Placental pathology is associated with illness severity in preterm infants in the first twenty-four hours after birth

Background

Placental pathology is associated with long-term neurological morbidity. Little is known about the association of placental pathology and illness severity directly after birth in preterm infants.

Objective

To determine the association between placental pathology and illness severity in preterm infants during the first 24 h after birth.

Study design

Placentas of 40 preterm infants, born after singleton pregnancies (gestational age 25.4-31.7 weeks, birth weight 560-2250 g) were assessed for histopathology. Illness severity was measured using the Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE). A high SNAPPE reflects high illness severity.

Results

Examination of the 40 placentas revealed: pathology consistent with maternal vascular underperfusion (MVU) (n = 24), ascending intrauterine infection (AIUI) (n = 17), villitis of unknown aetiology (VUE) (n = 6), foetal thrombotic vasculopathy (FTV) (n = 6), elevated nucleated red blood cells (NRBCs) (n = 6), and chronic deciduitis (n = 10). SNAPPE ranged from 1 to 53 (median 10). Infants with elevated NRBCs had a higher SNAPPE than infants without elevated NRBCs (median 30 vs. 10, p = 0.014). The same was found for the presence of FTV (median 30 vs. 10, p = 0.019). No relation existed between SNAPPE and the other placental pathologies.

Conclusions

Elevated NRBCs and FTV were associated with higher illness severity during the first 24 h after birth in preterm infants. Ascending intrauterine infection was not associated with high illness severity.     

Infant head circumference growth is saltatory and coupled to length growth

Background

Rapid growth rates of head circumference and body size during infancy have been reported to predict developmental pathologies that emerge during childhood.

Aims

This study investigated whether growth in head circumference was concordant with growth in body length.

Subjects

Forty infants (16 males) were followed between the ages of 2 days and 21 months for durations ranging from 4 to 21 months (2616 measurements).

Study design

Longitudinal anthropometric measurements were assessed weekly (n = 12), semi-weekly (n = 24) and daily (n = 4) during home visits. Individual head circumference growth was investigated for the presence of saltatory patterns. Coincident analysis tested the null hypothesis that head growth was randomly coupled to length growth.

Results

Head circumference growth during infancy is saltatory (p < 0.05), characterized by median increments of 0.20 cm (95% confidence interval, 0.10-0.30 cm) in 24-h, separated by intervals of no growth ranging from 1 to 21 days. Daily assessments identified that head growth saltations were coupled to length growth saltations within a median time frame of 2 days (interquartile 0-4, range 1-8 days). Assessed at semi-weekly and weekly intervals, an average 82% (SD 0.13) of head growth saltations was non-randomly concordant with length growth (p ≤ 0.006).

Conclusions

Normal infant head circumference grows by intermittent, episodic saltations that are temporally coupled to growth in total body length by a process of integrated physiology that remains to be described.     

Circulating adipocyte fatty acid binding protein levels in healthy preterm infants: Positive correlation with weight gain and total-cholesterol levels

Background

Adipocyte fatty acid binding protein (a-FABP) has been suggested to play an important role in the pathogenesis of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance, and, possibly, other components of metabolic syndrome.

Aim

To determine circulating levels of a-FABP in preterm infants and examine possible associations of a-FABP with metabolic indices (serum lipids, glucose, and insulin levels, and homeostasis model assessment index of insulin resistance [HOMA-IR]), levels of leptin and adiponectin, anthropometric parameters and weight gain.

Study design

Prospective cohort study.

Subjects

55 healthy preterm (mean [SD] gestational age 32.8 [1.8] weeks) and 23 fullterm infants (reference group).

Outcome measures

Serum a-FABP, lipids, glucose, insulin, leptin and adiponectin levels at 31.9 [10.4] days of life.

Results

Serum a-FABP levels did not differ significantly between preterm and fullterm infants. A-FABP levels correlated positively with total-cholesterol [total-C] in both preterm and fullterm infants (β = 0.33; p = 0.01 and β = 0.33; p = 0.04, respectively). In addition to total-C, weight gain correlated independently with a-FABP levels in preterm infants (β = 0.36, p = 0.01).

