Effects of perinatal stress and maternal traumatic stress on the cortisol regulation of preterm infants.

Preterm infants experience intense stress during the perinatal period because they endure painful and intense medical procedures. Repeated activation of the hypothalamic-pituitary-adrenal (HPA) axis during this period may have long-term effects on subsequent cortisol regulation. A premature delivery may also be intensely stressful for the parents, and they may develop symptoms of posttraumatic stress disorder (PTSD). Usable saliva samples were collected (4 times per day over 2 days, in the morning at awakening, at midday, in the afternoon, and in the evening before going to bed) to assess the diurnal cortisol regulation from 46 preterm infants when the infants were 12 months of corrected age (∼ 14 months after birth). Mothers reported their level of PTSD symptoms. The results showed an interaction between perinatal stress and maternal traumatic stress on the diurnal cortisol slope of preterm infants (R(2) = .32). This suggests that the HPA axis of preterm infants exposed to high perinatal stress may be more sensitive to subsequent environmental stress.

Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe.

The aim of this study is to quantify the prevalence and types of rare chromosome abnormalities (RCAs) in Europe for 2000-2006 inclusive, and to describe prenatal diagnosis rates and pregnancy outcome. Data held by the European Surveillance of Congenital Anomalies database were analysed on all the cases from 16 population-based registries in 11 European countries diagnosed prenatally or before 1 year of age, and delivered between 2000 and 2006. Cases were all unbalanced chromosome abnormalities and included live births, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. There were 10,323 cases with a chromosome abnormality, giving a total birth prevalence rate of 43.8/10,000 births. Of these, 7335 cases had trisomy 21,18 or 13, giving individual prevalence rates of 23.0, 5.9 and 2.3/10,000 births, respectively (53, 13 and 5% of all reported chromosome errors, respectively). In all, 473 cases (5%) had a sex chromosome trisomy, and 778 (8%) had 45,X, giving prevalence rates of 2.0 and 3.3/10,000 births, respectively. There were 1,737 RCA cases (17%), giving a prevalence of 7.4/10,000 births. These included triploidy, other trisomies, marker chromosomes, unbalanced translocations, deletions and duplications. There was a wide variation between the registers in both the overall prenatal diagnosis rate of RCA, an average of 65% (range 5-92%) and the prevalence of RCA (range 2.4-12.9/10,000 births). In all, 49% were liveborn. The data provide the prevalence of families currently requiring specialised genetic counselling services in the perinatal period for these conditions and, for some, long-term care.

Fetal Diagnosis of Cardiac Rhabdomyoma, its Management and Outcome : P71

Objectives: This study analyses the long term cardiac and neurological outcome of patients with cardiac rhabdomyoma (CR) in order to allow comprehensive prenatal counselling. Because of the relative rarity of the disease, there is paucity of data concerning the outcome of patients with CR. Methods: A retrospective study including all cases with echocardiographic diagnosis of CR encountered between April 1986 and August 2006. Results: Of 24 CR patients identified, 7 were diagnosed in-utero at a gestational age (GA) between 28-35 weeks and 17 postnatally between 10 days and 5 years. 14 had multiple CR and 10 had one/two CR. The CRs were situated predominantly in the LV (70%), RV (52%) and IVS (48%) and to a lesser extent in the atria (13%) and pericardium (4%). Follow-up echocardiography in. 18'show\'ld complete postnatal regression of CR in 3, partial regression in 13 and no change in 2. Cardiac complications were encountered in 5 patients, 1 with WPW syndrome and SVT requiring anti-arrhythmic therapy, 1 with sub-aortic obstruction needing surgical intervention and 3 with occasional bouts of paroxysmal SVT. Long-term follow-up revealed tuberous sclerosis of Bourneville (TSB) as definite diagnosIs in 22 (92%), complicated by epilepsy in 16 (67%) and developmental delay in 14 (64%). Conclusions: CR generally regresses after birth and after the high risk perinatal period cardiac related problems are rare. The relatively poor neurodevelopmental outcome of the almost always associated TSB however should form a dominating aspect of the prenatal counselling of parents whose fetuses are diagnosed with this rare disease.

