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PubMed2006

[Pharmacologic therapy of depression during pregnancy].

The pregnancy is considered to be relatively high risk period for depressive episodes in women, particularly for those with pre-existing affective disorders. Epidemiological studies indicate that between 10% to 16% of pregnant women fulfil the diagnostic criteria for major depression and on average 20% is affected by an anxiety disorder. Pharmacological treatment of depression during pregnancy, however, brings with it certainties and dilemmas. It has been reported that untreated depression is associated with impaired feto-placental function, premature delivery, miscarriage, low fetal growth and perinatal unwanted effects. On the other hand, the use of antidepressant drugs in pregnancy might be at risk of major malformations (teratogenesis), neonatal toxicity, especially withdrawal symptoms and neuropsychological-behavioural impairment. In addition, the abrupt discontinuation of antidepressants, because of fear for adverse fetal effects, exposes women to serious clinical problems, in particular the disease relapse. A number of reviews indicates that among antidepressant drugs, the older SSRIs (in particular fluoxetine, sertraline, citalopram) seem to be avoided of teratogenic risks; for these reasons such drugs are nowadays considered of choice for the treatment of depression during pregnancy. Less information is available for other drugs, including triciclycs, venlafaxine, mirtazapine, bupropion, escitalopram and duloxetine. Withdrawal symptoms have been reported for all antidepressants; these symptoms, however, were self-limiting in majority of cases and had a favourable outcome. Inconclusive findings emerge, so far, from the few longitudinal studies focusing on the long-term neurodevelopment outcome in children.

Abnormalities, Drug-Induced↗
PubMed2006

A meta-analysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 in the United States.

BACKGROUND: Thimerosal is an ethylmercury-containing compound (49.6% mercury by weight) used as at the preservative level in vaccines (0.005% to 0.01%). METHODS: Statistical modeling in a meta-analysis epidemiological assessment of the Vaccine Adverse Event Reporting System (VAERS) for neurodevelopment disorders (NDs) reported following Diphtheria-Tetanus-whole-cell-Pertussis (DTP) vaccines in comparison to Diphtheria-Tetanus-whole-cell-Pertussis-Haemophilus Influenzae Type b (DTPH) vaccines (administered: 1994-1997) and following Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP), vaccines in comparison to Thimerosal-free DTaP vaccines (administered: 1997-2000), was undertaken. RESULTS: Significantly increased adjusted (sex, age, vaccine type, vaccine manufacturer) risks of autism, speech disorders, mental retardation, personality disorders, thinking abnormalities, ataxia, and NDs in general, with minimal systematic error or confounding, were associated with TCV exposure. CONCLUSION: It is clear from the results of the present epidemiological study and other recently published data associating mercury exposure with childhood NDs, additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially from Thimerosal-containing vaccines.

Child, Preschool↗
PubMedDate not supplied

[Infant "starting formulas" are not all equal: comparative analysis of nutritional characteristics].

Infant formulas on the market today represent the only available alternative to breast milk for infants of those women who are unable to continue breastfeeding through the first year of life, and are planned to allow artificially fed infants for approaching the structural and functional effects observed in breastfed infants. Within this context, the functional outcome of the breastfed infant (particularly as far as growth and development) well represent the gold standard. For this purpose, the following compounds have been added to starting infant formulas (planned for the first six months of life, when human milk should represent the exclusive dietary source) in recent years: long-chain polyunsaturated fatty acids (LCPUFA), for brain composition and neurodevelopment, probiotics and prebiotics for the fecal flora and the local intestinal defense, and nucleotides for promoting the immune response. Changes in protein quantity and quality allow to balance the blood amino acids pattern (possibly relevant to the early stages of brain development for the neurotransmitter function) and reducing the protein intake could be important for the prevention of later overweight. Hydrolysed proteins may be relevant in the prevention of atopic disorders. Many trials have been published so far with short-term assessment, nevertheless, we need more data on the long-term follow-up of infants who were fed the new formulas to fully understand the role of these functional compounds on the neural performance, the prevention of overweight and obesity and the development of the immune-allergic pattern.

Carbohydrates↗
PubMedDate not supplied

[Disability in childhood. Care and professional training regarding particularly the problems currently seen in long-term control of newborns at risk].