Conclusions

An association between a-FABP levels and indices of insulin resistance was not present in infants studied. As the development of insulin resistance in children born prematurely is possibly associated with weight gain in early postnatal life, follow-up of our study population is necessary to demonstrate whether a-FABP levels, shown to correlate with weight gain in preterm infants, are a predictive marker for the later development of insulin resistance in these infants.     

Amplitude integrated electroencephalographic activity in infants with congenital heart disease before surgery

Background

Infants with congenital heart disease (CHD) are at risk for brain injury. An accurate tool to monitor brain function is amplitude integrated EEG (aEEG). It records both background patterns and electrographic seizure activity (EA).

Aims

Our aim was to determine aEEG patterns in infants with CHD and to determine the differences between infants with a cyanotic or an acyanotic CHD.

Study design and subjects

Sixty-two full term newborns had either a cyanotic CHD (transposition of the great arteries (n = 24)) or an acyanotic CHD (hypoplastic left heart syndrome (n = 26), critical aortic valve stenosis (n = 1) or aortic coarctation (n = 11)). The background patterns, sleep-wake cycling (SWC), and EA were assessed. The first 72 h after starting prostaglandin E₁-therapy were used for analysis.

Results

The background patterns were mildly abnormal in 45% of the infants and severely abnormal at some point during the recording in 14% of the infants. We found no differences in background patterns between the two groups. EA was present in 12 (19%) infants. EA was more frequent in infants with acyanotic CHD (OR 9.4, 95% CI 1.1-78, p = 0.039). SWC was equally frequent in infants with cyanotic and infants with acyanotic CHD. A severely abnormal aEEG and EA were associated with more profound acidosis.

Conclusions

Before surgery the majority of infants with a CHD had an abnormal aEEG. aEEG helped to identify EA and it was a useful tool to evaluate brain function prior to surgery in CHD.     

Quantitative analysis of maturational changes in EEG background activity in very preterm infants with a normal neurodevelopment at 1 year of age

Background

The electroencephalographic (EEG) background pattern of preterm infants changes with postmenstrual age (PMA) from discontinuous activity to continuous activity. However, changes in discontinuity have been investigated by visual analysis only.

Aim

To investigate the maturational changes in EEG discontinuity in healthy preterm infants using an automated EEG detection algorithm.

Study design

Weekly 4 h EEG recordings were performed in preterm infants with a gestational age (GA) < 32 weeks and normal neurological follow-up at 1 year. The channel C3-C4 was analyzed using an algorithm which automatically detects periods of EEG inactivity (interburst intervals). The interburst-burst ratio (IBR, percentage of EEG inactivity during a moving time window of 600 s) and mean length of the interburst intervals were calculated. Using the IBR, discontinuous background activity (periods with high IBR) and continuous background activity (periods with low IBR) were automatically detected and their mean length during each recording was calculated. Data were analyzed with regression and multivariate analysis.

Results

79 recordings were performed in 18 infants. All recordings showed a cyclical pattern in EEG discontinuity. With advancing PMA, IBR (R² = 0.64; p < 0.001), interburst interval length (R² = 0.43; p < 0.001) and length of discontinuous activity (R² = 0.38; p < 0.001) decreased, while continuous activity increased (R² = 0.50; p < 0.001). Multivariate analysis showed that all EEG discontinuity parameters were equally influenced by GA and postnatal age.

Conclusion

Analyzing EEG background activity in preterm infants is feasible with an automated algorithm and shows maturational changes of several EEG derived parameters. The cyclical pattern in IBR suggests brain organisation in preterm infant.     

Effect of gender and hand laterality on pain processing in human neonates

Background

Previous studies in adults have reported that handedness and gender can affect pain perception. However, it is currently unclear when these differences emerge in human development. Therefore, we examined prefrontal responses to pain stimulation among newborns during their first acute pain experience after birth.

Methods

Forty newborns at 4-6 days postnatal age were observed during clinically required blood sampling while prefrontal activation was measured with near infrared spectroscopy. Blood sampling in this study was the first experience of a procedure involving skin breaking for these infants. We divided subjects into a right-hand stimulation group (n = 21) and a left-hand stimulation group (n = 19), depending on whether blood was sampled from the right or the left hand. A three-way analysis of variance (ANOVA) was conducted to examine the effects of several variables on the magnitude of the oxy-Hb value in response to pain stimulus, including stimulus side (right hand or left hand), gender (male or female), recording side (right prefrontal area or left prefrontal area) and interactions between these variables.

