nutrient intake of infants and toddlers in the United Arab Emirates: the Feeding Infants and Toddlers Study

This descriptive study evaluated the nutrient adequacy of the diet of infants [aged 6-11.9 months] and toddlers [aged 12-24 months] in the United Arab Emirates. A random sample of 1000 infants and toddlers was recruited from 2 cities [Al Ain and Dubai] from March 2011 to February 2012 and their usual nutrient intake was determined using 24-hour recall. In all, 54.2% of infants and 25.2% of toddlers were breastfeeding. Mean energy intake of infant girls in Al Ain and Dubai was 747 [SD 189] kcal and 773 [SD 215] kcal respectively and 810.5 [SD 232.2] kcal and 821.9 [SD 262] kcal for boys. In toddlers, mean energy intake for girls in Al Ain and Dubai was 1032.8 [SD 252] kcal and 1013 [SD 339.1] kcal respectively and 1057.2 [SD 201.8] kcal and 1030.3 [SD 341.7] kcal for boys. Iron intake was low in both groups. Mean body mass index and body weight and height were similar to World Health Organization figures but significant numbers of infants and toddlers of both sexes were over- or underweight. Although mean energy and macronutrient intakes were comparable to the RDA, significant numbers were over- or underfed

La présente étude descriptive avait pour objectif d'évaluer la valeur nutritionnelle de l'alimentation des nourrissons [6 à 11,9 mois] et des jeunes enfants [12 à 24 mois] aux Emirats arabes unis. Un échantillon aléatoire de 1000 nourrissons et de jeunes enfants a été sélectionné dans deux villes [Al-Aïn et Dubaï] entre mars 2011 et février 2012, et leur apport nutritionnel habituel a été déterminé au moyen du rappel des 24h. Au total, 54,2% des nourrissons et 25,2% des jeunes enfants étaient allaités au sein. L'apport énergétique moyen des nourrissons de sexe féminin à Al-Aïn et Dubaï était de 757 kcal [ET 189] et de 773 kcal [ET 215] respectivement, et de 810,5 kcal [ET 232,2] et de 821,9 kcal [ET 262] pour les nourrissons de sexe masculin. Concernant les jeunes enfants, l'apport énergétique moyen des petites filles à Al-Aïn et Dubaï était de 1032,8 kcal [ET 252] et de 1013 kcal [ET 339,1] respectivement, et de 1057,2 kcal [ET 201,8] et de 1030,3 kcal [ET 341,7] pour les petits garçons. L'apport en fer était faible dans les deux groupes. L'index de masse corporelle ainsi que le poids corporel et la taille moyens étaient similaires aux chiffres de l'Organisation mondiale de la Santé, mais un nombre important de nourrissons et de jeunes enfants des deux sexes étaient en surpoids ou souffraient au contraire d'insuffisance pondérale. Bien que l'apport énergétique et l'apport en macronutriments moyens étaient comparables aux apports journaliers recommandés, un nombre important des sujets étaient sur ou sous-alimentés

Vigabatrin (VGB) administered during late gestation lowers maternal folate concentration and causes pregnancy loss, fetal growth restriction and skeletal hypoplasia in the mouse.

Vigabatrin (VGB) has several therapeutic advantages over older antiepileptic drugs (AED), but there is a lack of information about its potential reproductive toxicologic effects. Our aim was to evaluate the consequences of VGB administered during late gestation on fetal growth and development in the mouse. Based on the results of our previous study, we administered groups of mice a single dose of 450 mg/kg VGB on one of gestation days (GD) 15, 16 or 17. Fetuses were collected on GD 18. VGB groups had a significant incidence of fetal death, abortion, intrauterine growth restriction (IUGR), and hypoplasia of the axial skeleton, metacarpals, metatarsal and phalanges. Abortion was characterized by visible hemorrhagic expulsion of the embryos with their membranes. Maternal plasma folate (FA) and vitamin B12 concentrations were found to be markedly reduced within 12h of VGB treatment. Mice were supplemented with FA from GD 12 through GD 17 with or without a single dose of VGB on GD 15. This group had no abortions. Their fetuses had better body weight and lower frequency of IUGR than those of the non-supplemented VGB group. These data suggest that reductions in maternal FA and vitamin B12 concentrations play an important role in fetal loss, IUGR and skeletal hypoplasia induced by VGB during late gestation in the mouse. In view of the finding that a significant maternal toxicity is associated with this dose regimen, additional groups of mice were treated with 350 mg/kg VGB during embryogenesis and late gestation. This treatment was found to be maternally nontoxic. However, this low dose also resulted in significant fetal loss and IUGR when treatment occurred during late gestation. These data support the hypothesis that late gestation is particularly susceptible to VGB-induced fetal loss and IUGR in the mouse.

United Arab Emirates: communities and community genetics.

The UAE society is cosmopolitan, but the indigenous inhabitants are traditional with puritanical values despite their exposure to other vastly different cultures and habits. Marriages between consanguineous couples are still the norm rather than the exception. As a result, there is a high frequency of genetic disorders, particularly autosomal recessive types. Despite the high frequency of genetic disorders like haemoglobinopathies and others characteristically found in this population, genetic services are inadequate. Screening for certain disorders like thalassaemia are not applied on a wide scale. Abortion is illegal, and therefore, prenatal diagnosis or preconception tests are not done. With the absence of a good national database, deficiency of genetic services and absence of preventative alternatives for carrier couples, genetic counsellors find it difficult to advice pragmatic solutions to issues relating to genetic diseases. This paper reviews common genetic problems in the UAE with special emphasis on available genetic services and support to families with children with inherited disorders. Existing barriers to the improvement of clinical services by prenatal counselling are also discussed.

