Embryonic disruption of the candidate dyslexia susceptibility gene homolog Kiaa0319-like results in neuronal migration disorders.

Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l small hairpin RNA (shRNA), (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA+KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). Mothers were injected with 5-bromo-2-deoxyuridine (BrdU) at either E13.5, E15.5, or E17.5. Disruption of Kiaa0319l function (by knockdown, overexpression, or rescue) resulted in the formation of large nodular periventricular heterotopia in approximately 25% of the rats, which can be seen as early as postnatal day 1. Only a small subset of heterotopic neurons had been transfected, indicating non-cell autonomous effects of the transfection. Most heterotopic neurons were generated in mid- to late-gestation, and laminar markers suggest that they were destined for upper cortical laminae. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminae. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia.

Sudden, unexpected and unexplained early neonatal deaths in the North of England.

Early neonatal sudden unexpected unexplained deaths (for which we use the term ENSUD) have not been subject to detailed study. The authors investigated the incidence from 1983 to 2007 in the population of the North East of England and North Cumbria. The authors found 30 cases of unexplained ENSUD, giving an overall rate of 0.35/10 000 live births, with no significant change in incidence over this time, and they identified a further 19 deaths of abandoned babies. The authors conclude that unexplained ENSUD is even more rare than has been appreciated and its incidence has not been altered by the considerable changes in maternity care over the last 25 years.

Mortality of twin and singleton livebirths under 30 weeks' gestation: a population-based study.

OBJECTIVE: To determine the mortality rates of liveborn twins compared with singletons of less than 30 weeks' gestation in relation to gestational age, mode of delivery and year of birth in a geographically defined population. STUDY DESIGN: Comparison of early neonatal, late neonatal and infant death rates in 479 twin babies and 1538 singletons, liveborn between 23 and 29 completed weeks of gestation in the north of England over two epochs, 1998-2001 and 2002-5. RESULTS: Twins and singletons had similar mortality rates except at the extreme of gestation (23-25 weeks) where twins had higher infant mortality (OR 2.04, 95% CI 1.37 to 3.02). This higher rate was attributable to early and late neonatal deaths (OR 1.86, 95% CI 1.28 to 2.72, and 2.11, 95% CI 1.13-3.94, respectively). When analysed in two epochs, the excess mortality was confined to babies born in 1998-2001. There was no effect of gender or chorionicity. CONCLUSIONS: The excess mortality among twins of less than 30 weeks' gestation was confined to neonatal deaths in babies of 25 weeks or less, and to the earlier epoch (1998-2001). In the modern era, there appears to be no excess mortality in neonates less than 30 weeks' gestation when compared with singletons.

Nursing workload in UK tertiary neonatal units.

BACKGROUND: Neonatal intensive care requires adequate numbers of trained neonatal nurses to provide safe, effective care, but existing research into the relationship between nurse numbers and the care needs of babies is over 10 years old. Since then, the preterm population and treatment practices have changed considerably. AIMS: To validate the dependency categories of the British Association of Perinatal Medicine (BAPM, 2001) and to revalidate the Northern Region categories (NR, 1993) in relation to contemporary nursing workload. SETTING: Three tertiary neonatal intensive care services in England. METHODS: Nursing activity around each baby was captured every 10 min by direct observations by trained observers. Time spent on each nursing activity was related to the baby's dependency category and the nurse's grade. RESULTS: Both scales detected differences between categories. Discrimination between individual categories was improved when nasal continuous positive airway pressure (nCPAP) was distinguished from ventilation and combined with BAPM2/NRA. On this revised four-point scale, babies in BAPM1/NRA occupied nursing time for a median of 56 min per hour (IQR 48-70), those on nCPAP or in BAPM2/NRB for 36 min, (27-42), those in BAPM3/NRC for 20-22 min (15-33) and those in BAPM4/NRD for 31-32 min (24-36). The NR scale was easier to apply and had greater interobserver agreement (98.5%) than the BAPM scale (93%). All categories attracted more time compared to 1993. CONCLUSIONS: Both scales predict average nursing workload. A revised categorisation which separates nCPAP from ventilation is more robust and practical. Nursing time attracted in all categories has increased since 1993.

