Jag Ahluwalia

Sex differences in human neonatal social perception

Sexual dimorphism in sociability has been documented in humans. The present study aimed to ascertain whether the sexual dimorphism is a result of biological or socio-cultural differences between the two sexes. 102 human neonates, who by definition have not yet been influenced by social and cultural factors, were tested to see if there was a difference in looking time at a face (social object) and a mobile (physical-mechanical object). Results showed that the male infants showed a stronger interest in the physical-mechanical mobile while the female infants showed a stronger interest in the face. The results of this research clearly demonstrate that sex differences are in part biological in origin.

Is there an innate gaze module? Evidence from human neonates

Abstract Evidence from various fields that suggests humans have a specialized neural system dedicated to perceiving another’s eyes and detecting the direction in which they are gazing. The evidence is, however, inconclusive about whether this system is already operating in neonates. 105 neonates were presented with two photographs separately. One was a female adult face with the eyes open and the other was the same face with the eyes closed. Results indicated that the neonates spent significantly more time looking at the photograph with the eyes open than at the photograph with the eyes closed. This result may reflect that neonates have a special neural mechanism that detects eye-like stimuli in the environment and orients attention towards them. This new visual preference in infants warrants further research.

Early Insulin Therapy in Very-Low-Birth-Weight Infants

BACKGROUND Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates. METHODS In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm. RESULTS As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04). CONCLUSIONS Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)

The continuous glucose monitoring sensor in neonatal intensive care

Objective: To determine the feasibility of continuous glucose monitoring in the very low birthweight baby requiring intensive care, as these infants are known to be at high risk of abnormalities of glucose control. Method: Sixteen babies were studied from within 24 hours of delivery and for up to seven days. Results: The subcutaneous glucose sensors were well tolerated and readings were comparable to those on near patient whole blood monitoring devices. Conclusion: Continuous glucose monitoring is practical in neonates, giving detailed information about glucose control.

Prevalence and Determinants of Hyperglycemia in Very Low Birth Weight Infants: Cohort Analyses of the NIRTURE Study

OBJECTIVES To investigate the prevalence and determinants of hyperglycemia in the preterm population, as part of the Neonatal Insulin Therapy in Europe (NIRTURE) Trial. STUDY DESIGN We conducted prospective cohort analyses of continuous glucose monitoring data from control infants participating in an international randomized controlled trial. Data were collected from 188 very low birth weight infants (<1500 g). RESULTS In the first week of life, 80% of infants had evidence of glucose levels >8 mmol/L, and 32% had glucose levels >10 mmol/L >10% of the time. Independent risk factors for hyperglycemia included increasing prematurity, small size at birth, use of inotropes, lipid infusions, and sepsis. There was a lack of association between rate of dextrose infused and risk of hyperglycemia. CONCLUSION The prevalence of hyperglycemia in the very low birth weight infant is high, with marked variability in prevalence between infants, not simply related to rates of glucose infused, but to other potentially modifiable risk factors.

Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age

BackgroundStudies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children.Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old.FindingfT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores.ConclusionsThese preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life.

A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe)

BackgroundStudies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and β cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer β cells are linked to risk of type 2 diabetes later in life.MethodsA multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4–8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth.Trial RegistrationCurrent Controlled Trials ISRCTN78428828. EUDRACT Number 2004-002170-34

Can asperger syndrome be diagnosed at 26 months old? A genetic high-risk single-case study

Asperger syndrome, a heritable condition entailing empathy deficits together with unusually narrow interests in individuals of normal or even above-average intelligence, was recognized only recently. Here we report the first-ever prospective study of a child born to two adults with a formal diagnosis of Asperger syndrome. The childs parents are both scientists (a mathematician and a chemist). The aim of study 1 was to test if the child also developed Asperger syndrome, given the heritability of the condition, and if Asperger syndrome can be detected at 26 months. At 18 months, the child was given the Checklist for Autism in Toddlers, and at 26 months, she was assessed diagnostically for autism spectrum conditions using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observational Scale. The child failed the Checklist for Autism in Toddlers at 18 months and met the criteria for Asperger syndrome at 26 months. This single case is consistent with the hypersystemizing, assortative mating theory of autism. This theory requires further testing with large samples. This study also demonstrates that Asperger syndrome can be diagnosed by age 26 months. The aim of study 2 was to test if dyadic eye contact in infancy is intact in a child later diagnosed with Asperger syndrome. The same childs eye contact was measured at three time points (3, 6, and 9 months) over her first year of life and compared with that of age-matched controls. Although the child had low rates of eye contact at 6 months, it was within the normal range at all three points in the first year of life. We conclude that low levels of eye contact are not predictive of later development of Asperger syndrome. (J Child Neurol 2006; 21: 351—356; DOI 10.2310/7010.2006.00072).

Relationship between insulin-like growth factor I levels, early insulin treatment, and clinical outcomes of very low birth weight infants.

OBJECTIVES Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 μg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

Should newborn infants be excluded from multiple research studies

1The website of the British Association of Perinatal Medicine lists 20 ongoing clinical trials in which many units in Europe will be participating. 2 In a typical subspecialty neonatal unit in the UK a pre term infant might be eligible to participate in six research studies, ranging from international, multi centre, randomised controlled trials to local, unit-based observational studies. The scientifi c and ethical implications of recruiting patients to more than one clinical trial or research study are unclear but are particularly important in perinatal medicine. We are aware of signifi cant diff erences in attitudes across Europe. The Association of British Pharmaceutical Industries gives guidance, based on expert opinion, that there should be a gap of at least 3 months between an individual’s (healthy volunteer) involvement in medicinal trials to allow for wash out of drug eff ects. 3