Antenatal antecedents of a small head circumference at age 24-months post-term equivalent in a sample of infants born before the 28th post-menstrual week

Background

Little is known about the antecedents of microcephaly in early childhood among children born at extremely low gestational age.

Aim

To identify some of the antecedents of microcephaly at age two years among children born before the 28th week of gestation.

Study design

Observational cohort study.

Subjects

1004 infants born before the 28th week of gestation.

Outcome measures

Head circumference Z-scores of <−2 and ≥−2, <−1.

Results

Risk of microcephaly and a less severely restricted head circumference decreased monotonically with increasing gestational age. After adjusting for gestational age and other potential confounders, the risk of microcephaly at age 2 years was increased if microcephaly was present at birth [odds ratio: 8.8 ((95% confidence interval: 3.7, 21)], alpha hemolytic Streptococci were recovered from the placenta parenchyma [2.9 (1.2, 6.9)], the child was a boy [2.8 (1.6, 4.9)], and the child's mother was not married [2.5 (1.5, 4.3)]. Antecedents associated not with microcephaly, but with a less extreme reduction in head circumference were recovery of Propionibacterium sp from the placenta parenchyma [2.9 (1.5, 5.5)], tobacco exposure [2.0 (1.4, 3.0)], and increased syncytial knots in the placenta [2.0 (1.2, 3.2)].

Conclusions

Although microcephaly at birth predicts a small head circumference at 2 years among children born much before term, pregnancy and maternal characteristics provide supplemental information about the risk of a small head circumference years later. Two findings appear to be novel. Tobacco exposure during pregnancy, and organisms recovered from the placenta predict reduced head circumference at age two years.     

Neonatal outcome in hypertensive disorders of pregnancy

Background

Hypertensive disorders in pregnancy account for increased perinatal morbidity and mortality when compared to uneventful gestations.

Aims

To analyze perinatal outcome of pregnancies complicated by different kinds of hypertension to uncomplicated pregnancies in a series of Italian women and to compare our data with series from other countries.

Study design

The sample was divided into four groups of hypertensive women: chronic hypertension (CH), gestational hypertension (GH), preeclampsia (PE), and chronic hypertension complicated by preeclampsia (CHPE). One thousand normal pregnancies served as controls.

Subjects

Neonatal features of the offspring of 965 Italian women with hypertension in pregnancy were evaluated.

Measures

Gestational age, birthweight and the rate of small for gestational age were the outcomes. Perinatal asphyxia and mortality were also assessed.

Results

Gestational age, the mean of birth weight and birth percentile were significantly lower in all groups with hypertensive complications when compared with controls. The rate of very early preterm delivery (< 32 weeks) was 7.8% in CH, 5.9% in GH, 21.2% in PE and 37.2% in CHPE while it was to 1.2% in the control group. The rate of SGA was globally 16.2% in CH, 22.8% in GH, 50.7% in PE, 37.2% in CHPE and 5% in controls. The rate of SGA in PE was much higher than reported in series from other countries.

Conclusion

Comparing our data with those reported from other countries, it is evident that the rate of fetal growth restriction in PE we found in our center, is significantly higher even in the presence of a global lower incidence of PE.     

The ELGAN study of the brain and related disorders in extremely low gestational age newborns

Background

Extremely low gestational age newborns (ELGANs) are at increased risk for structural and functional brain abnormalities.

Aim

To identify factors that contribute to brain damage in ELGANs.

Study design

Multi-center cohort study.

Subjects

We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites; 1201 (80%) survived to 2 years corrected age. Information about exposures and characteristics was collected by maternal interview, from chart review, microbiologic and histological examination of placentas, and measurement of proteins in umbilical cord and early postnatal blood spots.

Outcome measures

Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions, on protocol cranial ultrasound scans; head circumference and developmental outcomes at 24 months adjusted age, i.e., cerebral palsy, mental and motor scales of the Bayley Scales of Infant Development, and a screen for autism spectrum disorders.