The contribution of late termination of pregnancy to stillbirth rates in Northern England, 1994-2005.

The impact of late terminations (> or = 24 weeks) on the overall stillbirth rate was determined for the 12-year period from 1994 to 2005 using data collected by the Regional Maternity Survey Office in the north of England. It is a legal requirement to register late terminations, and this may lead to an overestimation of the true stillbirth rate. In our region, terminations resulting in stillbirth increased the registered stillbirth rate by nearly 10%. The impact remained stable for the period 1998-2005. This suggests that the failure of the national (and regional) stillbirth rate to decline in recent years is not due to an increase in late terminations.

Repeat testing for congenital hypothyroidism in preterm infants is unnecessary with an appropriate thyroid stimulating hormone threshold.

BACKGROUND: Revised UK neonatal screening guidelines recommend that a second blood sample for assay of thyroid stimulating hormone (TSH) be taken when preterm infants reach a postmenstrual age of 36 weeks. OBJECTIVE: To examine the results of a regional screening programme to see whether a rise in TSH concentration was observed in some preterm infants between the first sample taken around 5 days after delivery and the second sample taken at around 36 weeks. METHODS: Whole-blood TSH concentrations in preterm infants born over a 2-year period (April 2005 to March 2007) were assessed, and the number of infants in whom there was a fall or rise to values below or above the local screening threshold (6 mU/l) was determined. RESULTS: Baseline TSH samples were obtained from 2238 preterm infants (median gestational age 32 weeks, range 21-35) with second samples obtained from 2039 (median gestational 32 weeks, range 23-35). In 19 infants, TSH concentrations fell from above to below the screening threshold, and in five infants values rose from below the screening threshold to 6-10 mU/l. However, TSH concentrations fell to <6 mU/l on a further blood spot in four of these infants, and the remaining infant had a serum TSH of 6.8 mU/l. Three infants had raised TSH concentrations on both occasions with unequivocal hypothyroidism (serum TSH >80 mU/l). The initial TSH concentration in one of these infants was 6-10 mU/l. CONCLUSIONS: No infant with a normal TSH concentration on first sampling had a TSH concentration that rose above 10 mU/l on second sampling, and no infants with a normal TSH concentration on first screening are receiving long-term thyroxine treatment. This study suggests that a second sample may not be necessary with a screening threshold of 6 mU/l.

Randomised trial of infant sleep location on the postnatal ward.

OBJECTIVE: To determine whether postnatal mother-infant sleep proximity affects breastfeeding initiation and infant safety. DESIGN: Randomised non-blinded trial analysed by intention to treat. SETTING: Postnatal wards of the Royal Victoria Hospital (RVI), Newcastle upon Tyne, UK. PARTICIPANTS: 64 newly delivered mother-infant dyads with a prenatal intention to breastfeed (vaginal deliveries, no intramuscular or intravenous opiate analgesics taken in the preceding 24 h). INTERVENTION: Infants were randomly allocated to one of three sleep conditions: baby in mother's bed with cot-side; baby in side-car crib attached to mother's bed; and baby in stand-alone cot adjacent to mother's bed. MAIN OUTCOME MEASURES: Breastfeeding frequency and infant safety observed via night-time video recordings. RESULTS: During standardised 4-h observation periods, bed and side-car crib infants breastfed more frequently than stand-alone cot infants (mean difference (95% confidence interval (CI)): bed v stand-alone cot = 2.56 (0.72 to 4.41); side-car crib v stand-alone cot = 2.52 (0.87 to 4.17); bed v side-car crib = 0.04 (-2.10 to 2.18)). No infant experienced adverse events; however, bed infants were more frequently considered to be in potentially adverse situations (mean difference (95% CI): bed v stand-alone cot = 0.13 (0.03 to 0.23); side-car crib v stand-alone cot = 0.04 (-0.03 to 0.12); bed v side-car crib = 0.09 (-0.03-0.21)). No differences were observed in duration of maternal or infant sleep, frequency or duration of assistance provided by staff, or maternal rating of postnatal satisfaction. CONCLUSION: Suckling frequency in the early postpartum period is a well-known predictor of successful breastfeeding initiation. Newborn babies sleeping in close proximity to their mothers (bedding-in) facilitates frequent feeding in comparison with rooming-in. None of the three sleep conditions was associated with adverse events, although infrequent, potential risks may have occurred in the bed group. Side-car cribs are effective in enhancing breastfeeding initiation and preserving infant safety in the postnatal ward.

