Mothers seeing their VLBW infants within 3 h after birth are more likely to establish a secure attachment behavior: evidence of a sensitive period with preterm infants?

OBJECTIVE: Close contact of mother and child in the first hours after birth is essential for the establishment of a secure attachment behavior in term infants. To date, studies investigating whether a 'sensitive period' also exists for very low birth weight (VLBW) preterm infants are lacking. STUDY DESIGN: Attachment patterns of 62 VLBW infants were assessed using the 'strange situation' setting and correlated with the time mothers saw their child for the first time. Furthermore, maternal and infant covariates possibly influencing the attachment behavior were analyzed. As maternal factors the mother's age, social status and pregnancy history were recorded and at three time points (time 1, 2 and 3 (t-1, t-2 and t-3)), a semi-structured interview, a depression and a social support questionnaire were performed. As infant factors neonatal basic data, ventilation time and length of hospital stay were recorded. Disease severity was scored using the clinical risk index for babies, score for neonatal acute physiology (SNAP), SNAP perinatal extension and nursery neurobiological risk score. At time points t-2 and t-3, the infants were examined using the second edition of Bayley scales of infant development. RESULTS: In all, 53.2% of the children showed a secure, 33.9% an insecure-avoidant, 3.2% an insecure-ambivalent and 9.7% an insecure-disorganized attachment behavior. Preterm infants whose mothers had seen them within 3 h after birth had a higher rate of secure attachment than preterm infants with no early contact (76 versus 41%, P=0.009). Firstborns showed a significantly higher rate of insecure attachment behavior (93 versus 67%, P=0.01). No influence on attachment behavior was shown for any other maternal or infant factor. CONCLUSIONS: Our results support the hypothesis that the first hours after birth are a 'sensitive period' for the development of attachment behavior in VLBW infants. When a mother is enabled to see her infant shortly after birth, the 'sensitive period' right after birth may be used to help forming an important basis for the secure attachment of the preterm infant.

Stem cells in pediatric heart failure.

Pediatric heart failure could be a target for regenerative therapy. Stem cell-based therapy has the potential to provide functional cardiomyocytes. Whereas adult stem cells have shown no or only minimal therapeutic benefit in adults with no evidence of transdifferentiation, embryonic stem cells can differentiate to any cell type, including cardiomyocytes. However, ethical concerns and immunological problems are associated with embryonic stem cells derived from the inner cell mass of blastocysts. Recently, somatic cells could be reprogrammed to a pluripotent state (i.e. induced pluripotent stem cells) with the help of transcription factors. This technique removes ethical and probably also immunological concerns. Nevertheless extensive experimental research will be necessary before cell replacement strategies become clinically applicable. Because the underlying pathophysiology differs significantly with age, caution is warranted extrapolating data obtained in experimental models of cardiac ischemia and clinical studies in adults to the pediatric population. Pediatric heart failure has a good prognosis if causal therapy is possible. However, some forms of congenital heart disease and especially dilated cardiomyopathy still have limited therapeutic options. Almost half of children with symptomatic cardiomyopathy receive a transplant or die within two years. The authors will review the relevant stem cell sources for cell-based treatments. And, given the differences of the underlying diseases between adult and pediatric patients with heart failure, it is contemplated which condition of pediatric patients with heart failure is most likely to benefit and which cell type would be appropriate.

Transcatheter closure of symptomatic aortopulmonary window in an infant.

An aortopulmonary window is a rare congenital cardiac defect. In the majority of symptomatic neonates and infants, primary surgical repair is the treatment of choice. In selected infants, catheter closure of the defect with a device may be feasible. We report on the successful closure of an AP window in a 12 month old infant, using a 6mm Amplatzer septal occluder. The procedure and follow-up were uneventful.

Factors influencing apnea and bradycardia of prematurity - implications for neurodevelopment.