Results

The data revealed a significant effect of stimulus side (F (1, 72) = 9.892, P = 0.002), showing that the right-hand stimulation induced a greater prefrontal activation than the left-hand stimulation. No significant gender difference or interactions were found.

Conclusion

Our findings suggest that hand laterality affects pain perception even in neonates. However, gender differences in pain perception did not appear to occur during the neonatal period. Further investigations using brain-imaging techniques are required to identify laterality- or gender-related differences in pain processing in humans.     

Leptin determination in colostrum and early human milk from mothers of preterm and term infants

Background

Leptin is involved in the regulation of food intake and energy expenditure and is therefore important for growth and brain development. Analytical methods used for leptin measurement in human milk differ widely in the literature and yield varying results.

Aims

To compare different preparation methods for the analysis of leptin in human milk and to investigate the leptin levels in colostrum and mature human milk from mothers of preterm or term infants.

Methods

Mothers delivering a preterm (n = 37) or a term infant (n = 40) were recruited for a prospective study and were ask to collect breast milk on the 3rd and 28th day of lactation. Leptin, protein and fat concentrations were analysed. Clinical data of mother and child were recorded prospectively.

Results

Skim milk was most appropriate for leptin analysis. Human milk leptin concentrations did not differ between preterm and term human milk. In term milk, leptin concentration on day 28 was lower than on day 3 (p < 0.05). Milk leptin levels on the 3rd and 28th day were positively correlated with mothers' body mass index, but not with fat content in milk.

Conclusion

Skim milk was the most stabile preparation for leptin analysis. Preterm and term human milk contain leptin in equal concentrations. Human milk leptin depends on mothers' body mass index.     

Early identification of the risk for free radical-related diseases in preterm newborns

Background

Despite recent advances in preterm newborns healthcare, perinatal pathologies and disabilities are increasing. Oxidative stress (OS) is determinant for the onset of an unbalance between free radicals (FRs) production and antioxidant systems which plays a key role in pathogenesis of pathologies such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), grouped as ‘free radical-related diseases’ (FRD).

Aim

This study tests the hypothesis that OS markers levels in cord blood may predict the onset of FRD pathologies.

Patients and methods

168 preterm newborns of GA: 24-32 weeks (28.09 ± 1.99); and BW: 470-2480 gr (1358.11 ± 454.09) were consecutively recruited. Markers of potential OS risk (non-protein bound iron, NPBI; basal superoxide anion, BSA; under stimulation superoxide anion, USSA) and markers of OS-related damage (total hydroperoxides, TH; advanced oxidation protein products, AOPP) were assessed in cord blood. Associations between FRD onset and OS markers were checked through inferential analysis (univariate logistic regression).

Results

The development of FRD was significantly associated to high cord blood levels of TH, AOPP and NPBI (respectively p = 0.000, OR = 1.025, 95%CI = 1.013-1.038; p = 0.014, OR = 1.092, 95%CI = 1.018-1.172; p = 0.007, OR = 1.26995%CI = 1.066-1.511).

Conclusions

Elevated levels of TH, AOPP and, above all, NPBI, in cord blood are associated with increased risk for FRD. OS markers allow the early identification of infants at risk for FRD because of perinatal oxidant exposure. This can be useful in devising strategies to prevent or ameliorate perinatal outcome.     

Family functioning, burden and parenting stress 2 years after very preterm birth

Background

Examining rates of difficulties in family functioning following very preterm birth has been a relatively neglected area of research.

Aims

To examine family functioning, burden and parenting stress in families with very preterm compared with term born children, and investigate influences of parental mental health problems and child neurodevelopmental disability on family outcomes in families with preterm children.

Study design

Participants were 184 very preterm and 71 term children and their parents. Parents completed the Family Assessment Device, Parenting Stress Index and Impact on Family questionnaires when their children were 2 years old (corrected for prematurity). Parental mental health and social risk information were also collected. Children were assessed for neurodevelopmental disability.

Results

Families with very preterm children reported poorer family functioning (p = .03) compared with families with term born children, with less evidence for differences between families with very preterm and term born children in parenting stress and family burden. Within very preterm families, parental mental health problems were associated with higher levels of parenting stress (p = .001), and parents of children with a neurodevelopmental disability were more likely to report higher family burden (p = .04).

