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This review article focuses on neonatal respiratory physiology, mechanical ventilation of the neonate and changes induced by anesthesia and surgery. Optimal ventilation techniques for preterm and term neonates are discussed. In summary, neonates are at high risk for respiratory complications during anesthesia, which can be explained by their characteristic respiratory physiology. Especially the delicate balance between closing volume and functional residual capacity can be easily disturbed by anesthetic and surgical interventions resulting in respiratory deterioration. Ventilatory strategies should ideally include application of an 'open lung strategy' as well avoidance of inappropriately high VT and excessive oxygen administration. In critically ill and unstable neonates, for example, extremely low-birthweight infants surgery in the neonatal intensive care unit might be an appropriate alternative to the operating theater. Best respiratory management of neonates during anesthesia is a team effort that should involve a joint multidisciplinary approach of anesthetists, pediatric surgeons, cardiologists, and neonatologists to reduce complications and optimize outcomes in this vulnerable population., (© 2013 John Wiley & Sons Ltd.)

Development of the cardiovascular system through the last trimester of pregnancy and the subsequent neonatal period is profound. Morphological changes within the myocardium make the heart vulnerable to challenges such as fluid shifts and anesthetic drugs. The sensitivity of the myocardium to metabolic challenges and potential harm of drugs needed to maintain adequate blood pressure and cardiac output are highlighted. Traditional monitoring under anesthesia has focussed on maintaining oxygenation and heart rate in the neonate with less attention paid to blood pressure, cardiac output, and more importantly organ well-being. There is now a better understanding of the limitations of blood pressure homeostasis in the neonate and the potential consequences of marginal hypoperfusion. This article highlights some of these vulnerabilities particularly as they relate to anesthesia and surgery in the very young., (© 2013 John Wiley & Sons Ltd.)

Numerosity discrimination has been demonstrated in newborns, but not in fetuses. Fetal magnetoencephalography allows non-invasive investigation of neural responses in neonates and fetuses. During an oddball paradigm with auditory sequences differing in numerosity, evoked responses were recorded and mismatch responses were quantified as an indicator for auditory discrimination. Thirty pregnant women with healthy fetuses (last trimester) and 30 healthy term neonates participated. Fourteen adults were included as a control group. Based on measurements eligible for analysis, all adults, all neonates, and 74% of fetuses showed numerical mismatch responses. Numerosity discrimination appears to exist in the last trimester of pregnancy.

In the first year of life, infants possess two cognitive systems encoding numerical information: one for processing the numerosity of sets of 4 or more items, and the second for tracking up to 3 objects in parallel. While a previous study showed the former system to be already present a few hours after birth, it is unknown whether the latter system is functional at this age. Here, we adapt the auditory-visual matching paradigm that previously revealed sensitivity to large numerosities to test sensitivity to numerosities spanning the range from 2 to 12. Across studies, newborns discriminated pairs of large numerosities in a 3:1 ratio, even when the smaller numerosity was 3 (3 vs. 9). In contrast, newborn infants failed to discriminate pairs including the numerosity 2, even at the same ratio (2 vs. 6). These findings mirror the dissociation that has been reported with older infants, albeit with a discontinuity situated between numerosities 2 and 3. Two alternative explanations are compatible with our results: either newborn infants have a separate system for processing small sets, and the capacity of this system is limited to 2 objects; or newborn infants possess only one system to represent numerosities, and this system either is not functional or is extremely imprecise when it is applied to small numerosities., (© 2013 John Wiley & Sons Ltd.)

Neonatal anesthesia is fraught with potential risk for the patient and stress for the anesthesiologist. Where possible, recognition of these risks, avoidance of, and being able to manage them appropriately, must impact positively on perioperative outcomes in this vulnerable group of patients. Good communication with the parents, as well as with other healthcare providers, is crucial to safe and successful anesthetic care., (© 2013 John Wiley & Sons Ltd.)

Neonates are the most vulnerable age group in terms of anesthetic risk and perioperative mortality, especially in the developing world. Prematurity, malnutrition, delays in presentation, and sepsis contribute to this risk. Lack of healthcare workers, poorly maintained equipment, limited drug supplies, absence of postoperative intensive care, unreliable water supplies, or electricity are further contributory factors. Trained anesthesiologists with the skills required for pediatric and neonatal anesthesia as well as basic monitoring equipment such as pulse oximetry will go a long way to improve the unacceptably high anesthetic mortality., (© 2013 John Wiley & Sons Ltd.)

Ensuring adequate oxygenation of the developing brain is the cornerstone of neonatal critical care. Despite decades of clinical research dedicated to this issue of paramount importance, our knowledge and understanding regarding the physiology and pathophysiology of neonatal cerebral blood flow are still rudimentary. This review primarily focuses on currently available human clinical and experimental data on cerebral blood flow and autoregulation in the preterm and term infant. Limitations of systemic blood pressure values as surrogates for monitoring adequate cerebral oxygen delivery are discussed. Particular emphasis is placed on the high interindividual variability in cerebral blood flow values, vasoreactivity, and autoregulatory thresholds making the applications of normative values highly questionable. Technical and ethical difficulties to conduct such trials leave us with a near complete lack of knowledge on how pharmacological and surgical interventions impact on cerebral autoregulation. The ensemble of these works argues for the necessity of highly individualized care by taking advantage of continuous bedside monitoring of cerebral circulation. They also point to the urgent need for further studies addressing the exciting but difficult issue of cerebral blood flow autoregulation in the neonate., (© 2013 John Wiley & Sons Ltd.)

The physiology of the neonate is ideally suited to the transition to extrauterine life followed by a period of rapid growth and development. Intravenous fluids and electrolytes should be prescribed with care in the neonate. Sodium and water requirements in the first few days of life are low and should be increased after the postnatal diuresis. Expansion of the extracellular fluid volume prior to the postnatal diuresis is associated with poor outcomes, particularly in preterm infants. Newborn infants are prone to hypoglycemia and require a source of intravenous glucose if enteral feeds are withheld. Anemia is common, and untreated is associated with poor outcomes. Liberal versus restrictive transfusion practices are controversial, but liberal transfusion practices (accompanied by measures to minimize donor exposure) may be associated with improved long-term outcomes. Intravenous crystalloids are as effective as albumin to treat hypotension, and semi-synthetic colloids cannot be recommended at this time. Inotropes should be used to treat hypotension unresponsive to intravenous fluid, ideally guided by assessment of perfusion rather than blood pressure alone. Noninvasive methods of assessing cardiac output have been validated in neonates. More studies are required to guide fluid management in neonates, particularly in those with sepsis or undergoing surgery. A balanced salt solution such as Hartmann's or Plasmalyte should be used to replace losses during surgery (and blood or coagulation factors as indicated). Excessive fluid administration during surgery should be avoided., (© 2013 John Wiley & Sons Ltd.)