BACKGROUND: Apnea and bradycardia of prematurity (ABP) are possible risks towards damage of the developing brain. OBJECTIVES: To characterize the influence of neonatal factors on ABP and to determine the relationship of ABP to neurodevelopmental outcome. METHODS: ABP was described in very low birth weight infants (n = 83) using the frequency and severity of ABP episodes with a clinical score considering heart rate, oxygenation, duration and interventions performed during each episode. Neonatal factors were analyzed for their relationship to ABP using regression analysis. Neurodevelopment was investigated using the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II at a corrected age of 13 months. Power of ABP parameters to predict outcome was assessed by logistic regression analysis. RESULTS: ABP typically started within the first week after birth. Spontaneous resolution occurred at a postmenstrual age (PMA) of 36.0 +/- 2.2 (31.1-44.1) weeks. A delayed resolution (>36 weeks PMA) and a higher average daily ABP score during a defined developmental period (31-37 weeks PMA) were associated with a higher incidence of unfavorable outcome (MDI or PDI <69 or death). CONCLUSION: ABP is an age-specific phenomenon. However, more severe courses than expected for PMA or the resolution at a later PMA indicated an increased risk of neurodevelopmental disturbances at a corrected age of 13 months.

[Pain management and coping behaviour in premature babies (< 1500 g) at corrected age of 36 months influence of neonatal experience and maternal anxiety]. / Schmerzverhalten und Bewältigungsformen von Frühgeborenen (< 1500g) im korrigierten Alter von 36 Monaten -- Einflüsse neonataler Erfahrungen und mütterlicher Angste.

INTRODUCTION: Neonatal experience of pain and distress can lead to developmental problems, which can be associated with long-term emotional and behavioural disorders. The aim of the study was to analyse the effects of early experiences of pain and maternal reactions on the pain and coping behaviour of preterm infants. METHODS: In a prospective longitudinal study of 69 very low birth weight (VLBW) preterm infants, neonatal data regarding painful manipulations, analgesics and sedatives, and general medical condition (Nursery Neurobiological Risk Score; NBRS) were assessed. At the (corrected) age of 36 months, 53 preterm infants and a control group of 23 full-term infants were re-examined. Pain and coping behaviour were estimated by a questionnaire. Maternal anxiety was assessed in semi-structured interviews at the age of 3, 12 and 36 months in the preterm group. RESULTS: The mean gestational age was 29 + 0 weeks (23 + 3 to 34 + 1), the mean birth weight 1058 g (380 to 1480 g) in preterms and 39 + 3 weeks (37 + 0 to 42 + 0) and 3379 g (2400 to 4130 g), respectively, for the full-terms. The sex ratio was equal, 45.3 % of the preterms were multiples (controls 34.8 %). Preterms had higher descriptive scores for all types of pain situations. After controlling for other associated factors, a negative correlation between birth weight and later pain behaviour in medical situations remained. Preterms had a more negative coping behaviour during every day injuries. In terms of coping behaviour, only a shorter inpatient treatment in the neonatal period was associated with social withdrawal after controlling for other associated factors. Maternal anxiety at the age of 12 and 36 months was associated with negative coping behaviour following simple injuries. CONCLUSIONS: While preterms do not have a higher pain threshold in general, a subgroup does have a higher risk for later sensation to pain. Preterms use more unfavourable coping strategies in simple injuries which, in turn, seem to be decisively mediated by maternal anxiety. Future research should focus on psycho-social factors involved in the development of pain reactions, as these can predispose towards behavioural disorders.

Transhepatic approach for catheter interventions in infants and children with congenital heart disease.

UNLABELLED: We report on our experience with transhepatic access for catheter interventions in six children (age range 2.5 months-9 years). Three had systemic venous anomalies, and one infant a femoral venous occlusion. In two further patients with bradyarrhythmia after a Fontan operation with an intraatrial Gore-Tex tunnel, transhepatic access was chosen to achieve a perpendicular orientation of the transseptal needle to the atrial baffle, allowing puncture of the Gore-Tex membrane. Two of the patients underwent ablation of an accessory pathway; in one an atrial septal defect was closed. A 2.5 month old baby after Norwood I operation, underwent balloon dilation of the pulmonary arteries. Two patients after prior Fontan surgery underwent DDDR pacemaker implantation. The size of the introducer sheath ranged from 4 F up to two 9 F introducers in the same vein for pacemaker insertion. At the end of the procedure, hemostasis was achieved by external compression. RESULTS: Transhepatic access could be established in all six patients (using a mirror image approach in children with left atrial isomerism) and the interventional procedures could be performed as planned. In one patient with implantation of a permanent pacemaker, a subcutaneous hematoma occurred, requiring blood transfusion. CONCLUSION: In selected pediatric patients, transhepatic access for catheter intervention can easily be achieved.