Children with disability are a heterogeneous population distributed between complex conditions including physical disorders, psychomotor and neurodevelopment disorders, social role and school activities limitations. Prenatal, perinatal and neonatal diseases together with disabling chronic conditions may cause childhood disability. Data from literature show a prevalence of childhood disability ranging from 5 to 20% with a wide range of severity level. The social impact of childhood disability is extremely relevant. Children with disabilities frequently require health care services and special education. VLBW (very low birth weight infants, birth weight <1500 gr) have major disabilities (10-15%) while minor disabilities can be found in 20-25% of these subjects. The first step stays in medical prevention but also an oriented training toward these problems for doctors both in pre and post-graduate formation can play a significant role. Support of society in order to understand the complexity and heterogeneity of childhood disability, through social care services, is mandatory. These measures, apparently costly, if correctly done, will be helpful for both the individual subject and the whole society, through a reduction of the disability problems and the final economy cost impact.

Adolescent↗
PubMedDate not supplied

[Alcohol consumption, pregnancy and fetal alcohol syndrome: implications in public health and preventive strategies].

Alcohol consumption during pregnancy is a significant public health problem and is an established cause of serious birth defects and developmental delay collectively described as fetal alcohol syndrome (FAS). FAS is caused by congenital alcohol-induced damages and is a cause of mental retardation. It is characterised by facial abnormalities and growth deficiency. Infants affected by the syndrome show intellectual impairment, and difficulties in learning, memory, problem-solving, and attention as well as experiencing additional problems with mental health and social interactions. However, an absence of the characteristic facial defects and growth deficiency may result in a failure to identify children with prenatal alcohol exposure, which can further present as alcohol-related neurodevelopment disorder (ARND) or alcohol-related birth defects (ARBD). Estimates of prevalence of FAS in U.S.A. range between 0.3 to 2.2 per 1,000 live births, but much higher rates occurring in some communities. Harmonisation of the methodology used for epidemiological studies, with research activities that establishes real baseline prevalence of FAS and identification of women who are at highest risk of bearing a FAS-affected child, are an essential prerequisite to prevention. In addition, it is essential to assess different FAS preventive approaches through carefully controlled studies. Universal, selected, and indicated preventive strategies have been identified, targeting different kind of populations. Since FAS and other adverse effects of drinking during pregnancy are theoretically completely preventable, it is vital to make more efforts to improve the application of the most appropriate interventions. Although in Italy alcohol consumption has constantly increased, mainly amongst the young (including women of childbearing age), knowledge on FAS and alcohol-related effects is completely lacking. Because of the high cost for care of individuals with this syndrome, it is essential to apply appropriate interventions to prevent this problem.

Adult↗
PubMed2006

[Schizencephaly--clinical and radiological presentation of pediatric patients].

UNLABELLED: Schizencephaly is a rare central nervous system malformation. The anomaly is characterized by uni- or bilateral clefts in the brain's cerebral hemispheres. There are 2 types of the anomaly distinguished: type I ("closed lips") if there are fused clefts in cerebral mantle and type II ("open lips") if the clefts are separated. The etiology of this malformation is not clear; both environmental (intrauterine cytomegaloviral infection) and genetic risk factors are considered (mutations in EMX2, Lhx2 genes). The aim of the study was the analysis of clinical presentation, neurodevelopment progress and seizures in children with schizencephaly. MATERIAL AND METHODS: We examined 9 children (4 girls, 5 boys) at the age of 3 months to 11 years at the time of schizencephaly diagnosis. The neuroimaging (computed tomography--CT or/and magnetic resonance imaging--MRI) was performed in all of the patients. We found bilateral schizencephaly in 7 patients and unilateral in 2 of them; in 5 patients the brain anomalies other than schizencephaly were found. Epileptic seizures are present in 7 patients; in 2 of them the epilepsy is drug resistant. The development is delayed in all our patients, in spite of one. CONCLUSIONS: Schizencephaly is a severe brain malformation almost always leading to developmental delay and epilepsy. We did not found the correlation between the type of anomaly and clinical course, the degree of developmental delay and the severity of epilepsy in our group patients.

Cerebral Cortex↗
PubMed1991

Effects of prenatal cocaine exposure on perinatal morbidity and postnatal growth in the rabbit.