Background: The echocardiographic assessment of circulatory function in sick newborn infants has the potential to improve patient care. However, measurements are prone to error and have not been sufficiently validated. Phase-contrast magnetic resonance imaging (MRI) provides highly validated measures of blood flow and has recently been applied to the newborn population. The aim of this study was to validate measures of left ventricular output and superior vena caval flow volume in newborn infants., Methods: Echocardiographic and MRI assessments were performed within 1 working day of each other in a cohort of newborn infants., Results: Examinations were performed in 49 infants with a median corrected gestational age at scan of 34.43 weeks (range, 27.43-40 weeks) and a median weight at scan of 1,880 g (range, 660-3,760 g). Echocardiographic assessment of left ventricular output showed a strong correlation with MRI assessment (R(2) = 0.83; mean bias, -9.6 mL/kg/min; limits of agreement, -79.6 to +60.0 mL/kg/min; repeatability index, 28.2%). Echocardiographic assessment of superior vena caval flow showed a poor correlation with MRI assessment (R(2) = 0.22; mean bias, -13.7 mL/kg/min; limits of agreement, -89.1 to +61.7 mL/kg/min; repeatability index, 68.0%). Calculating superior vena caval flow volume from an axial area measurement and applying a 50% reduction to stroke distance to compensate for overestimation gave a slightly improved correlation with MRI (R(2) = 0.29; mean bias, 2.6 mL/kg/min; limits of agreement, -53.4 to +58.6 mL/kg/min; repeatability index, 54.5%)., Conclusions: Echocardiographic assessment of left ventricular output appears relatively robust in newborn infant. Echocardiographic assessment of superior vena caval flow is of limited accuracy in this population, casting doubt on the utility of the measurement for diagnostic decision making., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Objectives: This study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status., Methods: The first intestinal discharge (meconium) was collected from 23 newborns stratified by maternal diabetes status: 4 mothers had pre-gestational type 2 diabetes mellitus (DM) including one mother with dizygotic twins, 5 developed gestational diabetes mellitus (GDM) and 13 had no diabetes. The meconium microbiome was profiled using multi-barcode 16S rRNA sequencing followed by taxonomic assignment and diversity analysis., Results: All meconium samples were not sterile and contained diversified microbiota. Compared with adult feces, the meconium showed a lower species diversity, higher sample-to-sample variation, and enrichment of Proteobacteria and reduction of Bacteroidetes. Among the meconium samples, the taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the DM group showing higher alpha-diversity than that of no-diabetes or GDM groups. No global difference was found between babies delivered vaginally versus via Cesarean-section. Regression analysis showed that the most robust predictor for the meconium microbiota composition was the maternal diabetes status that preceded pregnancy. Specifically, Bacteroidetes (phyla) and Parabacteriodes (genus) were enriched in the meconium in the DM group compared to the no-diabetes group., Conclusions: Our study provides evidence that meconium contains diversified microbiota and is not affected by the mode of delivery. It also suggests that the meconium microbiome of infants born to mothers with DM is enriched for the same bacterial taxa as those reported in the fecal microbiome of adult DM patients.

Background and Objective: Therapeutic hypothermia is now the standard of care for hypoxic-ischemic encephalopathy. Treatment should be started early, and it is often necessary to transfer the infant to a regional NICU for ongoing care. There are no large studies reporting outcomes from infants cooled passively compared with active (servo-controlled) cooling during transfer. Our goal was to review data from a regional transport service, comparing both methods of cooling., Methods: This was a retrospective observational study of 143 infants referred to a regional NICU for ongoing therapeutic hypothermia. Of the 134 infants transferred, the first 64 were cooled passively, and 70 were subsequently cooled after purchase of a servo-controlled mattress. Key outcome measures were time to arrival at the regional unit, temperature at referral and arrival at the regional unit, and temperature stability during transfer., Results: The age cooling was started was significantly shorter in the actively cooled group (46 [0-352] minutes vs 120 [0-502] minutes; P <.01). The median (range) stabilization time (153 [60-385] minutes vs 133 [45-505] minutes; P = .04) and age at arrival at the regional unit (504 [191-924] minutes vs 452 [225-1265]) minutes; P = .01) were significantly shorter in the actively cooled group. Only 39% of infants passively cooled were within the target temperature range at arrival to the regional unit compared with 100% actively cooled., Conclusions: Servo-controlled active cooling has been shown to improve temperature stability and is associated with a reduction in transfer time.

Objective: To compare outcomes with trial of labor after cesarean (TOLAC) or elective repeat cesarean delivery on maternal request (ERCD-MR)., Design: Prospective cohort study., Setting: Danish university hospital., Population: Women with TOLAC (n = 1161) and women with ERCD-MR (n = 622) between 2003 and 2010. Exclusion criteria were diabetes, two prior cesarean sections, index cesarean at a different hospital, a delivery after the index cesarean, twin gestation, gestational age <37(+0)  weeks and stillbirth., Methods: Data were obtained from the Aarhus Birth Cohort database, which comprised prospective registration of the deliveries., Main Outcome Measures: Adverse neonatal outcomes, risk factors for emergency cesarean, and uterine rupture in case of TOLAC., Results: TOLAC was associated with an increased risk of neonatal depression [odds ratio (OR) 3.6, 95% confidence interval (CI) 1.1-19.1] and neonatal intensive care unit admission (adjusted OR 1.9, 95% CI 1.3-2.8). Within the TOLAC group 67% delivered vaginally. In the TOLAC group 1.3% (n = 15) of the women had a complete uterine rupture. None of these infants had sequelae after 12 months. Significant risk factors for emergency cesarean were no prior vaginal delivery (adjusted OR 1.8, 95% CI 1.1-3.0), index emergency cesarean during labor (adjusted OR 3.0, 95% CI 2.3-4.1), maternal age ≥35 years (adjusted OR 1.9, 95% CI 1.3-2.8), pre-pregnancy body mass index ≥30 (adjusted OR 2.1, 95% CI 1.3-3.3), and birthweight 4000-4499 g (adjusted OR 1.5, 95% CI 1.1-2.1). Uterine rupture was associated with the use of epidural analgesia (OR 2.2, 95% CI 1.1-4.9) and no prior vaginal delivery (p = 0.03)., Conclusion: TOLAC is an acceptable individualized option for women without major risk factors., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