[Electrical heart diseases--therapy during childhood and adolescence]. / Elektrische Herzerkrankungen--Behandlung im Kindes- und Jugendalter.

With increasing experience, radiofrequency catheter ablation of tachyarrhythmia substrates has become first choice therapy for children >4 years of age with recurrent tachyarrhythmia. In younger patients, the risks associated with the procedure (typically procedure-related AV block or possible coronary artery damage) have to be weighed against the natural history of the tachyarrhythmia substrate, and the degree of control achieved with pharmacologic agents. Ablation for postoperative arrhythmias is more complicated, and associated with lower success rates and a higher rate of recurrence (of the same or a new tachyarrhythmia) despite acute procedural success. In this setting, catheter ablation has to be considered in conjunction with further surgery or the use of a defibrillator as a backup device to prevent arrhythmia-related sudden death. Also in inherited arrhythmias as in long QT syndrome and Brugada syndrome, implantable defibrillators have to be considered as a possible therapeutic option for patients with a higher risk for sudden cardiac death, irrespective of age.

[Mother-infant Interactions with Very Low Birth Weight multiple newborns (< 1500 g). A comparison of mother-multiple and mother-single births]. / Mutter-Kind-Interaktion bei sehr leichtgewichtig frühgeborenen Mehrlingen (< 1500 g). Ein Vergleich von Mutter-Mehrlings- und Mutter-Einlings-Dyaden.

BACKGROUND: Assisted reproductive techniques and fertility enhancing therapies have increased the rate of multiple births and, therefore, the risk of prematurity. Our hypothesis is that mothers of preterm multiples are less able to provide such enhancing interactions than mothers of preterm singletons, resulting in a developmental disadvantage for preterm twins and triplets. PATIENTS AND METHODS: Of 77 very low birth weight preterms (VLBW) who were examined prospectively with their mothers in a longitudinal study, 35 were multiples and 42 were singletons. At a corrected age of three months the quality of the mother-infant interaction with multiples vs. singletons was examined. The Mannheim Rating System, a 40-item standardized observation instrument based on a 10 minute videotaped sequence of interaction, was used. RESULTS: The analyses showed several differences between mother-singleton and mother-multiple interactions. Mothers of multiples were less stimulating and reactive and showed less babytalk. Multiple infants were also less reactive than singletons. In mother-multiple dyads there were less verbal exchanges between mother and child. CONCLUSIONS: There are definite differences in mother-multiple compared to mother-singleton interactions, so that VLBW multiples may be at even greater risk for negative mother-infant interactions than singletons.

[The effect of biological and psychosocial factors on maternal distress and coping in the first months after preterm delivery of an infant weighing less than 1500 g]. / Die Bedeutung biologischer und psychosozialer Einflussfaktoren für das Belastungs- und Bewältigungserleben bei Müttern Frühgeborener < 1500 g in den ersten Lebensmonaten des Kindes.

PROBLEM: Several studies have shown that maternal coping after a premature birth has an influence on the psychosocial development of preterm infants. As maternal coping is so important for development of premature infants, in this prospective study the medical state of the child, previous negative experiences, personal and partnership resources and social support outside the family were examined regarding their effects on maternal distress and coping after preterm birth. SAMPLE, MATERIAL, METHODS: 63 of 68 consecutive mothers with a preterm infant weighing less than 1500 g were examined with a semistructured interview and questionnaires (F-Sozu, ADS-L, FPI-R) at the time of discharge. RESULTS: 30.2 % (n = 19) of the mothers had multiples. The mean gestational age of the infants was 28 + 4 weeks (23 + 3 to 34 + 1 weeks), the mean birthweight was 1035 g (380 -1480 g). Although many mothers had fears concerning a handicap of their child, not medical complications per se influenced the mothers perception, but the duration of the medical treatment. Previous distressing experiences through complications of previous pregnancies and deliveries, as well as handicaps, chronic disorders and behavior problems of siblings influenced the perception of the child's health negatively, if they have had an effect on the current pregnancy. The mother's mood was not associated with the perception of the child's health, but with the atmosphere of the intensive care unit, partnership resources and social support outside the family. CONCLUSIONS: As both biological and psychosocial factors had an effect on the mother's experiences, it is necessary to evaluate previous maternal experiences and coping resources and offer practical counselling for the mothers to optimize the clinical care in the future.