Prenatal cocaine (CC) exposure may result in increased fetal loss, growth retardation, altered neurodevelopment, and sudden infant death syndrome (SIDS). We sought to establish an animal model for prenatal cocaine exposure which (1) would allow us to distinguish the direct effects from the indirect and nutritional effects of the drug, and (2) might be used to address questions of cocaine's toxicity, specifically to the developing respiratory control system. The study design included 38 New Zealand White rabbit does among CC, pair-fed (PF), and free-fed (FF) groups. Miniosmotic pumps were implanted in each doe on day 10 of timed gestation providing continuous subcutaneous administration of either 30 mg/kg/day of cocaine HCl in H2O (CC) or sterile H2O alone (PF and FF). Mean (SEM) plasma cocaine concentration was 1.71 +/- 0.21 mumol/l (519.4 +/- 64.4 ng/ml). Pregnancy outcome compared for incidence of stillbirth, maternal death, spontaneous abortion, and gross malformation among 211 pups was significant only for increased stillbirths among CC pups (18%, p less than 0.04) as compared to PF (6%) and FF pups (7%). External and renal malformation and postnatal weight, crown-rump length, and snout-occiput head circumference for pups aged 4 and 5 days of age did not differ among groups. The direct effects of prenatal cocaine evaluated in our model do not reproduce the altered perinatal outcome observed among humans. However, our results do not determine if physiologic function has been altered. Investigation of the physiologic and pathologic abnormalities that are relevant to this human condition, specifically to the developing respiratory control system, should add clarity to the mechanism of action of cocaine during pregnancy.

Abortion, Spontaneous↗
PubMed1991

Treatment with methylazoxymethanol at different gestational days: physical, reflex development and spontaneous activity in the offspring.

Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational day 14, 15, 16, 17, 18 or 19 and offspring were tested for their physical development, reflex development and spontaneous activity. MAM treatment did not affect gestational and litter parameters at any of the time of administration studied. Treatment at gestational day 14 (GD14) had the most severe effect on functional neurodevelopment until weaning: righting reflex at surface, chimney test, horizontal wire test resulted altered. Administration at GD15, 16, 18, 19 did not affect the performance in these tests. Offspring treated at GD17 showed a delayed eye opening and an impaired performance in the horizontal wire test. When tested at 50 days of age on the rotarod, all the treated groups performed worse than controls with the exception of GD19 treated offspring. Administration at GD14 and GD15 resulted in increased spontaneous activity of the offspring at 21 days but not at 60 days of age. Different degrees of microencephaly were observed for all treated groups. The results indicate that alterations of physical and behavioral development induced by MAM treatment are dependent on the time of MAM administration, and specific behavioral tests are able to detect different abnormalities and differentiate among treatment groups. Some alterations observed in MAM rats undergo to adaptive changes during maturation of the CNS.

Animals↗
PubMed1991

Neurodevelopmental outcome of asymptomatic & symptomatic babies with neonatal hypoglycaemia.

A total of 107 babies with hypoglycaemia were studied over a period of 15 months. Symptomatic hypoglycaemia was found in 43 while it was asymptomatic in the others. Asymptomatic hypoglycaemia occurred at a relatively earlier post-natal age (4.5 +/- 2.2 h), as compared to symptomatic hypoglycemia (18.5 +/- 5.4 h, P less than 0.001). The mean blood glucose in hypoglycaemic babies with seizures was found to be significantly lower (P less than 0.001) when compared to those with other features as well as asymptomatic ones. Hypoglycaemia lasted for a significantly longer duration in symptomatic babies as compared to those without symptoms (P less than 0.001). On neurodevelopment follow up the mental developmental index (MDI) and the psychomotor developmental index (PDI) of symptomatic babies with seizures were significantly lower (P less than 0.001) as compared to those with other features of hypoglycaemia as well as asymptomatic babies. The neurodevelopmental status of babies with symptoms other than seizures was also significantly poorer (P less than 0.001), when compared to asymptomatic hypoglycaemic babies. The duration of hypoglycaemia was directly related to the MDI (r = -0.74, y = 102.5 - 0.69x) and PDI (r = -0.81, y = 105.6 - 0.86x). This study indicates that there is a need to identify babies vulnerable to symptomatic hypoglycaemia more precisely.

Humans↗
PubMed1990

Imaging procedures and developmental outcomes in the neonatal intensive care unit.

Behavioural and environmental modification techniques in the neonatal intensive care unit for oxygen-dependent premature infants with chronic lung disease have been shown to result in a decrease in the number of days of respirator support and number of days of supplemental oxygen therapy. Long-term neurodevelopment outcome was significantly better for infants in the experimental therapy group who received specialized environmental modification to decrease stressful stimuli. We present results of cranial ultrasound and chest radiograph studies in this very high-risk population and suggest that such studies represent additional stressful stimuli that should be scheduled with consideration of an overall behavioral infant care plan.

Bronchopulmonary Dysplasia↗
PubMed1990

Polycythemia in the newborn: do asymptomatic babies need exchange transfusion?