Cardiac and neurologic outcome of cardiac rhabdomyoma considerations for prenatal counseling

Abstract : Cardíac rhabdomyomas are benign cardiac tumors with few cardiac complications but with a known association to tuberous sclerosis that affects the neurologic outcome of the patients. Thís study analyses the long-term cardiac and neurological outcome of patients with cardiac rhabdomyomas in order to allow comprehensive prenatal counseling. qll prenatal and postnatal cases with echocardiographic diagnosis of cardiac rhabdomyomas encountered from August 1982 -September 2007 have been recorded. Independent factors, such às the number and the location of the tumors, have been analyzed for association with a diagnosis of tuberous sclerosis, in order to predict the cardiac and neurologic outcome of the patients. Cardiac complications include arrhythmias, outflow tract obstruction, secondary cardiogenic shock. Arrhythmias are the most often encountered problems during the neonatal period. Supraventricular tachycardia is the commonest rhythm disturbance identified. However, no specific dimension or location of the cardiac rhabdomyomas may predict the rhythm disturbances. The importance of the diagnosis of tuberous sclerosis in patients presenting with cardiac rhabdomyomas is exemplified by the neurodevelopmental complications showing 80% of cases with epilepsy and 63% of cases with a delayed development. The presence of multiple cardiac tumors in patients suggests a higher risk to be affected by tuberous sclerosis, compared to patients with a single tumor. Cardiac rhabdomyomas generally regress aftér birth and after the perinatal period cardiac-related problems are rare, but tuberous sclerosis and the associated neurodevelopmental complications dominate the clinical picture and should form an important aspect of the prenatal counseling of parents. Résumé : Les rhabdomyomes cardiaques sont des tumeurs cardiaques bénignes avec toutefois des complications. cardiaques possibles et surtout avec une association pour la sclérose tubéreuse de Bourneville qui détermine le pronostic neurologique. Cette étude présente une analyse du suivi cardiologique. et neurologique à long terme d'enfants avec un diagnostic de rhabdomyomes cardiaques dans le but de mieux informer les parents lors de la consultation anténatale. L'ensemble des cas de rhabdomyomes cardiaques diagnostiqués au moyen de l'échocardiographie pendant la période anténatale ainsi que postnatale a été répertorié d'août 1982 à septembre 2007. Des facteurs indépendants, tels que le nombre et la localisation des tumeurs, ont été analysés pour leur association avec le diagnostic de la sclérose tubéreuse de Bourneville, afin de prédire le pronostic cardiaque et neurologique de ces patients. Les complications cardiaques retrouvées sont les arythmies, les obstructions des voies d'éjection ventriculaire et le choc cardiogène secondaire. Les arythmies sont les problèmes les plus fréquemment rencontrés pendant la période néonatale.. La tachycardie supraventriculaire est le trouble de rythme le plus souvent identifié. Néanmoins, il n'y a pas de dimension ou de localisation.- spécifique d'un rhabdomyome cardiaque qui pourrait prédire ces troubles du rythme. L'importance de l'association au diagnostic de la sclérose tubéreuse de Bourneville chez les patients atteints de rhabdomyomes est démontrée à travers les complications du développement neurologique avec une attéinte épileptique dans 80% des cas ainsi qu'un retard de développement dans 63% des cas. La présence de multiples tumeurs cardiaques chez un patient suggère un risque accru d'être atteint de la sclérose tubéreuse de Bourneville comparé à un patient atteint d'une tumeur unique. Les rhabdomyomes cardiaques régressent après la naissance et après la période périnatale les complications cardiaques deviennent rares. Toutefois, l'association à la sclérose tubéreuse de Bourneville domine le tableau clinique avec des complications au niveau du développement neurologique et formé donc un aspect important lors de la consultation anténatale.

Differential responses of newborn pulmonary arteries and veins to atrial and C-type natriuretic peptides.

Atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are important dilators of the pulmonary circulation during the perinatal period. We compared the responses of pulmonary arteries (PA) and veins (PV) of newborn lambs to these peptides. ANP caused a greater relaxation of PA than of PV, and CNP caused a greater relaxation of PV than of PA. RIA showed that ANP induced a greater increase in cGMP content of PA than CNP. In PV, ANP and CNP caused a similar moderate increase in cGMP content. Receptor binding study showed more specific binding sites for ANP than for CNP in PA and more for CNP than for ANP in PV. Relative quantitative RT-PCR for natriuretic peptide receptor A (NPR-A) and B (NPR-B) mRNAs show that, in PA, NPR-A mRNA is more prevalent than NPR-B mRNA, whereas, in PV, NPR-B mRNA is more prevalent than NPR-A mRNA. In conclusion, in the pulmonary circulation, arteries are the major site of action for ANP, and veins are the major site for CNP. Furthermore, the differences in receptor abundance and the involvement of a cGMP-independent mechanism may contribute to the heterogeneous effects of the natriuretic peptides in PA and PV of newborn lambs.

