Biomedical subjects

A Ornoy

Publications and source records attributed to A Ornoy.

At least 19 recordsLinked to original sources

PubMed2005

Sexual dimorphism of growth plate prehypertrophic and hypertrophic chondrocytes in response to testosterone requires metabolism to dihydrotestosterone (DHT) by steroid 5-alpha reductase type 1.

Rat costochondral growth plate chondrocytes exhibit sex-specific and cell maturation dependent responses to testosterone. Only male cells respond to testosterone, although testosterone receptors are present in both male and female cells, suggesting other mechanisms are involved. We examined the hypothesis that the sex-specific response of rat costochondral cartilage cells to testosterone requires further metabolism of the hormone to dihydrotestosterone (DHT). Resting zone (RC) and growth zone (GC, prehypertrophic and upper hypertrophic zones) chondrocytes from male and female Sabra strain rats exhibited sex-specific responses to testosterone and DHT: only male cells were responsive. Testosterone and DHT treatment for 24 h caused a comparable dose-dependent increase in [3H]-thymidine incorporation in quiescent preconfluent cultures of male GC cells, and a comparable increase in alkaline phosphatase specific activity in confluent cultures. RC cells responded in a differential manner to testosterone and DHT. Testosterone decreased DNA synthesis in male RC cells but DHT had no effect and alkaline phosphatase specific activity of male RC cells was unaffected by either hormone. Inhibition of steroid 5alpha-reductase activity with finasteride (1, 5, or 10 microg/ml), reduced the response of male GC cells to testosterone in a dose-dependent manner, indicating that metabolism to DHT was required. RT-PCR showed that both male and female cells expressed mRNAs for steroid 5alpha-reductase type 1 but lacked mRNAs for the type 2 form of the enzyme. Male cells also exhibited 5alpha-reductase activity but activity of this enzyme was undetectable in female cells. These observations show that sex-specific responses of rat growth zone chondrocytes to testosterone requires the further metabolism of the hormone to DHT and that the effect of DHT in the male growth plate is maturation-state dependent. Failure of female chondrocytes to respond to testosterone may reflect differences in testosterone metabolism, since these cells possess greater ability to aromatize the hormone to estradiol.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2005

The effect of 6-mercaptopurine on early human placental explants.

BACKGROUND: 6-mercaptopurine (6-MP) is an antineoplastic and immunosuppressive drug. Recently, more women have received this drug during pregnancy. Animal studies have shown that 6-MP has deleterious effects on the fetus, while human data include prematurity, intrauterine growth restriction, low birth weight and malformations that occur especially when the drug is administered in the first trimester of pregnancy. OBJECTIVES: To study the effects of 6-MP on cellular functions of human trophoblast explants. METHODS: Human placental explants (5.5-9 weeks gestational age), that were grown on matrigel, were exposed to medium containing 6-MP for 5 days. Medium alone served as control. Extravillous trophoblast (EVT) cell migration assessment was performed by visual observation. Analysis of proliferating events of the trophoblast cells was assessed by immunohistochemical examination. Apoptosis was analyzed by Tunnel procedure and by anti-caspase 3 staining and hormone level by enzyme-linked immunosorbent assay. RESULTS: 6-MP inhibited migration of EVT cells from the villi to the matrigel with a lower proliferation rate and increased apoptosis of cytotrophoblast cells compared to controls. However, no significant effect of 6-MP on hormone levels was observed. CONCLUSIONS: 6-MP inhibited migration and proliferation of trophoblast cells in first-trimester human placental explant culture.

Antimetabolites, Antineoplastic↗

PubMed2005

The safety of proton pump inhibitors in pregnancy: a multicentre prospective controlled study.

BACKGROUND: Proton pump inhibitors are used to treat gastro-oesophageal reflux and peptic ulcers. Gastro-oesophageal reflux is a common condition in pregnancy. Human pregnancy experience with lansoprazole or pantoprazole is very limited. More data exist on the safety of omeprazole in pregnancy. AIM: To assess the safety of proton pump inhibitors in pregnancy. METHODS: The rate of major anomalies was compared between pregnant women exposed to omeprazole, lanzoprazole, or pantoprazole and a control group counselled for non-teratogens. The study design is a multicentre (n = 8), prospective, controlled study of the European Network of Teratology Information Services. RESULTS: We followed up 295 pregnancies exposed to omeprazole [233 in the first trimester (T1)], 62 to lansoprazole (55 in T1) and 53 to pantoprazole (47 in T1), and compared pregnancy outcome to that of 868 European Network of Teratology Information Services controls. The rate of major congenital anomalies did not differ between the exposed and control groups [omeprazole nine of 249 (3.6%), lansoprazole two of 51 (3.9%) and pantoprazole one of 48 (2.1%) vs. controls 30 of 792 = 3.8%]. No differences were found when exposure was limited to the first trimester after exclusion of genetic, cytogenetic or infectious anomalies. CONCLUSIONS: This study suggests that proton pump inhibitors do not represent a major teratogenic risk in humans.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2005