The pediatric surgeon deals with a large number and variety of congenital defects in neonates that frequently involve early surgical intervention and care. Because the neonatal cardiac physiology is unique, starting with the transition from fetal circulation and including differences in calcium metabolism and myocardial microscopic structure and function, it serves the pediatric surgeon well to have a sound understanding of these principles and how they directly and indirectly affect their plans and treatments. In addition, many patients will have associated congenital heart disease that can also dramatically influence not only the surgical and anesthetic care but also the timing and planning of procedures. Finally, the pediatric surgeon is often called upon to treat conditions and complications associated with complex congenital heart disease such as feeding difficulties, bowel perforations, and malrotation in heterotaxy syndromes. In this article, we will review several unique aspects of neonatal cardiac physiology along with the basic physiology of the major groups of congenital heart disease to better prepare the training and practicing pediatric surgeon for care of these complex and often fragile patients., (© 2013 Published by Elsevier Inc.)

The transition from intrauterine to extrauterine life is a complex adaptation. Although, in a sense, the entire time in utero is in preparation for this transition, there are many specific anatomic and physiologic changes that take place in the weeks and days leading up to labor that facilitate a healthy transition. Some, including increasing pulmonary vasculature and blood flow, are part of an ongoing process of maturation. Others, such as a reversal in the lung from secreting fluid to absorbing fluid and the secretion of pulmonary surfactant, are associated with the hormonal milieu that occurs when spontaneous labor is impending. Interventions such as elective cesarean birth or induction of labor may interfere with this preparation for birth. Postnatal interventions such as immediate clamping of the umbilical cord and oropharyngeal suction may also compromise the normal process of newborn transition. This article reviews the physiology of the fetal to newborn transition and explores interventions that may facilitate or hinder the optimal process., (© 2013 by the American College of Nurse-Midwives.)

Evaluation of suspected endocrine pathology in newborn infants requires knowledge of the dynamic changes that characterize normal hormonal function in the neonatal period. This article reviews normal endocrine physiology as it pertains to common clinical scenarios encountered in neonatal surgical patients. Topics covered include thyroid and adrenal function as well as glucose and calcium metabolism., (© 2013 Published by Elsevier Inc.)

The neonatal intestine is a complex organ that regulates the absorption of nutrients essential for growth and development. Intestinal failure results from insufficient or functionally inadequate bowel and can lead to failure of neonatal growth and development. Current literature on neonatal intestinal physiology and failure was reviewed and summarized. A homeostatic interplay of electrolytes, enzymes, and hormonal regulators is essential to achieve the physiologic balance needed for adequate intestinal performance. Physiologic consequences of intestinal failure are dependent on the length and anatomic location of the diseased or surgically resected bowel. Intestinal failure leads to disruption of normal intestinal physiology and may have long-term consequences for growth and development if inadequately treated. Parenteral nutrition remains the mainstay of treatment for neonatal intestinal failure., (© 2013 Published by Elsevier Inc.)

Protecting the brain in vulnerable infants undergoing surgery is a central aspect of perioperative care. Understanding the link between blood flow, oxygen delivery, and oxygen consumption leads to a more informed approach to bedside care. In some cases, we need to consider how high we can let the partial pressure of carbon dioxide go before we have concerns about risk of increased cerebral blood volume and change in intracranial hydrodynamics. Alternatively, in almost all such cases, we have to address the question of how low can we let the blood pressure drop before we should be concerned about brain perfusion. This review provides a basic understanding of brain bioenergetics, hemodynamics, hydrodynamics, autoregulation, and vascular homeostasis to changes in blood gases, which is fundamental to our thinking about bedside care and monitoring., (© 2013 Published by Elsevier Inc.)

In the neonate, the liver is relatively immature and undergoes several changes in its functional capacity during the early postnatal period. The essential liver functions can be classified into three categories: metabolism, detoxification, and bile synthesis. In general, the immature liver function has limited consequences on the healthy term neonate. However, preterm neonates are particularly susceptible to the effects of the immature liver function placing them at risk of hypoglycemia, hyperbilirubinemia, cholestasis, bleeding, and impaired drug metabolism. An appreciation of the dynamic changes in liver function during the neonatal period is essential for successful management of neonates who require medical and surgical interventions. This review will focus on the neonatal liver function as well as the changes that the liver undergoes as it matures., (© 2013 Published by Elsevier Inc.)

Neonatal hematology is a complex and dynamic process in the pediatric population. Surgeons frequently encounter hematologic issues regarding hemostasis, inflammation, and wound healing. This publication provides a surgeon-directed review of hematopoiesis in the newborn, as well as an overview of the current understanding of their hemostatic profile under normal and pathologic conditions., (© 2013 Published by Elsevier Inc.)

Managing pulmonary issues faced by both term and preterm infants remains a challenge to the practicing pediatric surgeon. An understanding of normal fetal and neonatal pulmonary development and physiology is the cornerstone for understanding the pathophysiology and treatment of many congenital and acquired problems in the neonate. Progression through the phases of lung development and the transition to postnatal life requires a symphony of complex and overlapping events to work in concert for smooth and successful transition to occur. Pulmonary physiology and oxygen transport in the neonate are similar to older children; however, there are critical differences that are important to take into consideration when treating the youngest of patients. Our understanding of fetal and neonatal pulmonary physiology continues to evolve as the molecular and cellular events governing these processes are better understood. This deeper understanding has helped to facilitate groundbreaking research, leading to improved technology and treatment of term and preterm infants. As therapeutics and research continue to advance, a review of neonatal pulmonary physiology is essential to assist the clinician with his/her management of the wide variety of challenging congenital and acquired pulmonary disease., (© 2013 Published by Elsevier Inc.)