Prediction of hemorrhagic transformation after thrombolytic therapy of clot embolism: an MRI investigation in rat brain.

BACKGROUND AND PURPOSE: Thrombolytic treatment of stroke carries the risk of hemorrhagic transformation. Therefore, the potential of MRI for prediction of recombinant tissue plasminogen activator (rtPA)-induced bleeding is explored to identify patients in whom rtPA treatment may provoke such complications. METHODS: Spontaneously hypertensive rats (SHR) (n=9) were submitted to middle cerebral artery (MCA) clot embolism, followed 3 hours later by intra-arterial infusion of 10 mg/kg rtPA. Untreated SHR (n=9) were infused with saline. MRI imaging was performed before treatment and included apparent diffusion coefficient (ADC), T2, and perfusion mapping and contrast enhancement with gadolinium-DTPA. The distribution of intracerebral hemorrhages was studied 3 days later by histological staining. RESULTS: Clot embolism led to the rapid decline of ADC in the territory of the occluded artery. Tissue lesion volume derived from ADC imaging increased by 155+/-69% in the untreated animals and by 168+/-87% in the treated animals (P=NS), determined on the histological sections after 3 days. This same lesion growth in both groups indicated absence of therapeutic effect after 3-hour treatment delay. Hemorrhagic transformations were significantly more frequent in treated SHR (P<0.05). In untreated rats, hemorrhages were found in the border zone of the ischemic territory; in treated animals, hemorrhagic transformations occurred in the ischemic core region. rtPA-induced hemorrhages were predicted by a disturbance of the blood-brain barrier in 3 of 4 animals before treatment by Gd-DTPA contrast enhancement but not by ADC, T2, or perfusion imaging. The region of contrast enhancement colocalized with subsequent bleeding in these animals. CONCLUSIONS: The disturbance of blood-brain barrier but not of other MR parameters allows risk assessment for hemorrhagic transformation induced by subsequent thrombolytic treatment.

Dynamic changes of ADC, perfusion, and NMR relaxation parameters in transient focal ischemia of rat brain.

The potential of multiparametric MRI parameters for differentiating between reversibly and irreversibly damaged brain tissue was investigated in an experimental model of focal brain ischemia in the rat. The middle cerebral artery (MCA) was occluded by intraluminal suture insertion for 60 or 90 min, followed by 4.5 h of reperfusion. The apparent diffusion coefficient (ADC) of brain water, T(1) and T(2) relaxation times, and CBF(i), an MR-derived index of cerebral perfusion, were repeatedly measured and correlated with the outcome from the ischemic impact. A novel user-independent approach for segmentation of ADC maps into classes of increasing injury was introduced to define regions of interest (ROIs) in which these parameters were evaluated. MCA occlusion led to a graded decline of ADC, which corresponded with both the severity of flow reduction and an increase in T(1) and T(2) relaxation times. Removal of the suture led to a triphasic restitution of blood flow consisting of a fast initial rise, a secondary decline, and final normalization. Postischemic reperfusion led to a rise of ADC irrespective of the duration of ischemia. However, the quality of recovery declined with increasing severity of the ischemic impact. Throughout the observation time, T(1) and T(2) showed a continuous increase, the intensity of which correlated with the severity of ADC decline during ischemia. Particularly with longer ischemia time, elevated T(2) in combination with reduced ADC yielded a lower probability of recovery during recirculation, while intraischemic perfusion information contributed less to the prediction of outcome. In conclusion, the combination of MR parameters at the end of ischemia correlated with the probability of tissue recovery but did not permit reliable differentiation between reversibly and irreversibly damaged tissue.