Nuclear and cytoplasmic triiodothyronine-binding sites in primary sensory neurons and Schwann cells: radioautographic study during development.

The effects of the thyroid hormones on target cells are mediated through nuclear T3 receptors. In the peripheral nervous system, nuclear T3 receptors were previously detected with the monoclonal antibody 2B3 mAb in all the primary sensory neurons throughout neuronal life and in peripheral glia at the perinatal period only (Eur. J. Neurosci. 5, 319, 1993). To determine whether these nuclear T3 receptors correspond to functional ones able to bind T3, cryostat sections and in vitro cell cultures of dorsal root ganglion (DRG) or sciatic nerve were incubated with 0.1 nM [125I]-labeled T3, either alone to visualize the total T3-binding sites or added with a 10(3) fold excess of unlabeled T3 to estimate the part due to the non-specific T3-binding. After glutaraldehyde fixation, radioautography showed that the specific T3-binding sites were largely prevalent. The T3-binding capacity of peripheral glia in DRG and sciatic nerve was restricted to the perinatal period in vivo and to Schwann cells cultured in vitro. In all the primary sensory neurons, specific T3-binding sites were disclosed in foetal as well as adult rats. The detection of the T3-binding sites in the nucleus indicated that the nuclear T3 receptors are functional. Moreover the concomitant presence of both T3-binding sites and T3 receptors alpha isoforms in the perikaryon of DRG neurons infers that: 1) [125I]-labeled T3 can be retained on the T3-binding 'E' domain of nascent alpha 1 isoform molecules newly-synthesized on the perikaryal ribosomes; 2) the alpha isoforms translocated to the nucleus are modified by posttranslational changes and finally recognized by 2B3 mAb as nuclear T3 receptor. In conclusion, the radioautographic visualization of the T3-binding sites in peripheral neurons and glia confirms that the nuclear T3 receptors are functional and contributes to clarify the discordant intracellular localization provided by the immunocytochemical detection of nuclear T3 receptors and T3 receptor alpha isoforms.

Considerations for prenatal counselling of patients with cardiac rhabdomyomas based on their cardiac and neurologic outcomes.

Cardiac rhabdomyomas are benign cardiac tumours with few cardiac complications, but with a known association to tuberous sclerosis that affects the neurologic outcome of the patients. We have analysed the long-term cardiac and neurological outcomes of patients with cardiac rhabdomyomas in order to allow comprehensive prenatal counselling, basing our findings on the records of all patients seen prenatally and postnatally with an echocardiographic diagnosis of cardiac rhabdomyoma encountered from August, 1982, to September, 2007. We analysed factors such as the number and the location of the tumours to establish their association with a diagnosis of tuberous sclerosis, predicting the cardiac and neurologic outcomes for the patients.Cardiac complications include arrhythmias, obstruction of the ventricular outflow tracts, and secondary cardiogenic shock. Arrhythmias were encountered most often during the neonatal period, with supraventricular tachycardia being the commonest rhythm disturbance identified. No specific dimension or location of the cardiac rhabdomyomas predicted the disturbances of rhythm.The importance of the diagnosis of tuberous sclerosis is exemplified by the neurodevelopmental complications, with four-fifths of the patients showing epilepsy, and two-thirds having delayed development. The presence of multiple cardiac tumours suggested a higher risk of being affected by tuberous sclerosis. The tumours generally regress after birth, and cardiac-related problems are rare after the perinatal period. Tuberous sclerosis and the associated neurodevelopmental complications dominate the clinical picture, and should form an important aspect of the prenatal counselling of parents.

Considerations for prenatal counselling of patients with cardiac rhabdomyomas based on their cardiac and neurologic outcomes.

Cardiac rhabdomyomas are benign cardiac tumours with few cardiac complications, but with a known association to tuberous sclerosis that affects the neurologic outcome of the patients. We have analysed the long-term cardiac and neurological outcomes of patients with cardiac rhabdomyomas in order to allow comprehensive prenatal counselling, basing our findings on the records of all patients seen prenatally and postnatally with an echocardiographic diagnosis of cardiac rhabdomyoma encountered from August, 1982, to September, 2007. We analysed factors such as the number and the location of the tumours to establish their association with a diagnosis of tuberous sclerosis, predicting the cardiac and neurologic outcomes for the patients.Cardiac complications include arrhythmias, obstruction of the ventricular outflow tracts, and secondary cardiogenic shock. Arrhythmias were encountered most often during the neonatal period, with supraventricular tachycardia being the commonest rhythm disturbance identified. No specific dimension or location of the cardiac rhabdomyomas predicted the disturbances of rhythm.The importance of the diagnosis of tuberous sclerosis is exemplified by the neurodevelopmental complications, with four-fifths of the patients showing epilepsy, and two-thirds having delayed development. The presence of multiple cardiac tumours suggested a higher risk of being affected by tuberous sclerosis. The tumours generally regress after birth, and cardiac-related problems are rare after the perinatal period. Tuberous sclerosis and the associated neurodevelopmental complications dominate the clinical picture, and should form an important aspect of the prenatal counselling of parents.

