Early androgen influences on human neural and behavioural development

Gonadal hormones, particularly androgens, influence sexual differentiation of the body, as well as the brain and behaviour. Antenatal exposure to atypical hormone environments leads to alterations in human behaviours that show sex differences. These include childhood play, sexual orientation, gender identity, and personality characteristics, such as empathy and aggression. Individual variability among healthy children in antenatal hormone exposure show similar relationships to individual variability in postnatal behaviour. As in studies of atypical exposure, higher levels of androgen predict more male-typical, and less female-typical, behaviour. Hormone-induced alterations in brain development are thought to underlie these behavioural outcomes, although there is little information on specific neural differences associated with early hormone differences. Notable, however, is evidence relating early androgen exposure to activation of the medial amygdaloid nucleus in women. Other emerging research areas include the role of neonatal hormones in infant development and interactions between hormone-induced predispositions and postnatal experience in producing behavioural outcomes.     

Pregnancy-induced hypertension,antihypertensive drugs and the development of fetal behavioural states

In 21 pregnancies complicated by pregnancy-induced hypertension (PIH) which was treated by antihypertensive drugs (labetalol, nifedipine), fetal behavioural recordings (quiet state, C1F; active state, C2F; no coincidence, NOC) and Doppler measurements of blood flow velocity in the umbilical artery (UA) (resistance index, RI) were made on two occasions (27–32 and 33–36 weeks of gestation). Data were compared to those of a control group of normally grown fetuses (n = 96); in 15 cases we were able to match fetuses from the study group for age (±1 week) and weight (±150 g) at birth with fetales from a control group. It was the aim of this study to investigate if there are disturbances in the development of fetal behavioural states and if possible disturbances are due to poor fetal growth or to antihypertensive therapy. Our results show that in PIH treated by antihypertensive drugs, there are disturbances in the development of fetal behavioural states with higher percentages of NOC and C1F, lower percentages of C2F, and higher UA RI values. These disturbances are mainly due to coexisting placental impairment and poor fetal growth rather than to nifedipine or labetalol therapy, although these drugs may cause some redistribution of states.     

Glucocorticoids and growth in asthmatic children

The effects of asthma and oral and inhaled glucocorticoid therapy on growth in children are reviewed. Previous reports have shown that asthma itself may delay the onset of puberty, an effect which may masquerade as growth suppression. Oral glucocorticoids appear to impair growth; however, lower doses and alternate-day therapy may have less risk of this effect. While a controversial topic, inhaled glucocorticoids in lower doses appear to be associated with a small risk of adverse effects on growth. Minimal data are available for higher doses. Knemometry, a relatively new technique used for measuring small changes in growth, has detected short-term effects with both oral and inhaled glucocorticoids therapy. However, a number of limitations are associated with short-term growth studies. Clinicians should be aware of the potential for growth impairment with glucocorticoid therapy so adequate monitoring can be undertaken and appropriate intervention introduced when deemed necessary.     

Minor neurological dysfunction and behavioural development. A report from the Groningen Perinatal Project

In a follow-up study of 230 children a statistically significant relation was found between the neonatal neurological diagnosis and the presence of minor neurological dysfunctions at the age of 6 years: of 167 normal newborns, 7% turned out to have MND at follow-up versus 21% of 63 (mildly) abnormal neonates. Interval complications occurred especially in the latter group of MND children. Their presence may have hampered recovery. Both follow-up and neonatal neurological diagnoses were in a varying degree related to undesired behaviour as reported by parents and teachers, such as 'clumsy', 'difficult to handle', 'hyperactive', 'irritable' and 'temper tantrums'. However, only to a limited extent the variance of the behaviour was explained by the neurological findings. It was concluded that, although the neurological condition of a child may determine his vulnerability for environmental influence to a certain extent, the contribution of both sex and environment on behavioural development is preponderant.     