Growth-plate chondrocytes respond to 17beta-estradiol with sex-specific increases in IP3 and intracellular calcium ion signalling via a capacitative entry mechanism.

17Beta-estradiol (E(2)) regulates growth-plate chondrocyte differentiation in a gender and cell maturation-dependent manner via classic nuclear receptors ERalpha and ERbeta, and membrane-associated signalling. Here we show that sex-specific effects of E(2) involve changes in intracellular calcium concentration (ICCC). Resting-zone chondrocytes (RC) and growth-zone chondrocytes (GC) were isolated from costochondral cartilage of male and female rats. Confluent cultures were treated with 10(-8)M E(2) or 17alpha-estradiol in the presence of high and low extracellular Ca(2+) concentration. The ICCC was determined using laser scanning confocal microscopy to measure changes in Fluo-4 fluorescence every 5s for a total of 500s. E(2) increased ICCC in the cells from female rats but had no effect on ICCC in male cells. The effect was rapid (peak at 140s) and stereospecific. E(2) increased ICCC in RC and GC chondrocytes but the effect was greater in RC cells. Low Ca(2+) media did not abolish the E(2)-dependent ICCC elevation, nor did inclusion of verapamil, which inhibits Ca(2+) channels on the cell membrane. Thapsigargin reduced the effect of E(2) on ICCC, showing that Ca(2+) pumps on the endoplasmic reticulum were involved. Pre-treatment of the cells with the ER antagonist ICI 182780 did not alter the stimulatory effect of E(2), suggesting that traditional estrogen receptor mechanisms do not play a role. E(2) caused rapid production of inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) but only in female cells, and the effect was greater in RC chondrocytes. These results indicate that E(2) regulates ICCC in a sex-specific and cell maturation state-dependent manner. The mechanism is membrane-associated and is mediated by PLC-dependent IP3 production and release of Ca(2+) from the endoplasmic reticulum.

Aniline Compounds↗

PubMed2003

The impact of intrauterine exposure versus postnatal environment in neurodevelopmental toxicity: long-term neurobehavioral studies in children at risk for developmental disorders.

Various investigators have shown that enriched environment may positively affect the early brain development of experimental animals. Environment was also shown to positively affect the development of young children born to mothers of low socio-economic class (low SES). It is unknown, however, to what extent can an enriched environment improve the developmental outcome of children born with slight brain damage. We studied the development of preschool and early school age children born to heroin dependent parents raised at home or adopted in comparison to children suffering only from environmental deprivation (low parental SES) and to controls. They were examined by several professionals, using standard, age appropriate, neurological and psychological tests. Similar evaluations were performed on a group of early school age children born to mothers with pregestational or with gestational diabetes and on a group of children born prematurely, with a birth weight of less than 1500 g using various developmental tests. Young children born to heroin dependent mothers and fathers raised at home and children of low SES had, in comparison to controls, lower intellectual skills and a higher rate of inattention. This persisted at school age, too. Children born to heroin dependent mothers adopted at a young age and hence being raised in a good environment had normal intellectual function but a high rate of inattention and behavioral problems. We also examined the school age children for possible presence of ADHD and found a high rate of ADHD among all children born to heroin dependent parents including those adopted, as well as in the children with low parental SES. Similar findings regarding the strong positive influence of an enriched environment were observed in children born to diabetic mothers, where the intellectual abilities of the children were directly related with parental education. The cognitive abilities of the children born prematurely were also strongly associated with parental education and not with the degree of perinatal complications. In conclusion, in all groups of children at high risk for developmental problems was found that the environment has a strong influence on their intellectual abilities but not on motor skills or attention span. A good environment (high parental SES) may significantly improve the outcome.

Child↗

PubMed2003

Repair behavior in children with intellectual impairments: evidence for metalinguistic competence.