Background: Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies., Methods and Results: This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies. ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.5 mm [interquartile range, 6.1-7.1 mm]; tricuspid ring displacement in ART: 5.5 mm [interquartile range, 5.1-6.1]; P<0.001), impaired relaxation, and dilated atria (atrial area in controls, 1.46 cm(2) [interquartile range, 1.2-1.5 cm(2)]; atrial area in ART, 1.6 cm(2) [interquartile range, 1.3-1.8 cm(2)]; P<0.001). Additionally, ART infants showed persistence of most cardiac changes and a significant increase in blood pressure and aortic intima-media thickness (systolic blood pressure in controls, 74 mm Hg [interquartile range, 67-83 mm Hg]; systolic blood pressure in ART, 83 mm Hg [interquartile range, 75-94 mm Hg]; P<0.001; aortic intima-media thickness in controls, 0.52 mm [interquartile range, 0.45-0.56 mm]; aortic intima-media thickness in ART, 0.64 mm [interquartile range, 0.62-0.67]; P<0.001). We could not demonstrate that our findings were directly caused by ART because of their association with various confounding factors, including intrauterine growth restriction or factors related to the cause of infertility., Conclusions: Children conceived by ART manifest cardiac and vascular remodeling that is present in fetal life and persists in postnatal life, suggesting opportunities for early detection and potential intervention. The underlying mechanisms and the effect of potential confounders such as growth restriction or prematurity remain to be elucidated.

Unlabelled: Cardiac MRI in neonates holds promise as a tool that can provide detailed functional information in this vulnerable group. However, their small size, rapid heart rate, and inability to breath-hold, pose particular challenges that require prolonged high-contrast and high-SNR methods. Balanced-steady state free precession (SSFP) offers high SNR efficiency and excellent contrast, but is vulnerable to off-resonance effects that cause banding artifacts. This is particularly problematic in the blood-pool, where off-resonance flow artifacts severely degrade image quality., Methods: In this article, we explore active frequency stabilization, combined with image-based shimming, to achieve prolonged SSFP imaging free of banding artifacts. The method was tested using 2D multislice SSFP cine acquisitions on 18 preterm infants, and the functional measures derived were validated against phase-contrast flow assessment., Results: Significant drifts in the resonant frequency (165 ± 23Hz) were observed during 10-min SSFP examinations. However, full short-axis stacks free of banding artifacts were achieved in 16 subjects with stabilization; the cardiac output obtained revealed a mean difference of 9.0 ± 8.5% compared to phase-contrast flow measurements., Conclusion: Active frequency stabilization has enabled the use of prolonged SSFP acquisitions for neonatal cardiac imaging at 3T. The findings presented could have broader implications for other applications using prolong SSFP acquisitions., (Copyright © 2012 Wiley Periodicals, Inc.)

Drug dosing in infants should be based on their physiological characteristics and the pharmacokinetic and -dynamic profile of the compound. Since maturational physiological changes are most prominent in infancy, variability is the key feature of clinical pharmacology in infancy: developmental physiology drives developmental pharmacology. This is illustrated by the link between renal physiology and renal drug clearance and between hepatic physiology and hepatic drug elimination for some specific compounds. However, the maturational profiles of the individual elimination processes differ substantially at the enzyme and transporter level. This implies that it is important to integrate all ontogeny-related knowledge of the different elimination routes to predict compound specific, phenotypic in vivo observations of infancy. In addition to the introduction of already available in vivo observations to validate mechanistic (estimated to in vivo observations) or physiology based pharmacokinetic (PBPK, developmental physiology related estimated to in vivo observations) models, a simultaneous use of both approaches (mechanistic and PBPK) to search for discrepancies between both approaches may also unveil 'missing' links in maturational physiology or clinical pharmacology (e.g. ontogeny renal or hepatic drug transporters): developmental pharmacology drives developmental pharmacology., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

This is an autobiographical review describing the author's career in immunology research and summarizing his current understanding of the areas involved. Contributions to autoimmunity, immune deficiency, transfusion immunology, HLA-disease associations, reproductive immunology, cellular therapies, and innate immunity are included; also discussion of medical research ethics and various research-related activities., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To evaluate whether the timing of excessive maternal weight gain in a cohort of women following current guidelines for healthy living during pregnancy affects neonatal adiposity at birth., Methods: One hundred seventy-two healthy women who were at least 18 years old with body mass indexes (BMIs) of at least 18.5 were recruited between 16 weeks and 20 weeks of gestation. The cohort followed healthy living guidelines during pregnancy and were retrospectively grouped according to 2009 Institute of Medicine guidelines for weight gain in the first and second halves of pregnancy: 1) appropriate gestational weight gain (ie, within Institute of Medicine recommendations) in the first and second halves of pregnancy ("overall appropriate"); 2) appropriate gestational weight gain in the first half of pregnancy and excessive gestational weight gain in the second half of pregnancy ("late excessive"); 3) excessive gestational weight gain in the first half of pregnancy and appropriate gestational weight gain in the second half of pregnancy ("early excessive"); and 4) excessive gestational weight gain throughout pregnancy ("overall excessive"). Primary measures included neonatal weight, length, BMI, and body fat at birth measured 6-18 hours after delivery. Neonatal body fat greater than 14% was considered excessive., Results: Neonates of women who gained excessively in the first half of pregnancy exhibited greater heel-crown length, birth weight, and excessive body fat ("early excessive" 17.5±3.1%, "overall excessive" 18.7±3.3%) compared with those born to women who gained appropriately ("overall appropriate" 13.2±4.1%; "late excessive" 14.7±3.3%; P<.01). Neonates of women who gained excessively in the first half of pregnancy had an increased risk (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.35-5.17) of elevated body fat at birth compared with neonates of women with total excessive weight gain (OR 1.49, 95% CI 0.80-2.79)., Conclusion: Timing of excessive weight gain is an important factor influencing neonatal morphometrics. Prevention of early excessive weight gain should be encouraged in the period before conception and reinforced early in pregnancy., Level of Evidence: II.