Evaluation of advanced neonatal nurse practitioners: confidential enquiry into the management of sentinel cases.

OBJECTIVE: To evaluate the quality of the neonatal care delivered by an advanced neonatal nurse practitioner led service at Ashington Hospital, Northumberland. SETTING: Maternity service with no resident paediatric medical input. DESIGN: Comparison of quality measures on sentinel cases with five comparator hospitals using modified confidential enquiry. RESULTS: On six out of seven dimensions, the neonatal nurse practitioner service performed better than the average of the five comparator hospitals, and overall ranked second. CONCLUSION: Good quality neonatal care can be delivered by advanced neonatal nurse practitioners alone, without the support of resident junior paediatricians.

Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds.

The definition of clinically significant hypoglycemia remains one of the most confused and contentious issues in contemporary neonatology. In this article, some of the reasons for these contentions are discussed. Pragmatic recommendations for operational thresholds, ie, blood glucose levels at which clinical interventions should be considered, are offered in light of current knowledge to aid health care providers in neonatal medicine. Future areas of research to resolve some of these issues are also presented.

Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at 25-29 weeks' gestation: a randomised trial.

BACKGROUND: Exogenous surfactant preparations vary in their constitution and biophysical properties. Synthetic and animal-derived preparations lower the rate of death compared with controls. No significant differences in mortality or important long-term clinical outcomes have been shown between them in randomised trials. We did a randomised controlled trial to compare pumactant, a synthetic surfactant, with poractant alfa, an animal-derived surfactant, both of which are widely used in the UK. METHODS: We enrolled 212 neonates born between 25 weeks' and 29 weeks and 6 days' gestation who were intubated for presumed surfactant deficiency and were free from life-threatening malformations. We randomly assigned 105 neonates poractant alfa, and 107 pumactant. The primary outcome was duration of high-dependency care and mortality was a secondary outcome. Analysis was by intention to treat. FINDINGS: Outcome data were analysed for 199 babies. The trial was stopped on the recommendation of the data and safety monitoring committee because mortality assumed a greater importance than the primary outcome. Predischarge mortality differed significantly between groups, in favour of poractant alfa (14.1 vs 31.0%, p=0.006; odds ratio 0.37 [95% CI 0.18-0.76). This difference was sustained after adjustment for centre, gestation, birthweight, sex, plurality, and use of antenatal steroids. INTERPRETATION: Mortality was unexpectedly lower among neonates who received poractant alfa than among those who received pumactant, and was independent of all the variables we investigated. Stopping the trial early may have widened the difference between the treatment groups.

A new in vivo microvascular preparation of the hamster ovary.

Ovarian function in the cycling female is intimately related to and dependent upon significant microvascular regulation and restructuring. To enable investigation of the microvascular determinants of ovarian function, we present an in vivo preparation of the golden hamster ovary. The preparation does not compromise the ovarian vascular supply. The viability and responsiveness of the preparation were confirmed by quantifying arteriolar responses to vasoactive agents in 17 hamsters. Small surface arterioles (mean diameter 15-16 microns) responded with statistically significant changes in diameter to adenosine and oxygen and showed significant, dose-dependent constriction in response to norepinephrine and the NO synthase inhibitor L-NAME. Other key findings included extremely high microvascular permeability that varied with the day of the estrous cycle and functionally significant architectural features of the utero-ovarian vascular network. Potential applications of the preparation include elucidation of the role of the microvasculature in follicular development and luteal regression, investigation of utero-ovarian crossregulation, and development of a model for the study of ovarian angiogenesis and vascular regression.