Results

ELGAN Study publications thus far provide evidence that the following are associated with ultrasongraphically detected white matter damage, cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor premature rupture of membranes, or cervical insufficiency; recovery of microorganisms in the placenta parenchyma, including species categorized as human skin microflora; histological evidence of placental inflammation; lower gestational age at delivery; greater neonatal illness severity; severe chronic lung disease; neonatal bacteremia; and necrotizing enterocolitis.

Conclusions

In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our study is the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma.     

What (not) to do before delivery? Prevention of fetal meconium release and its consequences

Background

Meconium-stained amniotic fluid is a common occurrence which places the mother at risk of escalating obstetric interventions, and the baby at risk of meconium aspiration syndrome.

Methods

The Cochrane Library was searched for interventions related to care before delivery with useful evidence on the outcomes ‘meconium-stained amniotic fluid’ and ‘meconium aspiration syndrome’.

Findings

Curtailment of post-term pregnancy reduces the occurrence of meconium-stained amniotic fluid, and meconium aspiration syndrome.Uterine stimulants, particularly misoprostol, are associated with occurrence of meconium-stained amniotic fluid.Amniotomy during labour may be a risk factor for meconium aspiration syndrome.There is little research evidence on the benefits or otherwise of obstetric interventions such as expedited delivery for meconium-stained liquor without other evidence of fetal distress. Amnioinfusion for meconium-stained amniotic fluid improves neonatal outcome only in settings with limited peripartum surveillance. There is insufficient evidence to support the use of amnioinfusion for meconium-stained liquor in settings with adequate peripartum surveillance.     

Predictability of cerebral palsy in a high-risk NICU population

Aim

This study aims to create a predictive model for the assessment of the individual risk of developing cerebral palsy in a large cohort of selected high-risk infants.

Patients and methods

1099 NICU-admitted high-risk infants were assessed up to the corrected age of at least 12 months. CP was categorized relative to subtype, distribution and severity. Several perinatal characteristics (gender, gestational age, multiple gestation, small for gestational age, perinatal asphyxia and duration of mechanical ventilation), besides neonatal cerebral ultrasound data were used in the logistic regression model for the risk of CP.

Results

Perinatal asphyxia, mechanical ventilation > 7 days, white matter disease except for transient echodensities < 7 days, intraventricular haemorrhage grades III and IV, cerebral infarction and deep grey matter lesions were recognized as independent predictors for the development of CP. 95% of all children with CP were correctly identified at or above the cut-off value of 4.5% probability of CP development. Higher gestational age, perinatal asphyxia and deep grey matter lesion are independent predictors for non-spastic versus spastic CP (OR = 1.1, 3.6, and 7.5, respectively). Independent risk factors for prediction of unilateral versus bilateral spastic CP are higher gestational age, cerebral infarction and parenchymal haemorrhagic infarction (OR = 1.2, 31, and 17.6, respectively). Perinatal asphyxia is the only significant variable retained for the prediction of severe CP versus mild or moderate CP.

Conclusion

The presented model based on perinatal characteristics and neonatal US-detected brain injuries is a useful tool in identifying specific infants at risk for developing CP.     

A model to predict motor performance in preterm infants at 5 years

Background

Approximately 60% of preterm infants who are assessed at 5 years for motor performance in a standardized multidisciplinary follow-up program are found to have normal results, indicating that, for these children, routine motor assessment at this age is unnecessary.

Aim

To improve the efficiency of our follow-up practice for motor assessment by developing a model to predict motor performance of preterm infants at 5 years with a maximal sensitivity (≥90%).

Study design

Longitudinal design.

Subjects

We included preterm infants (n = 371) with a gestational age of ≤32 weeks; children with severe disabilities were excluded.

Outcome measures

The Movement Assessment Battery for Children (M-ABC) at 5 years with ‘delayed’ motor performance (<15 percentile) was the dependent variable. As factors in the model, we used twenty neonatal risk factors, the maternal education level, the Motor Scale and the Behavior Rating Scale (BRS) of the Bayley Scales of Infant Development, 2nd edition, at 2½ years.