Objective: We investigated whether newborn speech-sound discrimination can be studied in 40 min using fast multifeature mismatch negativity (MMN) paradigm and do the results differ from those obtained with the traditional oddball paradigm., Methods: Newborns' MMN responses to five types of changes (consonant identity, F0, intensity, vowel duration and vowel identity) were recorded in the multifeature group (N=15) and vowel duration and vowel identity changes in the oddball group (N=13), after which the MMNs from both groups were compared with each others., Results: Statistically significant MMNs in the 190-600 ms time range from the stimulus onset were found for most change types in both paradigms. Newborn MMN responses were predominantly positive but a small number of participants elicited negative MMNs instead. MMN amplitudes did not differ between the multifeature and oddball groups., Conclusions: Newborn speech-sound discrimination can be assessed in a short recording time using the fast multifeature paradigm., Significance: The paradigm presented here can be used to record extensive auditory discrimination profiles in newborns and assess development of speech-sound discrimination and its difficulties., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To review the current literature addressing the visualisation and clinical applicability of coronary artery blood flow in various foetal and neonatal settings., Method: We reviewed original research papers, commentaries and review articles which studied the usefulness of coronary flow assessments in the growth restricted foetus, healthy neonates and neonates with clinical conditions such as asphyxia, congenital heart disease and post-surgical duct ligation myocardial failure., Results: Relevant literature showed that visualisation of coronary blood flow in growth restricted foetuses is considered an ominous sign and identifies a subgroup of foetuses with a poorer foetal and neonatal outcome. A direct relationship between coronary blood flow and echocardiographic parameters in healthy term infants was noted. These assessments also provided useful information in infants with heart disease and perinatal asphyxia. Coronary perfusion has been noted as an important haemodynamic marker in the peri-operative evaluation of preterm infants undergoing surgical duct ligation., Conclusions: The available literature suggests that these assessments play an important role in improving the understanding of the underlying clinical physiology of the disease process in both the foetus and the newborn. Future research should focus on the evolution of coronary blood flow in clinical situations such as hypotension and inotropic support.

Moro response in healthy term newborns were studied to determine latency interval, time taken for optimal response (embracing movement of arms), and total duration of reflex response. Latency interval for onset of response was 0.41-0.49. Time taken for optimal response was 0.910-1.041s. Total duration of Moro response was 2.34 -2.59 s. Values were similar for males and females. Optimal response in babies born by cesarean section were significantly delayed than vaginal babies.

New parents should be aware that infants' sleep is unlike that of adults and that meeting their infant's needs is likely to disrupt their own sleep. They will need to adjust their routine to manage their own sleep needs. Parental sleep patterns in the postpartum period are tied to the infant's development of a circadian sleep-wake rhythm, and the infant's feeds. Close contact with the mother and exposure to light/dark cues appear to assist in the development of the infant's circadian rhythm. The composition of breastmilk varies over the course of 24 hours and some components produced at night are likely to contribute to the infant's day/night entrainment. There is no clear evidence that using artificial feeds improves maternal sleep. Most infants need night feeds but requirements for nighttime feeds vary with the individual.

Aim: To explore a less invasive way of assessing preload in neonates than fitting catheters to measure central venous pressure (CVP). This study evaluated the relationship between inferior vena cava (IVC) measurements and gestational age (GA) or body weight (BW) in term and premature infants and the correlation between those measurements and CVP in sick infants under mechanical ventilation., Methods: We studied 57 clinically stable infants, together with 14 sick infants fitted with central venous catheters to measure CVP. Subcostal transverse views were recorded at the level of the left branch of portal vein, and the minimum (DS ) and maximum (DL ) diameters of the IVC were measured. We evaluated the values of DS and DL and the S/L ratio (DS divided by DL ) in the clinically stable infants and the correlation between S/L and CVP in the sick infants with central catheters., Results: DS and DL correlated positively and strongly with both GA and BW, whereas S/L was almost independent of both GA and BW and correlated strongly with CVP., Conclusion: At the subcostal transverse views, S/L is much less affected by either GA or BW than DS or DL and correlates strongly with CVP in mechanically ventilated infants., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background and Objectives: Fentanyl is a synthetic opioid commonly used as an anesthetic and also increasingly popular as a sedative agent in neonates. Initial dosage regimens in this population are often empirically derived from adults on a body weight basis. However, ontogenic maturation processes related to drug disposition are not necessarily always body weight correlates. We developed a predictive pharmacokinetic/pharmacodynamic model that includes growth and maturation physiologic changes for fentanyl in neonatal care., Methods: Key pharmacokinetic variables and principles (protein binding, clearance, distribution) as related to fentanyl pharmacokinetic/pharmacodynamic behavior in adults (tricompartmental model) and to neonatal physiologic data (organ weights and blood flows, body composition, renal and hepatic function, etc.) were used to guide the building of a semi-physiologic ontogenic model. The model applies to a normal-term neonate without any other intervention. Then, extension to a pharmacokinetic/pharmacodynamic link model for fentanyl was made. The final model was evaluated by predicting the time course of plasma concentrations and the effect of a standard regimen of 10.5 μg/kg over a 1-h period followed by 1.5 μg/kg/h for 48 h., Results: Hepatic clearance was linked to ontogeny of unbound fraction and of α1-acid glycoprotein. All parameters were reduced in the neonate compared to adults but in a differing proportion due to qualitative changes in physiology that are analyzed and accounted for. Systemic clearance (CLS), volume of the central compartment (V1) and steady-state volume of distribution predicted by the model were 0.028 L/min, 1.26 L, and 22.04 L, respectively. Weight-corrected parameters generally decreased in adults compared with neonates, but differentially, e.g., CLS = 0.0093 versus 0.0088 L/min/kg, while V1 = 0.42 versus 0.18 L/kg (neonates vs. adults). Under such complexity a pharmacokinetic/pharmacodynamic model is the appropriate method for rational efficacy targeting. Fentanyl pharmacodynamics in neonates were considered to be similar to those in adults except for the equilibrium rate constant, which was also scaled on an ontogenic basis. The model adequately predicted the reported mean expected concentration-time profiles for the standard regimen., Conclusions: Integrated pharmacokinetic/pharmacodynamic modeling showed that the usually prescribed dosage regimens of fentanyl in neonates may not always provide the optimum degree of sedation. The model could be used in optimal design of clinical trials for this vulnerable population. Prospective clinical testing is the reasonable next step.