A total of 2288 infants were screened for hematocrit over a period of 15 months. Polycythemia was diagnosed in 27 cases (1.2%). Preterm and term babies had more or less equal risk to develop polycythemia (1.5% and 1.1% respectively) while postterm infants had at least three times increased risk (3.4%) when compared to their term counterparts. Large-for-dates (LFDs) and small-for-dates (SFDs) infants had increased risk of manifesting polycythemia which was nearly four times (2.2%) and twenty-five times (13.2%) respectively, as compared to appropriate-for-dates (AFDs) babies (0.5%). About one-third of polycythemic infants had one or more symptoms. The most common symptoms observed was jitteriness (25.9%) followed by respiratory distress (14.8%) and lethargy (11.1%). The mean (+/- SD) hematocrit of symptomatic newborns (76.0 +/- 4.04) was found to be significantly higher (p less than 0.001) as compared to asymptomatic babies (70.84 +/- 2.73). Partial exchange transfusion with plasma was performed in all the symptomatic cases within 8 hours of onset of symptoms. No such intervention was performed in asymptomatic cases. On neurodevelopment follow-up, the development indices (MDI and PDI) of both asymptomatic and symptomatic cases were found to be comparable.

Growth↗
PubMed1990

[A study of the sequelae of perinatal hypoxia and convulsions in full-term newborn infants].

Perinatal hypoxia may result in neuromotor handicaps. The occurrence of convulsions after perinatal hypoxia is regarded as a bad prognostic sign. Thirty-two full-term babies with perinatal hypoxia were studied retrospectively. Post-hypoxic convulsions were seen in 20 newborns. In 26 out of 29 survivors follow-up assessments were made between 2 months and 2 years of age. Severe neuromotor abnormalities were demonstrated in 10 out of 19 patients with post-hypoxic convulsions, whereas no abnormalities were found in 7 patients without convulsions (p = 0.016, Fisher exact test). Although post-hypoxic convulsions are a bad prognostic sign, a number of infants with convulsions appear to develop normally. Further research on prognostic factors concerning neurodevelopment after perinatal hypoxia and convulsions appears indicated.

Child Development↗
PubMed1989

Antenatal steroid therapy and 5-year outcome of extremely low birth weight infants.

Over a 63-month period beginning January 1, 1977, 258 infants with birth weights of 500-999 g were born alive at one tertiary perinatal center; 170 were offered full intensive care. The mothers of 67 (39.4%) of these 170 infants had been given betamethasone antenatally to accelerate fetal lung maturation. Of the 67 infants exposed to steroids antenatally, 46 (68.7%) survived their primary hospitalization, compared with 43 (41.7%) of the 103 infants who had not been exposed to steroids. This difference is highly significant (chi 2 = 10.7; P less than .005) but is biased because infants in the steroid group had a better prognosis. After adjustment for discrepancies in birth weight and gestational age and other confounding obstetric variables, survival in the steroid group remained substantially higher (relative odds of survival 1.85, 95% confidence intervals 1.16-2.86; P = .006). The improvements in survival were not at the expense of increased rates of chronic ill health or impairments of growth neurodevelopment up to at least 5 years of age. For extremely immature and extremely low birth weight infants, steroids are rarely contraindicated on fetal grounds.

Betamethasone↗
PubMed1989

Severity of necrotizing enterocolitis: influence on outcome at 2 years of age.

The long-term outcome of very low birth weight (VLBW) infants with necrotizing enterocolitis has been reported to be similar to that of other VLBW infants. To examine the influence of disease severity on outcome, the growth and neurodevelopment of survivors of necrotizing enterocolitis were evaluated when the babies were 20 months' corrected age. Between 1975 and 1983, 1506 VLBW infants were admitted to the hospital, and necrotizing enterocolitis developed in 84 (5.6%). Forty infants (48%) survived to be 20 months' corrected age, and complete follow-up data were available for 36. Survivors were classified by modified Bell's criteria into four groups by increasing severity of disease; 13 had mild necrotizing enterocolitis (stage IIA, IIB), and 23 had severe necrotizing enterocolitis (stage IIIA, IIIB). The 36 survivors were compared with 766 surviving VLBW infants without necrotizing enterocolitis. There were no perinatal or socioeconomic differences between groups. Compared with infants with stage II necrotizing enterocolitis at 20 months, infants with stage III necrotizing enterocolitis had a higher rate of subnormal body weight (39% vs 15%) and subnormal head circumference (30% vs 0%). Thirty-three percent of necrotizing enterocolitis survivors had significant neurodevelopmental impairment; the majority of impaired infants (10 of 12) were survivors of stage III necrotizing enterocolitis. These findings highlight the importance of continued evaluations for medical and neurodevelopmental sequelae.