Results

Binary logistic regression analysis revealed that the prediction model (n = 345) reached a sensitivity of 94%. Five factors contributed significantly (p < 0.05) to the model: a Motor Scale PDI <90 and a BRS ‘motor quality’ <26 percentile, and the neonatal risk factors gestational age <30 weeks, male gender and intra-ventricular hemorrhage.

Conclusion

The prediction model can improve the efficiency of follow-up practice for motor assessment by 37% at 5 years. Applying this model, we would not have assessed 129 children and would have missed six children.     

The relation between umbilical cord characteristics and the outcome of external cephalic version

Background

Umbilical cords of fetuses in breech presentation differ in length and coiling from their cephalic counterparts and it might be hypothesised that these cord characteristics may in turn affect ECV outcome.

Aim

To investigate the relation between umbilical cord characteristics and the outcome of external cephalic version (ECV).

Study design

Prospective cohort study.

Subjects

Women (> 35 weeks gestation) with a singleton fetus in breech presentation, suitable for external cephalic version. Demographic, lifestyle and obstetrical parameters were assessed at intake. ECV success was based on cephalic presentation on ultrasound post-ECV. Umbilical cord length (UCL) and umbilical coiling index (UCI) were measured after birth.

Outcome measure

The relation between umbilical cord characteristics (cord length and coiling) and the success of external cephalic version.

Results

ECV success rate was overall 79/146 (54%), for multiparas 37/46(80%) and for nulliparas 42/100 (42%). Multiple logistic regression showed that UCL (OR: 1.04, CI: 1.01-1.07), nulliparity (OR: 0.20, CI: 0.08-0.51), frank breech (OR: 0.37, 95% CI: 0.15-0.90), body mass index (OR: 0.85, CI: 0.76-0.95), placenta anterior (OR: 0.27, CI: 0.12-0.63) and birth weight (OR: 1.002, CI: 1.001-1.003) were all independently related to ECV success.

Conclusions

Umbilical cord length is independently related to the outcome of ECV, whereas umbilical coiling index is not.     

The role of intestinal bifidobacteria on immune system development in young rats

Aim

The effects of intestinal bifidobacteria on the development of immunity in early life were explored.

Methods

Neonatal SD rats born and housed under strict barrier systems were fed from birth with sufficient antibiotics (bifidobacteria minimisation group) or supplemented daily with 1 × 10¹⁰ colony-forming units of live Bifidobacterium longum (bifidobacteria supplementation group). Relevant indices of immune development were determined at one, three and six weeks old.

Results

Compared to the control group, minimisation of the intestinal bifidobacteria delayed maturation of dendritic cells in Peyer's Patches and the development of T cells in the thymus, increased IL-4 secretion in the plasma, down-regulated IL-12, IL-10 mRNA and the interferon-γ/IL-4 mRNA ratio in intestinal mucosa, decreased interferon-γ mRNA in cultured peripheral blood mononuclear cells (PBMCs), and reduced immunoglobulin-M production in cultured PBMCs. Conversely, supplementation with bifidobacteria promoted dendritic cell maturation in Peyer's Patches, up-regulated IL-12, IL-10, interferon-γ mRNA and the interferon-γ/IL-4 ratio in intestinal mucosa, increased interferon-γ gene expression in cultured PBMCs, and raised immunoglobulin-M secretion in cultured PBMCs.

Conclusions

Intestinal bifidobacteria could promote the maturation of dendritic cells and its expression of IL-12 locally in the gut, influence the development of T cells in the thymus, favour the development of T-helper cell type 1 response by increasing the local and systemic expression of interferon-γ and ensure the intestinal regulatory T cell response by promoting the local expression of IL-10. In addition, they enhance antibody synthesis by PBMCs, thereby affecting the development of both the gut and systemic immunity in early life.     

Expression of aquaporins early in human pregnancy

Background

Aquaporins (AQPs) constitute a family of channel proteins implicated in transmembrane water transport. Thirteen different AQPs (AQP0–12) have been described but their precise biologic function still remains unclear. AQPs 1, 3, 4, 8, and 9 expression has been described in human chorion, amnion and placenta; however, AQP4 is the only that has been identified in the first trimester of human pregnancy.