Conclusions

For families with very preterm children, parental mental health symptoms and child neurodevelopmental disability may identify families at risk of greater stress and burden who may benefit from additional support.     

Placental pathology and neurological morbidity in preterm infants during the first two weeks after birth

Background

The placenta plays a crucial role during pregnancy and dysfunction causes long-term neurological problems. Identifying placenta-related risks for neurological problems shortly after birth may provide clues for early interventions aiming to improve neurological outcome.

Objective

To determine the association between placental pathology and neurological morbidity in preterm infants during the first two weeks after birth.

Study design

Placentas of 52 singleton, preterm infants (GA: 25–31 weeks, BW: 560–2250 grammes) were examined for histopathology. The infants' neurological condition shortly after birth was determined by assessing the quality of their general movements (GMs): normal, abnormal, or hypokinetic, on days 5, 8, and 15. A motor optimality score (MOS) was also assigned.

Results

Examination of the placentas revealed maternal vascular underperfusion (n = 29), ascending intrauterine infection (AIUI) (n = 19), villitis of unknown aetiology (n = 6), chronic deciduitis (n = 11), foetal thrombotic vasculopathy (FTV) (n = 9), and elevated nucleated red blood cells (NRBCs) as a marker for foetal hypoxia (n = 7). None of the placental lesions were significantly associated with the quality of GMs or MOS.

Conclusions

This study indicated that placental lesions were not associated with infants' neurological condition as measured by the quality of their general movements during the first two weeks after birth.     

General movements in infants born from mothers with early-onset hypertensive disorders of pregnancy in relation to one year's neurodevelopmental outcome

Background:

Assessment of general movements (GMs) at three months is considered useful for prediction of adverse neurological outcome in high risk infants.

Aims:

To study the prevalence of abnormal GMs in infants born from women with early-onset hypertensive disorders of pregnancy and the association of GMs with neurodevelopmental outcome at one year.

Study design:

Prospective study, part of a randomised controlled trial of pre-birth management strategies.

Subjects:

Infants born from women with early-onset hypertensive disorders of pregnancy.

Outcome measures:

GMs observation and neurological examination at term and three months corrected age; at one year neurological examination and Bayley Scales of Infant Development.

Results:

From 216 women included, 175 of 178 surviving infants (mean gestational age 31.6 weeks [SD 2.3], mean birth weight 1346 grams [SD 458]), were examined at three months. At term age normal, mildly abnormal and definitely abnormal GMs were observed in 54%, 36% and 10% respectively; and at three months in 47%, 40% and 13%. Mildly or definitely abnormal GMs at three months were not associated with abnormal neurological examination at one year, however, they were associated with delayed psychomotor development at one year (p = 0.01).

Conclusions

In this prospective study, including small for gestational age, preterm infants about half of them did not have normal GMs at term and three months. There was no association of GMs at term nor three months with neurological outcome at one year, but there was a significant association of GMs at three months with one year psychomotor development.     

Functional impairments at school age of preterm born children with late-onset sepsis

Background

Late-onset sepsis is a relatively common complication particularly of preterm birth that affects approximately a quarter of very low birth weight infants.

Aim

We aimed to determine the motor, cognitive, and behavioural outcome at school age of preterm children with late-onset sepsis compared to matched controls.

Study design and subjects

A prospective case-control study that included preterm infants (gestational age < 32 weeks and/or birth weight < 1500 g) admitted to our Neonatal Intensive Care Unit in 2000-2001 with a culture-proven late-onset sepsis, and controls matched for gestational age.

Outcome measures

At school age we assessed motor skills, intelligence, visual perception, visuomotor integration, verbal memory, attention, executive functioning, and behaviour.

Results

At 6-9 years, 21 of 32 children with late-onset sepsis (68%) had borderline or abnormal motor outcome with most problems in fine motor skills. Their total IQ was 89 compared to 98 in controls. In addition, verbal memory and attention were affected compared to controls (0.61 standard deviations (SD), 95% confidence interval (CI) 0.04-1.17, p = 0.033 and 0.94 SD, 95% CI 0.32-1.62, p = 0.011, respectively). Multiple episodes of sepsis and gram-negative sepsis were risk factors for worse cognitive outcome.