Prematurity, maternal stress and mother-child interactions.

OBJECTIVE: Previous studies have shown that premature birth and the immaturity of the child can affect the quality of the parent-child relationship. The present study examines the relationship between maternal and infant interactional behavior over time and infant perinatal risk factors as well as maternal perinatal recollected traumatic experience. Few studies have explored the relationship between maternal stress and the quality of parent-infant interaction. DESIGN: Mother-child interaction was recorded at 6 and 18 months of infant's age, in a population of 47 preterm infants (GA<34 weeks) and 25 full-term infants, born in 1998, during a play interaction. According to the Care Index, sensitivity, control and unresponsiveness have been used to code maternal interactional characteristics, and cooperation, compliance-compulsiveness, difficulty and passivity have been used to code the infant's interactional characteristics. The level of maternal stress was evaluated with the Perinatal Posttraumatic Stress Disorder Questionnaire (PPQ), and the infant's perinatal risk factors were assessed with the Perinatal Risk Inventory (PERI). RESULTS: Mothers of high-risk infants, as well as mothers that had experienced traumatic stress in the perinatal period, were less sensitive and more controlling at 6 months. The interactional behavior of the preterm infant was different from that of the full-term infant at 18 months of age, and was correlated with maternal traumatic stress but not with perinatal risk factors. CONCLUSION: These results underline the importance of maternal traumatic experience related to premature birth and its potential long lasting influence on mother-child interactional behavior.

Impact of Early-Life Exposures on Immune Maturation and Susceptibility to Disease.

Exiting from the largely sterile environment of the womb, the neonatal immune system is not fully mature, and thus neonatal immune cells must simultaneously mount responses against environmental stimuli while maturing. This dynamic process of immune maturation is driven by a variety of cell-intrinsic and extrinsic factors. Recent studies have focused on some of these factors and have shed light on the mechanisms by which they drive immune maturation. We review the interactions and consequences of immune maturation during the pre- and perinatal period. We discuss environmental signals in early life that are needed for healthy immune homeostasis, and highlight detrimental factors that can set an individual on a path towards disease. This early-life period of immune maturation could hold the key to strategies for setting individuals on trajectories towards health and reduced disease susceptibility.

Prevalence at Birth of Cleft Lip With or Without Cleft Palate: Data From the International Perinatal Database of Typical Oral Clefts (IPDTOC).

As part of a collaborative project on the epidemiology of craniofacial anomalies, funded by the National Institutes for Dental and Craniofacial Research and channeled through the Human Genetics Programme of the World Health Organization, the International Perinatal Database of Typical Orofacial Clefts (IPDTOC) was established in 2003. IPDTOC is collecting case-by-case information on cleft lip with or without cleft palate and on cleft palate alone from birth defects registries contributing to at least one of three collaborative organizations: European Surveillance Systems of Congenital Anomalies (EUROCAT) in Europe, National Birth Defects Prevention Network (NBDPN) in the United States, and International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) worldwide. Analysis of the collected information is performed centrally at the ICBDSR Centre in Rome, Italy, to maximize the comparability of results. The present paper, the first of a series, reports data on the prevalence of cleft lip with or without cleft palate from 54 registries in 30 countries over at least 1 complete year during the period 2000 to 2005. Thus, the denominator comprises more than 7.5 million births. A total of 7704 cases of cleft lip with or without cleft palate (7141 livebirths, 237 stillbirths, 301 terminations of pregnancy, and 25 with pregnancy outcome unknown) were available. The overall prevalence of cleft lip with or without cleft palate was 9.92 per 10,000. The prevalence of cleft lip was 3.28 per 10,000, and that of cleft lip and palate was 6.64 per 10,000. There were 5918 cases (76.8%) that were isolated, 1224 (15.9%) had malformations in other systems, and 562 (7.3%) occurred as part of recognized syndromes. Cases with greater dysmorphological severity of cleft lip with or without cleft palate were more likely to include malformations of other systems.