Objective

To assess multiplicity of AQPs expression from 10th to 14th week gestation.

Population and methods

Chorionic villi samples (CVS) collected in pregnant women for prenatal diagnosis were analysed by real time-PCR to assess cDNA expression of AQPs 1, 2, 3, 4, 5, 6, 7, 8, 9, and 11, and compared with AQPs expression in placentas from normal term pregnancies.

Results

26 CVS corresponding to 26 pregnant women (age: 32.7 ± 4.5 years; gestational age: 12.4 ± 0.9 weeks) and 10 placental samples corresponding to normal term pregnancies were analysed. In CVS karyotype was normal in 16 cases, trisomy in 6 cases, mosaicism in 1 and unknown in 1. We found high mRNA expression for AQPs 1, 3, 9 and 11, low for AQPs 4, 5, and 8, and non-detectable for AQPs 2, 6, and 7 in chorionic villi.

Conclusions

This is the first study systematically assessing the expression of a multiplicity of AQPs in chorionic villi samples between 10th and 14th weeks of gestation. High expression of AQP11 has been identified for the first time in early stages of human pregnancy. Chromosomal abnormalities did not alter AQPs' expression.     

Stability of neurocranial signs in the first two years of life in infants at risk

Background

Acknowledgement of low-severity/high-prevalence disabilities in infants born preterm singles out the need to identify early markers of brain impairments which could predict these late emergent disabilities. The neurological status as assessed by the Amiel-Tison Neurological Assessments (ATNA) has been proposed as one such potential marker. However, the stability of the ATNA has never been formally assessed.

Aim

This study aimed to assess the stability of the ATNA.

Study design

A total of 89 infants born preterm with a gestational age ranging from 29 0/7 to 37 0/7 weeks inclusively and a birth weight below 2500 g were followed during their first two years of life (term age, 4, 8, 12 and 24 months corrected age) in a clinical context.

Results

Of these, 62 children (69.7%) were classified in the same category on the five assessments while 14 (15.7%) had only one divergent result and 13 (14.6%) had two divergent results over the follow-up. The neurological status throughout the assessments remains stable according to Cochran's Q.

Conclusion

As the neurological status identified by the ATNA remained stable throughout repeated measurements in a regular clinical context and has been shown to correlate with later developmental performances, it should be included as a criterion to target children at risk and used during follow-up.     

HHV-8-associated Kaposi sarcoma in a child with IFNgammaR1 deficiency

Objectives

Mediterranean classic Kaposi sarcoma (KS) of childhood is rare and unexplained. Our objective is to describe the case of a child with complete IFNγR1 deficiency and severe mycobacterial disease in whom Kaposi sarcoma (KS) developed.

Results

Disseminated mycobacterial infection began at the age of 5 months, and at 11 years of age the child had disseminated KS lesions. The histologic appearance of these lesions was typical, with endothelial and spindle cell proliferation. Human herpesvirus-8 (HHV-8)-associated antigens were detected in situ by immunohistochemistry. HHV-8 DNA of K1 molecular subtype A was amplified from tissue lesions, and HHV-8-specific antibodies were detected in the patient's serum. The child died at 12 years of age of disseminated mycobacterial disease and KS.

Conclusions

This is the first identification of a well-defined primary immunodeficiency in a child with KS. Inherited disorders of IFN-γ-mediated immunity and severe mycobacterial disease may predispose HHV-8-infected children to KS.     

Estimating the relative contributions of maternal genetic, paternal genetic and intrauterine factors to offspring birth weight and head circumference

Background

Genetic factors and the prenatal environment contribute to birth weight. However, very few types of study design can disentangle their relative contribution.

Aims

To examine maternal genetic and intrauterine contributions to offspring birth weight and head circumference. To compare the contribution of maternal and paternal genetic effects.

Study design

Mothers and fathers were either genetically related or unrelated to their offspring who had been conceived by in vitro fertilization.