Magnetic resonance prediction of outcome after thrombolytic treatment.

Treatment of clinical stroke with recombinant tissue plasminogen activator (rt-PA) carries the risk of hemorrhagic complications. Hence, predictors of therapeutic outcome with respect to (a) reperfusion and (b) tissue recovery would be very useful to identify potentially salvageable brain tissue. Magnetic resonance (MR) parameters, especially the apparent diffusion coefficient of water (ADC), perfusion-weighted imaging (PWI) and T(2) relaxometry are thought to provide this information. We evaluated the prognostic implications of ADC, PWI and T(2) relaxometry immediately before initiation of thrombolytic treatment in a model of clot embolism in rats. Animals (n = 14) were treated with intraarterial rt-PA (10 mg/kg) at 90 min after embolism. MR imaging was repeatedly performed at 4.7 T before and up to 5.5 h after embolism. ADC was calculated from diffusion-weighted images (b-values: 30, 765, 1500 s/mm(2)), arterial spin tagging was used for PWI, and quantitative T(2) relaxometry was performed with a Carr-Purcell-Meiboom-Gill (CPMG) sequence. A reperfusion index was calculated to assess the quality of thrombolytic recanalization. The decline of ADC at the end of the experiment to below 80% of control was defined as unfavorable outcome. The probability of tissue injury at the end of the experiments increased with the severity of ADC changes before the initiation of treatment (probability of unfavorable outcome: 21%, 44%, 65% for ADC values of 80-90%, 70-80% and <70% of control, respectively). Pretreatment PWI or T(2) relaxometry also correlated with outcome but-alone or in combination with pretreatment ADC maps-did not improve injury prediction over that obtained by ADC alone. Outcome was influenced positively by successful reperfusion the quality of which, however, could not be predicted by pre-treatment MR characteristics. The data demonstrate that ADC mapping performed before the initiation of thrombolytic treatment provides reliable risk assessment of impeding brain injury but due to uncertainties of postischemic reperfusion does not allow precise outcome prediction in individual experiments.

Treatment with an endothelin type A receptor-antagonist after cardiac arrest and resuscitation improves cerebral hemodynamic and functional recovery in rats.

OBJECTIVE: Successful resuscitation of the brain after cardiac arrest requires unimpaired microcirculatory reperfusion. Postischemic cerebral hypoperfusion presumably is mediated through activation of endothelin type A receptors (ET(A)). The effect of the selective ET(A) antagonist BQ123 on cerebral blood flow and function was studied in a rat model of cardiac arrest. DESIGN: Prospective, randomized trial. SETTING: Experimental animal laboratory. SUBJECTS: Twelve male Sprague-Dawley rats (290-350 g). INTERVENTIONS: Cardiac arrest for 12 mins was induced by electrical fibrillation of the heart, followed by standardized cardiopulmonary resuscitation. BQ123 (0.8 mg/kg; n = 6) or its vehicle (saline; n = 6) was injected intravenously at 15 mins after the return of spontaneous circulation. MEASUREMENTS: Cortical blood flow was measured by laser-Doppler flowmetry, electrophysiological function by recording the amplitude of somatosensory evoked potentials, vascular reactivity by ventilation with 6% CO2, and the functional coupling of blood flow by recording the laser-Doppler flow (LDF) changes during somatosensory stimulation. Hemodynamic and functional cerebral recovery was monitored for 3 hrs after the return of spontaneous circulation. MAIN RESULTS: Forty-five minutes after the return of spontaneous circulation, postischemic hypoperfusion developed in both groups, as reflected by a decrease of the LDF signal to about 60% of the preischemic level. In untreated animals, hypoperfusion persisted throughout the observation time, but in animals receiving BQ123, LDF gradually returned to normal. CO2 reactivity in untreated animals was severely reduced for 2-3 hrs after the onset of recirculation, whereas after BQ123 treatment it returned to normal and after 2 hrs even above normal. The ET(A) antagonist also induced a more rapid recovery of the somatosensory evoked potentials amplitude and of the functional blood flow response to somatosensory stimulation, but these parameters did not recover completely within the observation period. CONCLUSIONS: Application of the ET(A) antagonist BQ123 during the early reperfusion period after cardiac arrest shortens postischemic cerebral hypoperfusion and accelerates the restoration of the cerebrovascular CO2 reactivity and the recovery of electrophysiologic function.