Perinatal arrhythmias.

Cardiac arrhythmias are very frequent in fetuses and newborns. The prognosis depends on the nature of the arrhythmias but is most often either spontaneously benign or following short-term medication administration. A correct diagnosis is essential for both management and prognosis. It is based on echocardiography during the fetal period and mainly on history, physical exam, and electrocardiogram after birth, but other modalities are available to record transient arrhythmic events. Irregular rhythms are mostly benign and rarely require therapy. In most fetuses and infants, tachyarrhythmias resolve spontaneously or require short-term administration of antiarrhythmics. Approximately one third of these may recur later on, especially during adolescence. Persistent bradyarrhythmias might require pacemaker implantation when associated with failure to thrive or with risk of sudden death. CONCLUSION: Arrhythmias in fetuses and infants are very common and mostly benign. History, physical exam, and recording of the arrhythmia are essential to make a correct diagnosis and establish an appropriate management for the rare potentially harmful arrhythmias.

Congenital heart defects in Europe: prevalence and perinatal mortality, 2000 to 2005.

BACKGROUND: This study determines the prevalence of Congenital Heart Defects (CHD), diagnosed prenatally or in infancy, and fetal and perinatal mortality associated with CHD in Europe. METHODS AND RESULTS: Data were extracted from the European Surveillance of Congenital Anomalies central database for 29 population-based congenital anomaly registries in 16 European countries covering 3.3 million births during the period 2000 to 2005. CHD cases (n=26 598) comprised live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly (TOPFA). The average total prevalence of CHD was 8.0 per 1000 births, and live birth prevalence was 7.2 per 1000 births, varying between countries. The total prevalence of nonchromosomal CHD was 7.0 per 1000 births, of which 3.6% were perinatal deaths, 20% prenatally diagnosed, and 5.6% TOPFA. Severe nonchromosomal CHD (ie, excluding ventricular septal defects, atrial septal defects, and pulmonary valve stenosis) occurred in 2.0 per 1000 births, of which 8.1% were perinatal deaths, 40% were prenatally diagnosed, and 14% were TOPFA (TOPFA range between countries 0% to 32%). Live-born CHD associated with Down syndrome occurred in 0.5 per 1000 births, with > 4-fold variation between countries. CONCLUSION: Annually in the European Union, we estimate 36 000 children are live born with CHD and 3000 who are diagnosed with CHD die as a TOFPA, late fetal death, or early neonatal death. Investing in primary prevention and pathogenetic research is essential to reduce this burden, as well as continuing to improve cardiac services from in utero to adulthood.

Perinatal assessment of infant, parents, and parent-infant relationship: prematurity as an example.

This article reviews the stresses for parents, infants, and other caregivers during the period surrounding the birth of the premature infant. Principles of assessment of infant discomfort, parental stress, the parent-infant relationship, and the match of the medical caregiving environment to the individual infant's needs are discussed. Relevant tools to aide in these aspects of assessment are reviewed. The role of early assessment as preventive intervention and the indication for subsequent intervention in complicated cases of premature infants and their parents are further discussed. The article offers detailed clinical examples to illustrate these and other points throughout.

Prognostic value of early MR imaging in term infants with severe perinatal asphyxia.

The prognostic significance of magnetic resonance imaging (MRI) in the neonatal period was studied prospectively in 43 term infants with perinatal asphyxia. MRI was performed between 1 and 14 days after birth with a high field system (2.35 Tesla). Neurodevelopmental outcome was assessed by a standardized neurological examination and the Griffiths developmental test at a mean age of 18.9 months. The predictive value of the various MRI patterns was as follows: Severe diffuse brain injury (pattern AII+III; n = 7) and lesions of thalamus and basal ganglia (pattern C; n = 5) were strongly associated with poor outcome and greatly reduced head growth. Mild diffuse brain injury (pattern AI; n = 7), parasagittal lesions (B; n = 7), periventricular hyperintensity (D; n = 2), focal brain necrosis and hemorrhage (E; n = 3) and periventricular hypointense stripes (on T2-weighted images; F; n = 3) led in one third of the infants to minor neurological disturbances and mild developmental delay. Infants with normal MRI findings (G; n = 9) developed normally with the exception of one infant who was mildly delayed at 18 months. The results indicate that MRI examination during the first two weeks of life is of prognostic significance in term infants suffering from perinatal asphyxia. Severe hypoxic-ischemic brain lesions were associated highly significantly with poor neuro-developmental outcome, whereas infants with inconspicuous MRI developed normally.