The influence of piglet birth weight on physical and behavioural development in early life

The objective of this study was to determine whether body weight at birth influences the physical and behavioural development of the neonatal pig. Sixteen sows and their litters were randomly allocated into four treatment groups. From the normal distribution curve of their birth weight, piglets were sub-divided into three groups: (1) low (<10th percentile) (2) normal (10-90th percentile) and (3) high (>90th percentile).To assess behavioural development, each litter was exposed to a ball placed in the creep area for a period of 1,800 s, and evaluated once over a 3-day period starting on either 5, 7, 14 or 21 days of postnatal life. Their response to, and interaction with, an object was used to calculate a numerical index of piglet behavioural development. Teat order was calculated following observations during consecutive suckling on days 11, 13 and 15 of life, and dominance hierarchy was assessed on day 12, 14 and 16. Individual body weight was recorded on days 0, 5, 7, 14 and 21 of postnatal life. Statistical differences between groups were analysed using general linear model, analysis of variance. Regression analyses were used to determine relationships between physical and behavioural development with teat order and dominance. There was a significant (p < 0.001) relationship between birth weight, growth performance and behavioural development. Behavioural developmental index (BDI) significantly improved (p < 0.001) with age and was also influenced by the day on which the ball was introduced (p < 0.01). Body weight on day 1 of the test was significantly (p < 0.001) correlated to BDI and age at test. Piglets demonstrating compensatory growth were more dominant and exhibited an improved behavioural developmental score than their slower growing littermates. In conclusion, compromised growth in utero can have a detrimental effect on the physical and behavioural development of the neonate. Animals with an enhanced developmental index in conjunction with a higher dominance value exhibited a improved neonatal growth performance.     

Parents' perception of mental development and behavioural problems in 8 to 9-year-old children

A slow maturational rate may be an underlying antecedent of a psychiatric disorder. If this is correct, differences in behavioural problems could be related to the maturity level in children of the same chronological age. The aim of the study was to compare the parents' perceptions and assessments of their children's maturational status and behavioural problems. A population based on a nationwide sample from the Swedish twin-register of 8 to 9-y-old children (n = 1079) was used. The parents completed a questionnaire including their views on their child's maturity level, the Swedish version of the Child Behaviour Checklist (CBCL) and an Attention Deficit Hyperactivity Disorder (ADHD) checklist based on the DSM-III-R criteria. Multivariate analyses showed a statistically significant relationship between immaturity reported by the parents and several behavioural problems reported on the CBCL: somatic complaints, anxious and depressed, social problems, thought problems, attention problems, behaviour problems and aggressive behaviour. There was also a statistically significant relationship between the maturity factor and the CBCL grouping of syndromes (internalizing, externalizing, total behaviour problems score) as well as between the maturity factor and ADHD. Conclusion: We conclude that at least from the parents' point of view the behaviour problems in their children may be related to maturity.     

Glucocorticoids and the development of neuronal function: effects of prenatal dexamethasone exposure on central noradrenergic activity.

Although glucocorticoids slow the development of most cell types, they have been hypothesized to promote the differentiation of catecholaminergic cells. In the current study, pregnant rats were given dexamethasone on gestational days 17, 18 and 19, and the functional state of noradrenergic synaptic activity was assessed throughout postnatal development by measurements of transmitter levels and turnover, and receptor binding capabilities. Despite growth inhibition caused by dexamethasone, the steroid treatment had little or no effect on transmitter levels or receptor binding and accelerated the maturation of norepinephrine turnover in a regionally selective manner. Effects were most notable in the midbrain and brainstem, where turnover rose to maximum levels 1-2 weeks in advance of controls. Turnover also leveled off prematurely in the dexamethasone group, leading to deficits in the postweaning period and into young adulthood. Although similar patterns were obtained in other, later-developing regions, the effects were less consistent and robust; the smaller effects also extended to dopamine turnover. These results suggest that glucocorticoids have a specific promotional effect on the development of central catecholaminergic activity and that administration of exogenous steroids during critical periods of development can lead to lasting functional abnormalities.     

Glucocorticoids,inflammation and the perinatal lung

Many women delivering preterm infants at less than 30 weeks gestation have subclinical chorioamnionitis. Based on current guidelines, maternal glucocorticoid treatment is given to induce lung maturation. Fetal exposure to proinflammation can cause acute and chronic injury, but inflammation also can induce fetal lung maturation. Both antenatal glucocorticoids and inflammation modulate lung development, by inducing the surfactant system, inducing structural maturation, and inhibiting alveolarization. The opportunities for the future are to develop new safer strategies to mature the preterm foetus, and the risks are potential adverse interactions of repetitive glucocorticoid exposures and unrecognized fetal exposure to inflammation.     