This paper tested the prediction that children with cognitive impairments who can use language intentionally will be able to carry out the metalinguistic operations involved in speech monitoring and repair. The specific linguistic characteristics of responses to requests for clarification given by 4 children with lower than normal IQ, ages 3 years 5 months to 6 years 10 months, were investigated. The analysis focused on children's ability to locate the specific errors that provoked neutral requests for clarification and produce repair. Three children could locate their errors and partly succeed in providing repair. It is suggested that ability to perform metaprocedures such as are implicated in repair behavior may be preserved in children with intellectual disabilities and that this ability does not implicate conscious awareness, nor does it depend on mature linguistic competence.

Child↗

PubMed2003

A simple method of culture of 11.5-day-old rat embryos in DMEM/F12 and 20% fetal bovine serum.

Post-implantation mouse and rat embryos are usually cultured in sera obtained from various rodents and from humans. We describe here a simple and inexpensive culture medium--Dulbecco's minimal essential medium/Ham's F12 (DMEM/F12) supplemented with 20% fetal bovine serum (FBS)--in which E11.5 rat embryos of the Hebrew University Sabra strain grow for 28 h slightly better than in heat-inactivated 90% rat serum with 10% distilled water and addition of 1 mg mL(-1) glucose. They have good growth and development and a low rate of anomalies, similar to that observed in embryos cultured on rat serum. Their size, total score and olfactory system development is slightly higher than in rat embryos cultured in rat serum. About 7.2% of these embryos exhibit subcutaneous haemorrhages in various areas, but these do not seem to interfere with their growth and development. This method is not appropriate for younger embryos; in E10.5 embryos cultured for 28 h we found increased embryonic death and anomalies.

Animals↗

PubMed2003

The effects of antiphospholipid antibodies obtained from women with SLE/APS and associated pregnancy loss on rat embryos and placental explants in culture.

Recurrent fetal loss occurs in approximately 1% of women. Autoimmune causes have been suggested as a factor in some of these cases. High rates of intrauterine fetal growth retardation and increased incidence of prematurity is associated with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). We found in previous studies that sera from SLE/APS patients when used as a culture medium for rat embryos were found to reduce embryonic growth and development, induce a high rate of embryonic anomalies and death and damage the yolk sac morphologically and functionally. In order to investigate the direct effect of IgG purified from women with SLE/APS on the growth and viability of embryos, we cultured 11.5-day-old rat embryos in their yolk sacs in the presence of IgG purified from SLE/APS patients with recurrent pregnancy loss (RPL). The IgG affected directly the embryo and yolk sac, reducing their growth. The purified IgG positive for anticardiolipin/anti-DNA antibodies reduced yolk sac and embryonic growth more than sera negative for these antibodies but positive for antiphosphatydilserine and for antilaminin. Monoclonal antiphosphatydilserine reduced yolk sac growth but the embryos remained intact. Following the observed damage to the yolk sac we cultured human placental explants at 5.5-8 weeks of pregnancy in sera from SLE/APS patients for 96 hours and found that these sera reduced placental trophoblastic cell growth, reduced their proliferation rate and increased their rate of apoptosis. Successful treatment of the women resulted in a correction of the damage induced in the cultured rat embryos and in the cultured placental explants.

Abortion, Habitual↗

PubMed2002

Diabetes teratogenicity in mice is accompanied with distorted expression of TGF-beta2 in the uterus.

Early embryonic deaths as well as malformed newborns are among complications of the diabetic pregnancy. Cytokines and growth factors operating in the embryonic vicinity are found to be among factors that determine the sensitivity of embryos to external and internal detrimental stimuli, including diabetes. Transforming Growth Factor-beta2 (TGF-beta2) has been shown to be essential for embryonic development and survival. In the present work, we evaluated the pattern of TGF-beta2 expression in the uterus of streptozotocin-induced diabetic mice, demonstrating a decreased reproductive performance and elevated percentage of litters with severely malformed fetuses. Since stimulation of the maternal immune system was found to increase the resistance of mouse embryos to the teratogenic effect of diabetes, the effect of immunopotentiation on the expression of the cytokine was also investigated. TGF-beta2 expression was studied at the mRNA level by using the in situ hybridization technique and at the protein level by using the immunohistochemical analysis. A clear decrease in TGF-beta2 mRNA expression in the uterus of diabetic mice was observed at examined time points: days 1, 5, and 9 of pregnancy. Also, an evident reduction in TGF-beta2, the protein expression in the uterus of diabetic mice, was demonstrated at these time points. Maternal immunopotentiation that improved the reproductive performance of diabetic mice and reduced the number of the litters with malformed fetuses was also accompanied by a clear increase in the level of TGF-beta2 mRNA expression in the pregnant uteri. The above results clearly demonstrate that the embryotoxic effect of diabetes is accompanied by an alteration of TGF-beta2 expression. Immunopotentiation that was shown to improve the reproductive performance of the diabetic mice was accompanied by a partial normalization of TGF-beta2 expression in embryonic vicinity.