Probability of metabolic tissue recovery after thrombolytic treatment of experimental stroke: a magnetic resonance spectroscopic imaging study in rat brain.

The effect of thrombolytic therapy on metabolic changes was studied in rats submitted to thromboembolic stroke. Reperfusion was initiated at three different time points, 1.5, 3, and 4.5 hours after embolism (n = 3 each), by injection of recombinant tissue-type plasminogen activator (rt-PA). Recovery was observed during 5 hours of reperfusion using perfusion-weighted images and a two-dimensional 1H magnetic resonance spectroscopic imaging (MRSI) technique. Temporal evolution of the cerebral metabolites lactate and N-acetyl-aspartate (NAA) was determined. To analyze the chances of metabolic tissue recovery, the outcome of treatment, defined by a reversal of lactate concentration, was compared with the lactate intensity before treatment. In untreated animals (n = 4), clot embolism resulted in a drop of perfusion signal intensity in the occluded hemisphere followed by an increase of lactate concentration and a decrease of NAA that persisted throughout the observation period. Thrombolysis partially restored blood flow, but the mean lactate concentration decreased only slightly after successful lysis in animals treated 1.5 hours after embolism. If treatment was initiated later, no decline of lactate level was observed. Five hours after initiation of thrombolysis, the average tissue lactate amounted to 95 +/- 6, 111 +/- 17, and 139 +/- 60% of the early ischemic value (40 minutes after embolization) if treatment began 1.5, 3, and 4.5 hours after embolism, respectively. The NAA level declined slightly but never showed a recovery after rt-PA treatment. In individual pixels, the probability of metabolic tissue recovery clearly declined with increasing lactate concentration before thrombolysis. Interestingly, this probability was independent of treatment delay, but the number of pixels with low lactate declined with increasing ischemia time. Potential clinical applications of MRSI include monitoring of therapeutic intervention as well as support for prognosis of outcome after rt-PA treatment.

Brain hemorrhages after rt-PA treatment of embolic stroke in spontaneously hypertensive rats.

Intracerebral hemorrhage is a major complicating factor of thrombolytic therapy of stroke. To investigate the incidence of bleeding in animals with a diseased vascular system, thrombolysis was carried out in spontaneously hypertensive rats (SHR) after clot embolism of the right middle cerebral artery (MCA). Three hours after embolism SHR were treated with either recombinant tissue-plasminogen activator (rt-PA) or saline, and neurological deficits and intracerebral hemorrhages were evaluated after 3 days survival. Rt-PA-treated SHR exhibited a significantly higher incidence of hemorrhages than untreated rats but neurological deficits and survival rates showed a non-significant trend for improvement. This model offers the possibility of investigating the pathophysiology of post-thrombolytic complications in a clinically relevant small animal model.

Gradient echo time dependence and quantitative parameter maps for somatosensory activation in rats at 7 T.

The dependence of functional magnetic resonance imaging (MRI) contrast on the gradient echo time TE in T2*-weighted blood oxygenation level-dependent (BOLD) fast low-angle shot (FLASH) imaging has been studied at 7 T for electrical forepaw stimulation in alpha-chloralose anesthetized rats. The observed variation of both the activation signal intensity and spatial pattern with echo time TE, resulting from the regional heterogeneity of T2*, was assessed by the calculation of quantitative T2* and quantitative STE = 0 maps, the latter representing the back-extrapolated signal intensity for TE = 0. The subsequently determined T2* and STE = 0 activation maps allowed a pixelwise separation of true BOLD from inflow contributions to forepaw stimulation-induced signal change in the somatosensory cortex of rat brain. For functional activation experiments performed with one single echo time the prior measurement of a quantitative T2* map is recommended as minimum further information to judge the intensity and the regional pattern of the resulting activation maps.