Body measurements, neurological and behavioural development in six-year-old children born preterm and/or small-for-gestational-age

In three groups of low birth weight (LBW) infants: full term, small-for-gestational-age (FT-SGA, N = 142); preterm, appropriate-for-gestational-age (PT-AGA, N = 47); preterm, small-for-gestational-age (PT-SGA, N = 20); and a reference group of FT-AGA infants (N = 185) the relationship between body weight, body length and head circumference and the presence of minor neurological dysfunction (MND) was studied. Non-caucasian and handicapped children were excluded from the analysis. Data were collected on behaviour and school achievement. The parameters of physical growth in the three LBW groups were reduced significantly compared to the FT-AGA group. In both preterms and full-terms body measurements were related to weight at term age; in the preterm groups no relation with gestational age at birth was found. MND was not related to body weight or length. In the group of FT severely growth retarded infants a relation was found between a skull circumference below the third centile and the presence of MND. Body measurements, behaviour at home and at school and school achievement were not related. The significance of severe intrauterine growth retardation for developmental disorders is emphasized. The data suggest a different aetiology and clinical significance of small head size for AGA and SGA born children.     

Neurodevelopmental and behavioural paediatrics

One of the notable shifts in Paediatrics across the last 50 years has been towards disorders that are chronic and qualitative in nature. In addition to physical health, these impact on childhood development, behaviour and wellbeing. Understanding and management of these problems extends the traditional biological toolkit of paediatrics into the complexities of uncertainties of psychological and social context. In Australasia, the profession has responded with the development of Community Paediatrics as a recognised sub‐specialty, of which Neurodevelopmental and Behavioural Paediatrics is an important component. These developments are reviewed along with consideration of future challenges for this field of health care.     

Characteristics in the development of symptoms in the in-patient treatment of aggressive behavioural disorders

The symptom development within therapy of 16 juvenile patients is analysed starting from an integrated cognitive therapeutical attempt at changing aggressive behaviour. By means of "event sampling" of aggressive escalations the changes in the frequent occurrence of symptoms on the basis of the starting data of the first therapy phases were compared with data from the last therapy phases, where various change criteria were taken as a basis. In this case the symptom improvement clearly outweighs the deteriorations in each case. A parameter-free cluster analysis of the respective symptom courses allows the hypothesis, that an intensive aggressiveness of longer duration at the beginning promises a more favourable entire development in therapy, to appear justified.     

Fetal behavioural states and controlled sound stimulation

The aim of this study was to investigate responses of human fetuses near term (37-42 wks) (increase/decrease of fetal heart rate and/or fetal motility) to acoustic stimuli. The study group consisted of 43 patients and the control group of 27 patients. Polygraphic recordings of 5 different fetal variables were carried out synchronously for the categorization of the actual fetal behavioural state according to Nijhuis et al. (Nijhuis, J.G., Prechtl, H.F.R., Martin, C.B., Jr. and Bots, R.S.A.M. (1982): Early Hum. Dev., 6, 177-195). Controlled acoustic stimulation was performed either with sine wave tone (2 kHz, 120 dB and 5 s duration) or modulated sine wave tone (0.5-2 kHz, 'sawtooth' modulation, 120 dB and 5 s duration). An additional group of patients received 'sham' stimulation. Overall 84 acoustic stimulations have been carried out. In 26 out of 84 stimulations (30%) a fetal response could be observed within 5 s after acoustic stimulation. In general, there were far fewer fetal responses in sleep states than in states of wakefulness. Whereas in state 1 F only 1 out of 28 acoustic stimulations was followed by an immediate fetal response, more responses were observed in state 2 F. An obvious increase in fetal reactivity to acoustic stimulation was noted in states of wakefulness (states 3 F and 4 F). Comparison between the true and sham stimulations revealed a relatively high level of spontaneous fetal activity (high variation of fetal heart rate and fetal motility) present in states 2 F and 4 F. This must be taken into account in all assessments of fetal responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cognitive and behavioural concerns in epileptic children

Cognitive performance in an epileptic child has been a difficult issue to predict in day-to-day clinical practice. Several observations made in early and later part of this century do not provide uniform and convincing answer to this issue. Recent trends in research however, have identified certain variables that are shown to be associated with cognitive decline in epileptic children. Together with associated behavioural problems, the resultant school difficulty is the essence of this concern for the parents. The variables related to cognitive deterioration as identified by several studies include underlying brain pathology (symptomatic epilepsy), early age of onset of seizure, severity and intractability of seizure, repeated head trauma, an episode of status epilepticus, presence of interictal subclinical EEG discharge, adverse psychosocial factor and antiepileptic drug (AED). Association of these variables in a given case cannot only predict adverse cognition outcome but also a preventive management package can be planned aiming at avoiding or minimizing these high risk variables.