Child Development↗
PubMed1985

Regulation of cholinergic development by target contact.

Avian ciliary ganglion neurons in cell culture have been used as a model neuronal system to examine the developmental role of direct contact with an appropriate target tissue. Live myotubes, which are immediately innervated, and their membrane remnants, on which neurons form terminal structures, were both found to stimulate or accelerate the acquisition or retention of important parameters of neuronal function. Contact with the target membrane supports survival, aids retention of active nicotinic receptors to acetylcholine, and accelerates the acquisition of adult transmitter synthetic capacity. These results emphasize the multifaceted nature of neurodevelopment, with soluble protein factors, membrane-bound elements, and other functional events all acting in concert in the embryonic nervous system.

Acetylcholine↗
PubMed1988

The importance of regressive changes in the development of the nervous system: towards a neurobiological theory of child development.

In this paper we propose that theories of early personality development be revised to consider knowledge of neurodevelopment. Research findings are reviewed that have established the presence of regressive changes in the normal development of the brain. These regressive changes, consisting of neuronal death and process and synapse elimination, are theoretically linked to three precursors of personality: sex differences, temperamental traits and perceptual-motor coordination. Evidence supporting these hypotheses is provided from studies examining how the effects of genetic, environmental, and experiential factors on brain development may determine the development of these personality features.

Animals↗
PubMed1984

Two year longitudinal followup of premature infants weighing less than or equal to 1,200 grams at birth: sequelae of intracranial hemorrhage.

Intracranial hemorrhage (ICH) is a major problem for the premature infant, occurring in more than one-third of surviving infants weighing less than or equal to 1,500 g at birth. The literature on perinatal ICH, as it relates to neurodevelopment outcome, is briefly reviewed, and preliminary results from our two-year followup of 75 less than or equal to 1,200-g infants are summarized. An analysis of pathophysiology, diagnosis, classification, and followup indicates that risk for ICH and its sequelae increases as gestational age and birth weight decrease. Hydrocephalus apparently no longer presents significant risk beyond that conveyed by the original hemorrhage. However, persistent posthemorrhagic ventriculomegaly and/or periventricular abnormalities serve as significant "markers" of risk for neuromotor delay through two years of age. In contrast, recovery of normal ventricular morphology by term gestational age apparently indexes a degree of recovery from ICH and predicts a more normal developmental outcome through the first two postnatal years.

Birth Weight↗
PubMed1995

Controlled trial of dexamethasone in neonatal chronic lung disease: a 3-year follow-up.

OBJECTIVE: We compared the effects of a policy of neonatal steroid administration versus placebo for babies chronically dependent on supplemental oxygen in terms of long-term health and development, judged at 3 years of age. DESIGN: Double-blind randomized controlled trial. SETTING: Thirty-one centers in the United Kingdom, Ireland, Belgium, Germany, Canada, and the United States. PATIENTS: Babies who were chronically dependent on supplemental oxygen between 2 and 12 weeks of age were recruited to the trial between 1986 and 1989. Sixty-two children were known to have died, 23 before discharge from the hospital and 10 afterward in the active group, compared with 25 and 4, respectively, in the placebo group. Information was available for 209 of the 212 eligible for follow-up (99%). INTERVENTIONS: A 1-week course of active dexamethasone phosphate 0.6 mg/kg/d (dexamethasone base 0.5 mg/kg/d) or saline placebo was given intravenously (or orally, if no intravenous line). There was an option to give a second tapering 9-day course if relapse occurred after initial improvement. OUTCOME MEASURES: Information about respiratory problems, growth, neurodevelopment and disability, infection, and health service use when the children were 3 years old was ascertained from questionnaires to general practitioners, health visitors, and parents (and occasionally pediatricians). RESULTS: About half the children in both groups had been admitted to the hospital for respiratory problems, with more in the active than the placebo group having at least five outpatient consultations for these problems over the 3 years. Overall, the children were below average in height, weight, and head circumference. About one fifth had cerebral palsy, 8% some visual loss, and 16% hearing loss; 18% needed or were anticipated to need special schooling. There were no clear differences between the randomized groups. These overall conclusions were not altered by any of the prespecified secondary analyses. CONCLUSIONS: Despite early benefits, there were no clear effects at 3 years of age. As 40% of the placebo group eventually received open steroids, even a trial of this size has limited statistical power to detect a moderate effect of the policy. Regardless of random allocation, overall morbidity was high, confirming that babies with protracted dependence on supplemental oxygen are at high risk of childhood disability and poor health.

Chronic Disease↗