Respiratory metabolism in preterm infants: the measurement of oxygen consumption during prolonged periods.

We have developed a method for measuring oxygen consumption (Vo2) in preterm infants in their normal incubator environment over prolonged periods. The results of measurements made over 24 h in 18 infants are presented. In normally grown infants, the mean Vo2 was 9.66 +/- 1.25 liters/kg X 24 h (SD) (6.71 +/- 0.87 ml/kg X min), and in small for gestation infants it was 10.09 +/- 1.21 liters/kg X 24 h (7.00 +/- 0.84 ml/kg X min). During the 24-h measurements, the highest mean Vo2 during 3 consecutive h was 7.75 +/- 0.89 ml/kg X min and the lowest was 5.95 +/- 0.92 ml/kg X min. The difference between the highest and the lowest values was significant (p less than 0.001). There is room for considerable error if short term measurements are assumed to represent values over a whole day. "Short" measurements should be made over at least 6 h.

Could final year school grades suffice as a predictor for future performance?

The performance of three groups of medical students was evaluated at the end of one phase of their studies--after 2 years of premedicine. The aim of the study was to determine whether any of the assessment methods--secondary school grades, entrance examination or test for proficiency in the English language, used for selection of medical students, could reliably predict student performance in the early stages of their education. A significant correlation was found between secondary school grades and the entrance exam on the one hand and grade point average (GPA) on the other. However the results of the test for English proficiency did not correlate with the GPA. It is concluded that the secondary school grade on its own is a good predictor of academic performance in the early stages of medical undergraduate education.

A study of the attitudes of the foundation staff of a new medical faculty to problem-based learning.

The characteristics of the foundation staff of the United Arab Emirates (UAE) University Faculty of Medicine numbering 18 were studied using open-ended questions in an interview setting. All were experienced academically with mean total years of experience being more than 20 years. The mean age of 51.7 years indicated that the majority of staff interviewed were in the latter stage of their academic career. Although one of the criteria for accepting candidates was flexibility in their outlook to new teaching learning systems and positive attitudes to problem-based learning (PBL), only seven understood PBL and five were openly hostile to the system. The reasons for joining the Faculty were protean, but most saw the job as being challenging in nature and a change from routine. The question is raised whether the selection procedure was appropriate and whether more stringent criteria might have been applied, to have included attitudinal aspects in addition to the academic achievements of the candidates, for the rightly motivated and oriented individual to be appointed.

Stool water in preterm neonates.

Data are presented on faecal water losses in 93 preterm infants being fed breast milk (72 infant days) or formula (280 days). Losses per kg increased to 4 weeks, when they amounted to 11% of water requirement in infants fed breast milk and 8% in infants fed formula.

Primary infantile hypomagnesaemia; report of two cases and review of literature.

We describe two male infants suffering from primary hypomagnesaemia, diagnosed at 3 months and 2.5 months of age. They both presented with generalised convulsions, with case 2 exhibiting hypocalcaemia which did not respond to calcium and case 1 having normocalcaemia at first but hypocalcaemia 3 days after admission. Both improved dramatically after initiation of magnesium therapy. A carrier-mediated transport defect is the most likely cause of this disease. It is of the utmost importance that a correct and prompt diagnosis be made as therapy is simple and effective. Failure in diagnosing this condition could prove fatal as demonstrated in the family history of case 2.

Teratogenic effects of vigabatrin in TO mouse fetuses.

Vigabatrin (VGB) is a relatively recently introduced antiepileptic drug that enhances the brain levels of gamma aminobutyric acid (GABA). Few data on its teratogenic effects appear to have been reported. Our objective was to determine if VGB was teratogenic in the TO mouse. Single doses of 300-600 mg/kg of VGB dissolved in saline were administered intraperitoneally (IP) to groups of TO mice on one of gestation days (GD) 7-12. The controls were saline treated or untreated. No maternal toxic effects were observed in the 300 or 450 mg/kg groups, and the 600 mg/kg dose was totally lethal to the mothers. Fetuses were collected on GD 18. Both 300 and 450 mg/kg doses induced a consistently significant intrauterine growth retardation irrespective of the developmental stage at administration. VGB did not augment the spontaneous incidence of neural tube defects characteristic of this strain, but accelerated destruction of the brain in spontaneous exencephalic embryos. Mandibular and maxillary hypoplasia, arched palate, cleft palate (two cases), limb defects (one case), and exomphalos were observed in the malformed fetuses. The high incidence of exomphalos appears to be a unique result of VGB treatment. Alizarin red-S/alcian blue-stained, skeletons revealed hypoplasia of mid facial bones, stage-dependent increase in the frequency of cervical and lumbar ribs, rib fusion, and sternal and vertebral malformations in the drug-treated fetuses. Middle and distal phalanges of the forepaw and mid phalanges and tarsals of the hindpaw failed to ossify in a significant number of experimental fetuses. Homeotic shift in terms of presacral vertebral number and a high incidence of lumbar and cervical ribs in the treated group are suggestive of treatment-related alterations in gene expression. In view of the paucity of human and animal data on the reproductive toxicologic effects of VGB, the results of the present study assume particular importance and suggest that VGB should be used in pregnancy with extreme caution.