Animals↗

PubMed2002

The effects of IgG purified from women with SLE and associated pregnancy loss on rat embryos in culture.

PROBLEM: Recurrent fetal loss occurs in approximately 1% of women. Autoimmune causes have been suggested as a factor in some of these cases. High rates of intrauterine fetal growth retardation and increased incidence of prematurity is associated with systemic lupus erythematosus (SLE) and the anti-phospholipid syndrome (APS). Autoantibodies from sera of SLE/APS patients affect reproductive outcome in pregnant mice, as was studied in vivo, where injection of immunoglobulin (Ig)G purified from patients with APS to mice caused fetal resorptions and growth retardation. METHODS: In order to investigate the direct effect of IgG purified from women with SLE or APS on the growth and viability of embryos, we cultured 11.5-day old-rat embryos in their yolk sacs in the presence of IgG purified from SLE and APS patients. RESULTS: IgG purified from SLE and recurrent pregnancy loss (RPL) patients affected directly the embryo and yolk sac reducing their growth. The purified IgG positive for anti-cardiolipin/anti-DNA antibodies reduced yolk sac and embryonic growth more than sera negative for these antibodies. CONCLUSION: Various antiphospholipid antibodies affect differently the growth and development of the embryo and the placenta.

Animals↗

PubMed2001

Is carbamazepine teratogenic? A prospective controlled study of 210 pregnancies.

The Israeli Teratogen Information Service prospectively followed up 210 pregnancies with first trimester carbamazepine exposure. Pregnancy outcome was compared with that of two overlapping controls, matched and general (n = 629), exposed to nonteratogenic agents. Our study suggests a twofold increase in the rate of major congenital anomalies (12/160 [carbamazepine] versus 18/560 [general control]; relative risk 2.24; 95% CI 1.1-4.56) and a birth weight reduction of approximately 250 g after in utero exposure to carbamazepine.

Abnormalities, Drug-Induced↗

PubMed2001

Pregnancy outcome after gestational exposure to metronidazole: a prospective controlled cohort study.

BACKGROUND: Metronidazole is an important antibacterial agent commonly used in women of reproductive age. Its use in pregnancy is a reason for concern for women and their health care providers. The objective was to examine the fetal safety of metronidazole. METHODS: The Israeli Teratogen Information Service prospectively collected and followed up 228 women exposed to metronidazole in pregnancy, 86.2% of whom with first-trimester exposure. Pregnancy outcome was compared with that of a control group, who were counseled during the same period for nonteratogenic exposure. RESULTS: There was no difference in the rate of major malformations between the groups (3/190; 1.6% [metronidazole] vs. 8/575; 1.4% [control], P = 0.739). The rate of major malformations did not differ between the groups even after including elective terminations of pregnancy due to prenatally diagnosed malformations (5/192; 2.6% [metronidazole] vs. 12/579; 2.1% [control], P = 0.777). A reduced neonatal birth weight was found in the metronidazole group compared with controls without significant differences in the rate of prematurity or in gestational age at delivery. The mean birth weight was lower in the metronidazole group when comparing the subgroup of term infants. CONCLUSIONS: This study confirms that metronidazole does not represent a major teratogenic risk in humans when used in the recommended doses.

Abnormalities, Drug-Induced↗

PubMed2001

Vitamins C and E improve rat embryonic antioxidant defense mechanism in diabetic culture medium.