Conclusions

At school age, a majority of preterm children with late-onset sepsis had motor problems. Their IQ was considerably lower than matched controls, and memory and attention were specifically impaired. Outcome at school age of preterm children with late-onset sepsis was worse than previously thought.     

Myocardial function in offspring 5-8years after pregnancy complicated by preeclampsia

Introduction

Preeclampsia and diabetic pregnancies share pathophysiological features suggested to influence epigenetic changes during foetal life with importance for later development and metabolic and cardiovascular diseases.

Aim

Our objective was to study the myocardium in offspring after pregnancy complications.

Methods

Forty-five children (age 5-8 years) delivered from pregnancies complicated by preeclampsia (n = 25), diabetes mellitus type 1 (n = 8) or gestational diabetes mellitus (n = 12) were included. Fifteen children from uneventful pregnancies served as controls. Myocardial functions of right and left ventricle were examined by conventional Doppler and tissue Doppler imaging (TDI).

Results

No major differences were found in the myocardial function between offspring of pregnancy complications and control group. However, the preeclampsia group had smaller hearts, increased heart rate and increased late diastolic velocity (A′-wave) at mitral valve attachments shown by both pulsed wave and colour TDI compared to the control and diabetic groups together (p ≤ 0.01).

Conclusion

Children born after preeclampsia may show effects of a negative impact on the heart already at the age of 5 to 8 years. The numbers of examined children were, however, limited.     

Parenting stress in mothers of preterm infants during early infancy

Objective

Mothers of preterm infants during the first year of life may experience stresses greater that those found in mothers of term infants. The aim of the study was to determine the levels of parenting stress and psychological well-being in mothers of very preterm babies in comparison to a control group of term mothers.

Methods

One hundred and five mothers who delivered 124 babies at ≤ 30 weeks gestation were recruited together with 105 mothers who delivered 120 babies at term. At 4 months of age (corrected for prematurity for the preterm babies), the mothers completed the Parenting Stress Index Short Form, the Edinburgh Postnatal Depression Scale (EPDS), the Dyadic Adjustment Scale (DAS) and the Short Temperament Scale for Infants (STSI). The preterm and term groups were compared.

Results

Questionnaires were returned from 86 of the preterm mothers and 97 of the term mothers. The mean Total Stress score for the preterm and term groups was 67.0 and 63.79 respectively (P = 0.32) with 17% of the preterm and 9% of the term group having high scores (P = 0.135). There were no differences of the EPDS and the DAS between the groups. The temperament of the preterm infants was similar to the term infants. For both groups, scores on the EPDS, DAS and the STSI were independent predictors of Total Stress scores on multiple regression analysis.

Conclusion

Parenting stress in mothers of preterm infants during early infancy does not appear to be greater than that in mothers of infants born at term. For both groups of mothers, depression symptoms, marital satisfaction and infant temperament were independent risk factors for high levels of parenting stress.     

Reduced cerebellar diameter in very preterm infants with abnormal general movements

Background

Abnormal General Movements (GMs) early in life are predictive of later neuromotor deficits and are related to white matter abnormalities on magnetic resonance imaging (MRI). However, other structural correlates of abnormal GMs have not been defined.

Aims

The objective of this study was to explore brain-metrics (linear brain measurements on MRI representative of 3-D brain volumes) at term as a predictor of abnormal GMs at 1 and 3 months' corrected age in preterm infants. It was hypothesized that abnormal GMs would be related to reduced brain-metrics in primary motor areas, namely the cerebellum and parietal lobes.

Study design

Eighty three preterm infants (< 30 weeks' gestational age) were scanned at term-equivalent age. MRI was assessed for white matter abnormality and brain-metrics in six predefined brain regions (i.e. bifrontal, biparietal, lateral ventricles and transverse cerebellar diameters, and inter-hemispheric distance).

Outcome measures

At 1 and 3 months' corrected age infants' GMs were assessed from video-taped footage and rated as normal or abnormal using standardized methodology.