Subjects

423 singleton full term offspring, of whom 262 were conceived via homologous IVF (both parents related), 66 via sperm donation (mother only related) and 95 via egg donation (father only related).

Measures

Maternal weight at antenatal booking, current weight and maternal height. Paternal current weight and height were all predictors. Infant birth weight and head circumference were outcomes.

Results

Genetic relatedness was the main contributing factor between measures of parental weight and offspring birth weight as correlations were only significant when the parent was related to the child. However, there was a contribution of the intrauterine environment to the association between maternal height and both infant birth weight and infant head circumference as these were significant even when mothers were unrelated to their child.

Conclusions

Both maternal and paternal genes made contributions to infant birth weight. Maternal height appeared to index a contribution of the intrauterine environment to infant growth and gestational age. Results suggested a possible biological interaction between the intrauterine environment and maternal inherited characteristics which suppresses the influence of paternal genes.     

Behavioural problems at the age of eleven years in preterm-born children with or without fetal brain sparing: A prospective cohort study

Background

In severe intrauterine growth restriction (IUGR) due to placental insufficiency a haemodynamic adaptation occurs, resulting in preferential blood flow to the fetal brain (brain sparing). With Doppler ultrasound an increased ratio between the umbilical and the cerebral artery pulsatility index (U/C ratio) can be demonstrated. IUGR is associated with impaired neurodevelopmental outcome.

Objective

Evaluation of the effect of fetal brain sparing on behavioural problems at eleven years in premature born children.

Methods

Prospective cohort study in premature children born in 1989, with a gestational age of 26 0/7 to 33 0/7 weeks. An U/C ratio > 0.72 was defined as brain sparing. Behavioural problems were assessed with the parent-reported Child Behaviour Check List (CBCL) and the Teacher's Report Form (TRF). T scores > 60 for total problem score and subscales of internalizing and externalizing behaviour, were considered abnormal.

Results

Ninety-eight of the 116 survivors were assessed, of which 31 with antenatally established fetal brain sparing. According to the CBCL-total problem score 23.3% of the premature born babies in the brain sparing group had behavioural problems compared with 22.8% of those without brain sparing. According to the TRF-total problem score the percentages were 21.4% and 20.0%, respectively. Logistic regression analysis failed to show a significant association of U/C ratio with behavioural problems. In this model oxygen dependency at 28 days, IQ < 85 at five years, cranial ultrasound abnormalities, fetal growth ratio < 0.80, Apgar scores < 7 after 5 min and birth weight < p10 contributed significantly.

Conclusion

In this cohort brain sparing itself has no significant association with behavioural problems at eleven years.     

Infertility, infertility treatment, and mixed-handedness in children

Background

Mixed-handedness, which may reflect atypical brain laterality, has been linked to a number of medical conditions as well as prenatal stress.

Aims

The aim of the study was to examine whether infertility or infertility treatment was associated with an increased risk of mixed-handedness in children.

Study design, subjects and outcome measures

We used data from three population-based birth cohorts in Denmark: the Aalborg-Odense Birth Cohort (1984-1987), the Aarhus Birth Cohort (1990-1992) and the Danish National Birth Cohort (1996-2002) (N = 7728, 5720 and 29486, respectively). Data on time to pregnancy and infertility treatment were collected during pregnancy. Handedness was reported in a follow-up questionnaire when the children were at least 7 years old. Children were categorized as mixed-handed if their mothers reported that they used both hands equally.

Results

Children born after infertility treatment, particularly intrauterine insemination, had a higher risk of being mixed-handed compared to children of fertile couples with a time to pregnancy ≤ 12 months (odds ratio 1.41, 95% confidence interval 1.09-1.82). Children of couples with unplanned pregnancies, particularly after an oral contraceptives failure, were also more likely to be mixed-handed. There was no association between a long waiting time to pregnancy and mixed-handedness in children.

Conclusions

Children born after infertility treatment, particularly intrauterine insemination, and children exposed to oral contraceptives during early gestation may have a higher risk of being mixed-handed.     