BACKGROUND: Diabetes teratogenicity seems to be related to embryonic oxidative stress and the extent of the embryonic damage can apparently be reduced by antioxidants. We have studied the mechanism by which antioxidants, such as vitamins C and E, reduce diabetes-induced embryonic damage. We therefore compared the antioxidant capacity of 10.5-day-old rat embryos and their yolk sacs cultured for 28h in diabetic culture medium with or without vitamins C and E. METHODS: The embryos were cultured in 90% rat serum to which 2mg/ml glucose, 2mg/ml beta hydroxy butyrate (BHOB) and 10 microg/ml of acetoacetate were added. Rat embryos were also cultured in a diabetic medium with 25 microg/ml of vitamin E and 50 microg/ml of vitamin C. Control embryos were cultured in normal rat serum with or without vitamins C and E. RESULTS: Decreased activity of Cu/Zn superoxide dismutase (SOD) and of catalase (CAT) in the "diabetic" embryos and their yolk sacs, and reduced concentrations of low molecular weight antioxidant (LMWA) were found. Under these conditions we also found a decrease in vitamin C and vitamin E concentrations in the embryos, as measured by HPLC. In situ hybridization for SOD mRNA showed a marked reduction of SOD mRNA in the brain, spinal cord, heart and liver of embryos cultured in diabetic medium in comparison to controls. Following the addition of vitamins C and E to the diabetic culture medium, SOD and CAT activity, the concentrations of LMWA, the levels of vitamin C and E and the expression of SOD mRNA in the embryos and yolk sacs returned to normal. CONCLUSIONS: Diabetic metabolic factors seem to have a direct effect on embryonic SOD gene and perhaps genes of other antioxidant enzymes, reducing embryonic endogenous antioxidant defense mechanism. This in turn may cause a depletion of the LMWA, such as vitamins C and E. The addition of these vitamins normalizes the embryonic antioxidant defense mechanism, reducing the damage caused by the diabetic environment.

Animals↗

PubMed2001

Age and gender specific stimulation of creatine kinase specific activity by gonadal steroids in human bone-derived cells in culture.

We previously reported a non-enzymatic method for isolation of human bone cells in culture that display osteoblastic features and respond to 1,25 dihydroxy vitamin D (1,25) and to parathyroid hormone (PTH). The present study was undertaken to analyze the response of cultured human bone cells to 17beta-estradiol (E2) and to dihydrotestosterone (DHT) as a function of gender and age. Cultured human bone cells, obtained from biopsies during orthopedic surgery, were divided into four groups defined by gender and age: pre- and post-menopausal healthy non-osteoporotic women that were not under hormone replacement therapy (HRT) and mature (<55-year-old) and older (>60-year-old) men. We found gender specific responses to gonadal steroids using the specific activity of the brain type (BB) isozyme of creatine kinase (CK) as a response marker. Constitutive levels of CK activity did not change with age or gender and the enzyme extracted from cells from the different sexes and ages did not respond to either progesterone (P) or to 1,25. CK from the different cells responded to gonadal steroids in a gender specific manner, i.e. CK from female derived cells responded to E2 only and the enzyme from male derived cells responded to DHT only. In female derived cells the response to E2 declined significantly with age, while the response to DHT in CK from male derived cells did not vary with age. This may be due to either decreased proportion of mature osteoblasts and/or their differentiation state and/or changes in the levels of estrogen receptor(s), coactivators or corepressors in these cells. These results extend our knowledge of human osteoblast biology (beyond murine cells) and are therefore more relevant for developing models for treatment of human metabolic bone diseases such as post-menopausal osteoporosis.

Aging↗

PubMed2001

Developmental outcome of school-age children born to mothers with heroin dependency: importance of environmental factors.

Development of children aged 5 to 12 years born to mothers with heroin dependency raised at home or adopted was studied in comparison with: (1) children with environmental deprivation alone (i.e. low parental socioeconomic status [SES] and evidence of neglect), (2) children born to fathers with heroin dependency fathers, and (3) control individuals of average SES. One hundred and sixty children (84 males and 76 females; average age at examination 8 years) were evaluated between 1998 and 1999. All were attending mainstream schools. All participants were examined by a paediatrician and a psychologist using standard neurological and psychological age-appropriate tests, as well as tests and questionnaires to assess learning ability and attention span. The Conners and Achenbach questionnaires and the Pollack Taper test were used to assess possible presence of attention-deficit-hyperactivity disorder (ADHD). Mothers were assessed for ADHD using Wender's questionnaire. Children born to parents with heroin dependency raised at home and those of low SES exhibited intellectual impairment both on verbal and performance skills. They also had impaired reading and arithmetic skills. Children born to mothers with heroin dependency but who were adopted at a young age had normal intellectual and learning abilities, except for some reduced function on the performance Wechsler Intelligence Scale for Children-Revised. We found a high rate of ADHD among all children born to parents with heroin dependency, including those adopted, as well as in children with low parental SES. The highest rate of ADHD was in children born to mothers with heroin dependency raised at home, being twice that observed in the other groups. Mothers of these groups of children also had a high rate of ADHD.

Adult↗

PubMed2001

The association between anti-thyroid antibodies and pregnancy loss.