Background: Environmental conditions can easily affect the body temperature of newborns because their central nervous system, which helps maintain body temperature, has not yet fully developed. Monitoring changes in newborn body temperature can help prevent harm caused by abnormally high and low body temperatures. Taking rectal temperature readings is the most reliable way to obtain core temperature. However, because inserting a thermometer into a newborn's rectum may cause discomfort and present health risks, this temperature-taking approach is no longer used in clinical settings. The axillary temperature readings now used, including ear and back temperature, have not been empirically verified to accurately reflect core body temperature. Convenient-to-use electronic thermometers have replaced traditional mercury thermometers in the clinic. However, nearly all research done until recent years has employed mercury thermometers for temperature measurement, there is a paucity of research employing electronic thermometers., Purpose: The purpose of this study was to investigate relationships among five temperature measurement sites (including tympanic temperature, rectal temperature, axillary temperature, and back temperature) in newborns., Methods: This study used a descriptive-correlation design, employed convenience sampling, and collected data from August 2010 to February 2011 at a registered postpartum nursing home in Taipei. Thirty-three babies aged from 1 to 28 days old were recruited. MT-200 electronic thermometers were utilized to take back, axillary, and rectal temperature readings and an IRT4520 ear thermometer was used to take ear temperature readings. Collected data were analyzed using SPSS18.0 statistical software for descriptive statistics, Pearson correlation, generalized estimation equations (GEE), and intraclass correlation coefficient (ICC)., Results: We identified the least difference between right tympanic temperature and rectal temperature' a significant relationship between left tympanic temperature and rectal temperature, and axillary temperature as the most stable of the 5 body-temperature reading methods, with no outliers. There were no gender differences among the five body temperatures. Results revealed the ICC of the five temperature measurement sites to be low during both morning and evening measurements., Conclusions/implications for Practice: Current research suggests that tympanic temperature can replace rectal temperature readings. Findings may provide a reference to clinical nursing staffs and parents to measure newborn body temperature.

In humans, maternal cues guide newborns to the maternal breast, and transitional cues may be present in maternal-fetal fluids. The aim of the present study was to determine the consistent presence of sensorial cues in three maternal-fetal fluids--amniotic fluid, colostrum, and milk--and test the ability of these cues to produce appetitive responses in newborns. In the analytical study, gas chromatography-mass spectrometry (GC-MS) detected eight fatty acids consistently present in the amniotic fluid, colostrum, and milk from 12 healthy volunteers, but we do not find a mammalian pheromone, identified in another mammalian species (rabbits), in another 30 volunteers. In the behavioral study, we explored the ability of amniotic fluid or its fatty acids to produce appetitive responses in 19 human newborns <24 hr after birth. Exposure to swabs impregnated with amniotic fluid or an artificial fatty acid mixture produced a longer duration of facial reactions that suggested appetitive (sucking) movements compared with respective vehicles (i.e., propylene glycol or centrifuged amniotic fluid with a low fatty acid content verified by GC-MS). We conclude that the fatty acids contained in amniotic fluid may constitute a transitional sensorial cue that guides newborns to the maternal breast., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: Skin-to-skin contact (SSC) promotes physiological stability and interaction between parents and infants. Temporal analyses of predictability in EEG-sleep time series can elucidate functional brain maturation between SSC and non-SSC cohorts at similar post-menstrual ages (PMAs)., Methods: Sixteen EEG-sleep studies were performed on eight preterm infants who received 8 weeks of SSC, and compared with two non-SSC cohorts at term (N=126) that include a preterm group corrected to term age and a full term group. Two time series measures of predictability were used for comparisons., Results: The SSC premature neonate group had increased complexity when compared to the non-SSC premature neonate group at the same PMA. Discriminant analysis shows that SSC neonates at 40 weeks PMA are closer to the full term neonate non-SSC group than to the premature non-SSC group at the same PMA; suggesting that the KC intervention accelerates neurophysiological maturation of premature neonates., Conclusions: Based on the hypothesis that EEG-derived complexity increases with neurophysiological maturation as supported by previously published research, SSC accelerates brain maturation in healthy preterm infants as quantified by time series measures of predictability when compared to a similar non-SSC group., Significance: Times series methods that quantify predictability of EEG sleep in neonates can provide useful information about altered neural development after developmental care interventions such as SSC. Analyses of this type may be helpful in assessing other neuroprotection strategies., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

This study determined patterns of suction cycles by recording sucking pressure in full-term infants, normal pre-term infants and newborns with pathology (hypoxia at birth). Associations between these patterns and some clinical parameters were established in order to evaluate feeding capacity for the purpose of guiding specific stimulation and aiding hospital discharge in better health conditions. Seventy-five infants of both sexes were assessed after informed consent, grouped by their status at birth. Body weight and Apgar score were determined. Sucking pressure was evaluated with an ad-hoc device. Maximum and minimum pressure scores and the number of suction cycles were measured. Data were analyzed statistically at a significance level of p < 0.05. Maximum sucking pressure values varied between study groups. Full-term infants showed the highest pressure values and number of suction cycles. In pre-term infants, lower pressure values and fewer suction cycles were observed. Those with hypoxia showed great variability in both parameters. This study found a cyclical pattern of non-nutritive sucking in normal and high-risk newborns. Normal and preterm infants showed a significant direct correlation between suction cycles and Apgar scores at 5 minutes, but the infants with pathology due to hypoxia group did not show the same association. These findings are an important tool that will contribute to improving newborn maternal nutrition and optimizing the quality of life for high-risk newborns in our environment.

Background: We hypothesized that color Doppler-measured cerebral blood flow velocity (CD-CBFV) as measured in the three feeding arteries of the brain can be used as an estimator of global cerebral blood flow., Patients and Methods: CD-CBFV was determined as soon as possible after determination of phase-contrast magnetic resonance angiography-measured blood volume flow (PC-MRA BVF) by adding up angle-corrected time-averaged mean flow velocities of both internal carotid arteries and basilar artery. 30 newborns (gestational age ranging from 25 to 42 weeks; actual weight ranging from 1,050 to 5,858 g; postconceptional age ranging from 225 to 369 days) were investigated., Results: Doppler-determined CBFV ranged from 37 to 131 cm/s with a median of 69 cm/s. CD-CBFV showed a positive correlation with actual weight (r = 0.56, p < 0.01) and postconceptional age (r = 0.53, p < 0.01). CD-CBFV correlated positively with PC-MRA-measured BVF (r = 0.51, p < 0.01). Gestational age at birth, mechanical ventilation or gender did not influence this relationship. The limits of agreement, however, are wide, especially at higher CD-CBFV- and PC-MRA-measured BVF., Conclusion: CD-CBFV may be used as a non-invasive trend-monitoring tool to detect gross changes in global cerebral blood flow in the unstable and sick neonate., (Copyright © 2012 S. Karger AG, Basel.)