Results

At 1 month, 63% (n = 52) of infants had abnormal GMs with no association between any of the brain-metrics and abnormal GMs. At 3 months, 23% (n = 18) of infants had abnormal GMs (absent fidgety movements n = 18; abnormal fidgety movements n = 0). Reduced bifrontal, biparietal, and cerebellar transverse diameters, along with an increase in lateral ventricle sizes were associated with an increased risk of abnormal GMs at 3 months' corrected age. After controlling for white matter abnormality and grade III/IV intraventricular haemorrhage, only the cerebellar transverse diameter was predictive of abnormal GMs at 3 months.

Conclusions

Reduced cerebellar diameter at term equivalent age is related to abnormal GMs at 3 months' corrected age, independent of white matter abnormality and intraventricular haemorrhage.     

Transcutaneous bilirubinometry is not influenced by term or skin color in neonates

Background

The utility of transcutaneous bilirubin measurements (TcB) in screening for hyperbilirubinemia in preterm infants (< 34 weeks) and in non-white infants remains a matter of debate.

Aim

To evaluate accuracy of TcB in preterm and term infants of different ethnic backgrounds, using a second generation bilirubinometer.

Study design

The Draeger JM-103® device was used to measure TcB. Eighty five measurements of TcB and total serum bilirubin (TSB) were retrospectively compared. Neonates were stratified into groups according to gestational age: < 34 weeks (group 1, n = 44) and > 34 weeks (group 2, n = 41), and according to ethnic origin: Caucasians (group A, n = 49) and non-Caucasians (group B, n = 36).Statistical analysis, using Pearson's correlation coefficient (r) and Bland–Altman analysis were performed to evaluate correlation and agreement between TSB and TcB values. Multiple linear regression was used to control for confounders for TSB values.

Results

Correlation between TSB and TcB was high. Pearson's correlation coefficients were over 0.9 in all groups (0.910, 0.908, 0.916 and 0.934, p < 0.0001 in groups 1, 2, A, and B respectively). Bland–Altman plots showed acceptable and close limits of agreements (56.8/− 57.7, 54.2/− 67.2, 57.7/− 55.8, and 51.3/− 69.9 μmol/L in groups 1, 2, A and B respectively) with a trend for TcB to overestimate TSB in groups 2 and B. Birth term and skin color were not identified as confounding factors for predicting TSB in multiple linear regression.

Conclusions

TcB measurements using the Draeger JM-103® device correlate significantly with TSB, regardless of term and skin color. Transcutaneous bilirubinometry seems to be a safe and cost-effective screening method for severe hyperbilirubinemia in newborns of different terms and ethnic origins.     

Sodium Alginate (Gaviscon®) does not reduce apnoeas related to gastro-oesophageal reflux in preterm infants

Background

Apnoea of prematurity (AOP) frequently recurs in preterm infants. We have previously shown that a significant but variable proportion of AOP is induced by gastro-oesophageal reflux (GOR).

Aim

The aim of this study is to evaluate the efficacy of sodium alginate in reducing the frequency of GOR-related AOP.

Subjects

Twenty-eight preterm infants with AOP were studied by a six-hour recording of combined multichannel intraluminal impedance and pH monitoring and polysomnography, including two three-hour postprandial periods: sodium alginate was given after one single meal named as drug-given (DG) meal, while the other as drug-free (DF).

Results

During 165 h of registration, 715 apnoeas were recorded, 368 after-DG and 347 after-DF (p = .99); furthermore, 851 GOR episodes were detected, 315 after-DG and 536 after-DF (p = .001). No differences in the number of AOP were found between DG and DF. A significant reduction in the number of acid GORs and in acid exposure was found during DG, while the administration of sodium alginate didn't influence non-acid GOR indexes. The frequency of GOR-related apnoeas didn't differ between DG and DF.

Discussion

Sodium alginate doesn't reduce the total number of AOP nor GOR-related apnoeas. On the other hand, it reduces acid GOR features, while it had no effect on non-acid GOR indexes.     

Perinatal cerebral insults alter auditory event-related potentials

Background

Auditory event-related potentials (AERPs) can be used as indices of neural information processing. Altered AERPs have been reported in children and young adults with frontal lobe infarction.

Aim

To test the hypothesis that perinatal brain injury affects cortical auditory processing.