The incidence of thyroid autoantibodies in women with recurrent fetal loss, infertility or women who miscarried appears to be increased compared with controls of reproductive age without previous abortions. There are few working hypotheses concerning the asociation between anti-thyroid antibodies and the increased risk for pregnancy loss. The first hypothesis suggests that women with high titers of anti-thyroid antibodies have underlying very mild thyroid "under function". Another theory views the anti-thyroid antibodies as simply secondary markers of a predisposition of autoimmune disease rather than the actual cause of pregnancy loss. An evolutionary explanation suggests that reproductive problems in women with high titers of autoantibodies exist in order to prevent the transmission of autoimmune genes to the next generation. The reason for the association between pregnancy loss and thyroid immunity is still not clear. The working hypotheses above supply multi-factorial explanations, which could act together, may even be in synergy, as the propulsion for the pregnancy loss. Until today the mechanism by which anti Tg are responsible for pregnancy loss is not clear. Induced animal models with high titier of anti Tg could provide direct evidence for the pathogenic role of anti-thyroid antibodies and the mechanism that is responsible for the pregnancy loss in autoimmune thyroiditis. In the current presentation we describe data concerning the association between anti-thyroid antibodies and pregnancy loss, and hypothesis which explains this association.

Abortion, Spontaneous↗

PubMed2001

Expression of tumor necrosis factor-alpha in the pregnant uterus of diabetic mice: effect of maternal immunopotentiation.

PROBLEM: Tumor necrosis factor (TNF)-alpha mRNA and protein are expressed in the pregnant uterus of streptozotocin-induced diabetic mice at various stages of pregnancy. We intend to characterize their pattern and to evaluate whether the potentiation of the maternal immune system alters the pattern of the expression of the cytokine. METHOD OF STUDY: Diabetes was induced in ICR mice by streptozotocin injection. To modulate maternal immune responses, ICR mice were injected intrauterine with rat splenocytes 3 weeks before mating. The expression of TNF-alpha mRNA and protein was evaluated by in situ hybridization and immunohistochemistry techniques. RESULTS: The population of diabetic mice used in this study demonstrated a reduction in pregnancy rate and an increased number of litters with severely malformed fetuses. It has been observed that these disturbances are associated with a clear increase in TNF-alpha mRNA and protein expression in the uterus of these mice. Maternal immunopotentiation, while improving reproductive performance of these diabetic mice, was found to be accompanied by a reduced expression of TNF-alpha, both at the mRNA and protein level. CONCLUSIONS: The results of the present study suggest a possible involvement of TNF-alpha in mechanisms underlying diabetes-associated dismorphogenesis. Normalization of TNF-alpha expression by maternal immunopotentiation might represent a mechanism mediating its protective effect against diabetes-induced embryotoxic insult.

Animals↗

PubMed2001

School-age children born to diabetic mothers and to mothers with gestational diabetes exhibit a high rate of inattention and fine and gross motor impairment.

OBJECTIVES: To study the neurobehavioral effects that pregestational and gestational diabetes might have on offspring at school age. STUDY DESIGN: We studied neurobehavioral function at school age of 57 children born to 48, well controlled, diabetic mothers and of 32 children born to 32 women with gestational diabetes. Their development was compared with 57 control children matched by age, birth order and parental socio-economic status, using a number of cognitive, behavioral, sensory and motor neurological tests. RESULTS: The IQ scores on the WISC-R and Bender tests of the children born to diabetic mothers were similar to those of control children, but the Bender scores of the children born to mothers with gestational diabetes were slightly lower. No differences were found between the study groups in various sensory-motor functions in comparison to controls. However, both study group children performed less well than controls in fine and gross motor functions as observed on the Bruininks-Oseretzki test of motor proficiency. The scores of children born to the mothers with pregestational diabetes were higher than controls on the Touwen & Prechtl neurological examination (worse function). The children from both research groups also performed worse on the Pollack taper test that is designed to detect inattention and hyperactivity. The children of the two study groups also had slightly higher scores on the Conners abbreviated parents-teachers questionnaire measuring hyperactivity and inattention, but the differences from controls were not statistically significant. We found a negative correlation between the performance of the children born to mothers with pregestational diabetes on various neurodevelopmental and behavioral tests and the severity of maternal hyperglycemia as assessed by blood glycosylated hemoglobin levels and acetonuria. CONCLUSIONS: Pregestational or gestational diabetes was found to adversely affect attention span and motor functions of offspring at school age, but not their cognitive ability. These effects were negatively correlated with the degree of maternal glycemic control, and were more pronounced in younger children.

Adult↗