The important EEG changes that occur throughout childhood are a major challenge for the neurophysiologist. These reflect brain maturation, which is especially fast during the first year of life. This article describes normal EEG features and variants, characteristic patterns of development, as well as some patterns that are unusual for age, from the neonatal period to adolescence. We also describe how to adapt techniques and prepare patients in order to get interpretable records of appropriate duration, in neonates, infants, and young children., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: In both term and premature neonates, changes in the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV) reflect the degree of neonatal myocardial immaturity and the co-existence of foetal circulation as well as the presence of concurrent diseases., Aim: To evaluate the changes in values of systolic and diastolic LV and RV function using pulse tissue Doppler imaging (TDI) in 20 healthy term newborn infants from birth to the 28th day of life., Methods: Ventricular peak myocardial velocities were recorded during early diastole (Em wave), atrial contraction (Am wave), and systole (Sm wave). TDI derived atrioventricular (AV) intervals were measured as the period from atrial contraction (Am) to isovolumic contraction (IV), from Am to ventricular systole (Sm), from Sm to the following Am, and from IV to the following Am. The first measurements were taken as soon as possible after birth, the second on the third day, and the final one on the 28th day of life., Results: The diastolic myocardial velocities recorded in the RV were higher than those in the LV. Statistically significant differences were observed for time intervals in the RV: Am-IV and Am-Sm (day 1-3), p < 0.02; IV-Am (day 1-28), p < 0.005; Sm-Am (day 1-28), p < 0.01. Statistically significant differences for time intervals were also evident in the LV: Am-IV (day 1-28), p < 0.05; and for Sm-Am (day 1-28), p < 0.01. Mean isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) intervals remained stable for all measurements recorded in the RV. However, a statistically significant difference was evident for both ICT and IRT intervals in the LV between days 1 and 28 of life (p < 0.01)., Conclusions: 1. Cardiac TDI is feasible in the neonate. 2. In neonates, the diastolic and systolic function recorded in the RV was better than that in the LV. This may reflect the 'persistent' foetal status of this ventricle in the first day of life. 3. The differences observed in conduction times also reflect the haemodynamic changes which occur in the circulatory system of the neonate in the first month of life. 4. Further investigation of a larger population of neonates throughout the whole neonatal period is indicated.

Context: Inconsistent associations between maternal vitamin D status and fetal size have been published in small studies., Objective: Our objective was to examine the association between maternal 25-hydroxyvitamin D [25(OH)D] levels and measures of newborn and placental weight., Design and Setting: We measured maternal 25(OH)D in mothers from the Collaborative Perinatal Project, an observational cohort conducted in 12 U.S. medical centers from 1959 to 1965., Participants: Women delivering singleton, term, live births with 25(OH)D measured at a gestation of 26 wk or less (n = 2146)., Main Outcome Measures: Birth weight, ponderal index, placental weight, the placental to fetal weight ratio, and small for gestational age were measured. Hypotheses were formulated after data collection., Results: After confounder adjustment, mothers with 25(OH)D of 37.5 nmol/liter or greater gave birth to newborns with 46 g [95% confidence interval (CI), 9-82 g] higher birth weights and 0.13 cm (0.01-0.25 cm) larger head circumferences compared with mothers with less than 37.5 nmol/liter. Birth weight and head circumference rose with increasing 25(OH)D up to 37.5 nmol/liter and then leveled off (P < 0.05). No association was observed between 25(OH)D and ponderal index, placental weight, or the placental to fetal weight ratio. Maternal 25(OH)D of 37.5 nmol/liter or greater vs. less than 37.5 nmol/liter in the first trimester was associated with half the risk of small for gestational age (adjusted odds ratio 0.5; 95% CI 0.3-0.9), but no second-trimester association was observed., Conclusions: Maternal vitamin D status is independently associated with markers of physiological and pathological growth in term infants. Adequately powered randomized controlled trials are needed to test whether maternal vitamin D supplementation may improve fetal growth.

Background: In the rodent and human fetus, a diurnal cortisol rhythm is observed that is entrained in antiphase to the maternal rhythm. However, after birth, the adrenal circadian rhythm becomes unsynchronized with the clock time, and an adult-type, 24-h rhythm is observed only after a few months. Little is known about when and how the fetal adrenal circadian rhythm is synchronized with the day-night cycle., Methods: To investigate the function of adrenal circadian clock in the newborn infant, eight serial saliva samples were collected every 3 h over 24 h (starting at 0900 h) in 27 newborn infants., Results: Cortisol levels were higher during the period 1500 to earlier than 2100 h than during 0900 to earlier than 1500 h and 0300 to earlier than 0900 h (both P < 0.05). Salivary cortisol levels collected during 0 to <6, 6 to <12, and 12 to <18 hours after the clock time at birth (birth time) were higher than those collected during 18 to <24 hours after the birth time (P < 0.005, 0.05, and 0.05, respectively). The acrophase of salivary cortisol was linearly correlated with the birth time within the first 5 d of life (P < 0.005) but not thereafter., Conclusion: In the newborn infant, diurnal increase in cortisol was observed in the late afternoon and in correspondence with the birth time. The adrenal circadian rhythm acquired in utero may be reentrained by endocrinological events at birth. Such complex regulation of the adrenal circadian clock may inhibit a swift synchronization of the circadian clock to the day-night rhythm.

Background: Several studies have evaluated short-term neonatal outcome in infants with congenital lung lesions (CLL) but clinical course and lung function in the longer term have not yet been documented. We hypothesized that clinical course and lung function would be negatively affected by surgical resection., Objective: To evaluate respiratory symptoms and lung function longitudinally in the first year of life in infants with CLL, and to analyse differences herein between infants managed by observation only and infants whose affected lung parts were resected., Methods: We evaluated respiratory symptoms and lung function at 6 and 12 months in 30 patients with CLL. Functional residual capacity (FRC(p)) and maximal expiratory flow at functional residual capacity (V'(max)FRC) were measured with body plethysmography. SD scores were calculated for V'(max)FRC., Results: Prevalence of respiratory symptoms did not differ between the groups. Mean FRC(p) (95% CI) was 25.3 (23.3-27.3) in the group managed by observation versus 27.3 (25.1-29.6) in the group managed by surgery (p = 0.149). Mean (95% CI) SDS V'(max)FRC was -1.45 (-1.84 to -1.06) versus -1.41 (-1.90 to -0.91) (p = 0.892). Lung function did not change significantly over the 6-month period., Conclusion: Surgical resection did not seem to have negatively affected the clinical course and lung function. We recommend pulmonary follow-up of all CLL patients into adulthood to further identify any long-term effects of CLL and observation or surgery., (Copyright © 2012 S. Karger AG, Basel.)