General movements in the perinatal period and its relation to echogenicity changes in the brain

Background

In preterm born infants abnormal general movements (GMs) generally normalize before three months post term, but may persist when perinatal brain injury is present.

Aims

To assess the continuity of GM quality from fetal to early neonatal period and its relation to brain echogenicity changes.

Study design

Prospective study examining GMs and three vulnerable brain areas before and 7 days after birth. The quality of GMs was classified as normal or abnormal by Gestalt-perception. The brain was examined for moderate echogenicity changes (periventricular: brighter than choroid plexus, intraventricular: filling equal or more than 50% of the ventricle, and locally increased basal ganglia/thalami).

Subjects

94 fetuses from pregnancies complicated by preterm hypertensive disorders or labour at a gestational age between 26 and 34 weeks.

Outcomes measures

Correlations of fetal GMs, echogenicity changes, and clinical parameters (e.g. gestational age, parity, hypertensive disorders or preterm labour, oligohydramnios and fetal growth restriction) with neonatal GMs.

Results

Fetal GMs were abnormal in 64%, normalizing in 68% within 7 days after birth. Fetal GMs were significantly related to postnatal GMs (p = 0.045). Moderate fetal brain echogenicity changes and clinical parameters were not significantly related to neonatal GM.

Conclusions

In this population of pregnancies compromised by hypertensive disorders or preterm labour fetal GMs correlated with neonatal GMs. Presence of moderate echogenicity changes in the fetal brain was not related to neonatal GMs.     

Preconception risk factors and SGA babies: Papilloma virus, omega 3 and fat soluble vitamin deficiencies

Background

Small for gestational date (SGA) babies have a poor ‘whole of life’ prognosis and major factors affecting SGA may be present prior to conception.

Aims

To discover whether lifestyle risk factors can be identified in women planning a pregnancy.

Study design

Prospective study of women who were planning a pregnancy, who agreed to answer a detailed 250 question questionnaire prior to commencing to try to conceive, to being monitored, and within 7 days of a positive pregnancy test having a vaginal ultrasound scan and answering further questions about the events since the last menstrual period. Details of all outcomes were recorded.

Subjects

585 couples completed the study.

Outcome measures

The relationships between birth weights and questionnaire data was analysed using SPSS and parametric statistical analysis.

Results and conclusions

401 women (67.9% of all participants) had live births. Eleven babies (2.7%) were less than the 3rd percentile in weight and a further 22 babies (5.4%) were between the 3rd and 10th weight percentiles. Mothers of SGA babies had a lower than average education, diets that were low in meat, fish, dairy foods and nuts or seeds and were more likely to conceive in the winter. Mothers of SGA babies were significantly more likely to have had a recent abnormal Pap smear test. Air travel in the month of conception was a risk factor in having a baby less than 10th percentile.

Conclusion

The quality of lifestyle prior to conception is critical: prenatal counselling needs to be undertaken prior to conception.     

Care Coordination in the Spina Bifida Clinic Setting: Current Practice and Future Directions

Introduction

Although the potential benefits of care coordination are widely recognized, little is known about care coordination in the multidisciplinary spina bifida clinic setting. This study examined several aspects of care coordination in this environment.

Method

We conducted semi-structured interviews with clinic staff (N = 43) and focus groups with caregivers (N = 38) at seven spina bifida clinics in the United States.

Results

Clinic staff described several primary goals of care coordination, including coordinating multiple services during one visit to ease the burden on families. Although the structure of care coordination varied across the clinics, several clinics had a dedicated care coordinator. Barriers and facilitators to care coordination included staffing issues, clinic day logistics, community resources, and family-related concerns. Despite challenges associated with care coordination processes, clinic staff and caregivers alike believed that care coordination is beneficial.

Discussion

Study findings suggest ways that care might be coordinated optimally in spina bifida clinics. A synthesis of these findings for clinics interested in implementing care coordination or improving the care coordination services they currently offer is provided.     