Methods

We assessed AERPs at term, 6 and 12 months of age in preterm infants [n = 9, median gestational age (GA) 27.9, range 23.9-30.0 wk], term infants with perinatal intracerebral hemorrhage (ICH) [n = 5, GA 40.3, range 37.4-42.3 wk], and term infants with perinatal asphyxia [n = 4, GA 39.4, range 37.9-40.3 wk]. Healthy preterm (n = 16) and term infants (n = 22) served as controls. A harmonic tone of 500-Hz frequency was used as standard and of 750-Hz as deviant stimulus. Mean AERP amplitudes were calculated over 100 ms periods from 50 to 350 ms. The developmental outcome was followed until 2 years of age.

Results

The term ICH (p = 0.012) and asphyxia (p = 0.0016) group had smaller or more negative responses to the deviant, resulting in smaller or more negative MMR amplitudes than those of the controls. The preterm ICH group did not differ significantly from their preterm born controls. MMR varied in all patient groups and was not associated with adverse outcome.

Conclusion

AERP alterations suggest that perinatal cerebral insults affect cortical auditory processing.     

Endothelial progenitor cells, bronchopulmonary dysplasia and other short-term outcomes of extremely preterm birth

Aim

To evaluate the impact of endothelial progenitor cells (EPCs), a subset of committed circulatory stem cells, on the development of bronchopulmonary dysplasia (BPD) and other short term outcomes in a cohort of extremely premature newborns.

Methods

Progenitor cells were quantified by flow cytometry at birth in 36 neonates born <=28 weeks of gestation and at 36 postmenstrual weeks in 18 of them. Cells expressing the stemness markers CD34, CD133, or both were defined as circulating progenitor cells (CPCs). EPCs were defined as CPCs co-expressing the endothelial marker KDR.

Results

Mean (SD) gestational age and birth weight of the infants studied were 26.2(1.5) weeks and 761.6(171.8) grams, respectively. EPC levels at birth did not differ between infants who subsequently developed BPD (n = 9) and those who did not (n = 24) [CD34⁺KDR⁺ EPCs: 81(34-41) vs 80(56-110), p = 0.7] and were not correlated with the duration of mechanical ventilation or O2-dependence, nor with the need of surfactant replacement. Infants with a hemodynamically significant patent ductus arteriosus (PDA) (n = 22) had significantly lower EPC levels at birth than those with no PDA (n = 11) [CD34⁺KDR⁺ cells: 47(34-92) vs 142(84.5-221), p = 0.008]. Data from the 18 infants studied both at birth and at 36 postmenstrual weeks showed that, while CPCs sharply decline over time, levels of all EPCs phenotypes are preserved after delivery.

Conclusions

Levels of EPCs at birth did not affect the risk of developing BPD in our group of extremely premature neonates. However, the association between low EPC counts at birth and PDA may be clinically relevant, and deserves further studies.     

Cardiovascular and metabolic outcome in 6-8 year old offspring of women with type 1 diabetes with near-optimal glycaemic control during pregnancy

Background

High maternal glucose concentrations during diabetic pregnancy may lead to health problems in the offspring later in life. We showed in a previous nationwide study on pregnancy outcome in type 1 diabetic women that prepregnancy care was good and a near-optimal glycaemic control during pregnancy was achieved (mean HbA1c 6.2%).

Aims

We investigated to what extent current care and treatment of pregnant women with type 1 diabetes were related to cardiovascular and metabolic disturbances in the offspring at school age. Additionally, we studied the influence of level of maternal glycaemic control, preterm birth and neonatal macrosomia (birth weight > p90).

Study design

Observational cohort study.

Subjects

6-8 year old offspring of women with type 1 diabetes (ODM, n = 213) and a control group of children of non-diabetic women (n = 79).

Outcome measures

BMI, blood pressure, parameters of fasting glucose regulation and lipid metabolism, components of the metabolic syndrome (overweight, hypertension, impaired fasting glucose, dyslipidaemia).

Results

Parameters of fasting glucose regulation and lipid metabolism and the frequency of components of the metabolic syndrome did not significantly differ between ODM and controls. Systolic blood pressure was slightly higher in ODM. The influence of level of maternal glycaemic control, preterm birth and neonatal macrosomia on outcome in ODM was limited.

Conclusions

Current care and treatment of pregnant women with type 1 diabetes result in cardiovascular and metabolic outcome in the offspring at 6-8 years of age that is comparable to that in children of non-diabetic women. Further follow-up should substantiate these results at later age.