Benign convulsions in newborns and infants: Occurrence, clinical course and prognosis

Background

During early development severe epilepsies may appear, some with well established occurrence. Benign non-epileptic and epileptic paroxysmal syndromes with excellent prognosis occur in the same period. There are no exact data on their occurrence.

Aim

We have reviewed medical histories of children with benign non-epileptic or benign epileptic events: benign myoclonus of early infancy, benign neonatal sleep myoclonus, benign sleep myoclonus in infancy, benign partial epilepsy in infancy (BPEI) and benign infantile familial convulsions (BIFC) were established. The occurrence, clinical characteristics and prognosis of these syndromes were evaluated.

Methods

Inclusion criteria were met in 31 children. Research included retrospective analysis of clinical characteristics, laboratory values, neuroimaging and neurophysiological assessments, followed by evaluation of psychosocial development with the use of the Strengths and Difficulties Questionnaire (SDQ), fulfilled by parents.

Results

In our group the incidence of benign non-epileptic convulsions was 6.69 per 10 000 live births and the incidence of benign epileptic convulsions was 1.35 per 10 000. Male/female ratio in the group of children with non-epileptic events was 2.1:1. Among non-epileptic group 5 out of 23 children and among epileptic group 3 out of 8 children had minimal, mild or moderate abnormalities at neurological assessment at the time of the first clinical examination. Nonspecific changes in laboratory values were seen in 6 out of 23 in the non-epileptic and in 1 out of 8 children in the epileptic group. Neurophysiological assessments showed subtle changes in 4/23 in the non-epileptic and 6/8 in the epileptic group. Neuroimaging was not optimal in 5/23 with non-epileptic and 3/8 with epileptic events. Analysis of SDQ did not show significant deviations in psyhosocial development. Statistically significant deviation was observed only in relations with peers (p = 0.009).

Conclusions

Benign neonatal and infantile convulsions are more frequent than severe epilepsies of the same age period. Results show higher proportion of males with benign non-epileptic conditions. No deviations in further development was found. Laboratory values, neuroimaging and neurophysiological assessments were normal or nonspecifically changed.     

Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: a prospective, observational, multicenter study

Background

Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia.

Aims

To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia.

Study design

prospective, observational, multicenter.

Subjects

2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy.

Methods

All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin > 17 mg/dL or need for phototherapy.

Results

Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age. Conclusions: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48 h of life ahead.     

Gender-related effects of prenatal administration of estrogen and progesterone receptor antagonists on VEGF and surfactant-proteins and on alveolarisation in the developing piglet lung

Background

Vascular endothelial growth factor (VEGF) is essential for embryonic lung development and has been shown to be regulated by estradiol (E2) and progesterone (P).

Aim

To investigate the effects of prenatal E2 and P withdrawal by specific receptor antagonists on the mRNA expression of VEGF, surfactant proteins (SP-B and SP-C) and on alveolarisation in lung tissue of male and female pig fetuses.

Methods

Fetuses from 10 sows were randomized to receive either both an intramuscular injection of the E2 receptor blocker ICI 182.780 and the P receptor blocker RTI 3021-022 (ICI + RTI, n = 5) or a placebo injection (n = 5) at 90 days of gestation (DOG, 115 = term). After delivery by cesarean section on 114 DOG, tissue of the left lingula of the piglet's lung (28 placebo, 26 ICI + RTI) was obtained to determine the mRNA expression of VEGF, SP-B and SP-C. Lungs from 15 placebo and 14 ICI + RTI group piglets were removed and alveolar counts performed.

Results

The ICI + RTI group showed significantly lower SP-C mRNA expression and alveolar counts compared to the placebo group (p = 0.04 and 0.03, respectively). Diminished alveolarisation in the ICI + RTI group was mainly due to the reduction of alveolar counts in male piglets (p = 0.02). Within the placebo group VEGF and SP-B mRNA expression in male piglets were significantly lower compared to female piglets (p = 0.01 and 0.004, respectively). ICI + RTI treatment abolished this gender-related difference.

Conclusion

Estradiol and P antagonism affected gender-related differences of key proteins for pulmonary function and development and especially in males was associated with diminished alveolarisation.