Study Objectives: Sighs are thought to have a role in regulating breathing control. They may preceed a central apnea (sigh-CA) or a pause (sigh-P), particularly in quiet sleep. Recent techniques characterizing cardiorespiratory synchronization (CRS) provide sensitive measures of cardiorespiratory coupling, which is an important factor in breathing control. We speculated that the strength of CRS and direction of cardiorespiratory coupling (DC), would differ between sigh-P and sigh-CA; before and after a sigh; and with maturation., Design: Prospective study. CRS and DC were calculated from the respiratory signal and heart rate before and after sighs recorded during overnight polysomnography., Setting: Sleep laboratory., Participants: The data were selected from 15 subjects of a prospective cohort of 34 healthy infants at ages 2 weeks, 3 months and 6 months., Interventions: N/A., Measurements and Results: Both CRS and respiratory modulation on heart rate (RMH) (negative DC index) were decreased around sigh-CA compared with sigh-P at all ages. Short-term CRS decreased after both sigh-P and sigh-CA in infants aged 2 weeks and 3 months. Long term CRS did not change before and after sigh-P or sigh-CA. CRS and RMH were increased at 3 months and 6 months compared to 2 weeks., Conclusions: A sigh was not found to be associated with apparent resetting of breathing control in healthy infants less than 6 months of age. Cardiorespiratory coupling appears to be a leading marker of changes in breathing control, preceding central apnea associated with a sigh., Citation: Nguyen CD; Dakin C; Yuill M; Crozier S; Wilson S. The effect of sigh on cardiorespiratory synchronization in healthy sleeping infants. SLEEP 2012;35(12):1643-1650.

Autonomic nervous system modulation of heart rate is significantly altered during painful procedures in newborns. Most studies investigating pain employed only linear-based analysis methods, thus ignoring the complex, non-linear nature of heart rate control mechanisms. The emergences of dynamic, nonlinear analysis methods enable us to uncover information embedded in the fluctuations of heart rate not otherwise noticeable. Our objective was to examine how cardiac dynamics change in newborns who undergo heel lancing by analyzing linear and nonlinear characteristics of heart rate fluctuations. We used dynamic nonlinear analyses methods to reveal heart rate variability and complexity alterations during painful stimulus in newborns. Poincaré plots were applied to examine the dynamics of the system, sample entropy to investigate the complexity of the system, and detrended fluctuation analysis, to reveal the fractal properties of the system. Heart rate significantly increased (165 vs.123 beats per minute, p < 0.001) while variability decreased. Sample entropy and the quantitative measures of the Poincaré plots (SD1 and SD2) significantly decreased during heel lancing (0.75 vs. 1.0, p < 0.01; 6.4 vs. 12.8, p < 0.001; and 30.4 vs. 50.5, p < 0.01, respectively). Detrended fluctuation analysis showed a significant decrease in the short-term scaling exponent α1 (1.06 vs. 1.3, p < 0.001), and an increase in the long-term scaling exponent α2 (1.5 vs. 1.1, p < 0.001). Our results indicate altered complexity of heart rate variability during painful stimulus in newborns and disruption of the mechanisms that regularly control it. Such alterations resemble certain pathological conditions and may represent stress reaction.

Objectives: In previous work, we showed that a rigid larynx-like geometry can generate a sound by itself. However, very little is known about the exact mechanisms and control of the larynx during the first cry of life. The goal of this work was to understand how the very first cry is generated., Methods: Simultaneous high-speed imaging and sound recording on 2 excised 38-week term human fetus larynges were performed. The behaviors of the vocal folds and the false vocal folds were studied separately. The behavior of the vocal folds after resection of the supraglottic structures was also analyzed. A comparative acoustic analysis of the first cry and of the sound generated by the excised organs was performed., Results: Our data showed that the vocal folds in a larynx with the pressure conditions of the first cry do not generate sound themselves, but induce aerodynamic conditions leading to vibrations of other parts of the larynx., Conclusions: The similarities between the sound generated by an excised larynx and the first cry suggest a lack of neurologic control of the larynx during production of the first cry. A model-algorithm is proposed.

Objectives: Whether term infants in neonatal intensive care unit (NICU) have brainstem auditory abnormalities remains to be determined. This study aimed to detect any abnormality in brainstem auditory function in term neonates who are admitted to NICU., Methods: From a NICU, we recruited 55 term neonates with various perinatal problems. They were studied during the first week after birth using brainstem auditory evoked response (BAER), and the results were compared with normal term controls., Results: Wave I and III latencies and I-III interpeak interval of the evoked response in the NICU term neonates were similar to those in the controls. Wave V latency and I-V and III-V interpeak intervals tended to be increased at 21/s clicks. The increase was more obvious at higher rates 51 and 91/s. Analysis of variance revealed that at 21/s clicks only III-V interval was significantly increased (p < 0.05). At 51 and 91/s clicks, wave V latency and III-V and I-V intervals were significantly increased (p < 0.05-0.01). The rates of the abnormalities were seen more at higher than at lower click rates. The amplitudes of waves I, III, and V in the NICU neonates were all slightly reduced, but none differed significantly from the controls., Conclusions: There are some abnormalities in BAER in term neonates in NICU, suggesting functional abnormality in the auditory brainstem in NICU infants.

Objective: This study aimed to assess the pregnancy outcomes of women who reported social intake of low or very low alcohol levels during pregnancy., Methods: Obstetric and foetal outcomes were assessed in a prospective cohort of 1667 pregnant women who reported low or very low alcohol consumption during pregnancy (cases) and 1840 alcohol-abstainer women (controls)., Results: Among cases, alcohol consumption occurred during the first 4.4 (median) weeks of pregnancy, with a median ingestion of 1.0 (0.01-6.0) drinks/week, equivalent to 7.6 (0.09-47.5) g/week. Cigarette smoking was reported approximately four times more often in the exposed group than in the controls (p < 0.001). Pregnancy outcomes were similar between groups. There were 37 (2.4%) babies born with malformations in the exposed group and 41 (2.4%) in the control group (p = 0.9)., Conclusions: Low-to-very low levels of alcohol ingestion during pregnancy do not appear to be associated with adverse maternal or foetal outcomes.

Background: Defecation problems occur frequently in infants. A clearer insight into the normal defecation pattern is required to gain a better understanding of abnormal defecation., Aim: To describe the defecation pattern of healthy infants in The Netherlands., Methods: From a research population of 1175 healthy Dutch infants, 600 infants without any complaints were selected. The parents recorded details of feeding and defecation at the age of 1, 2 and 3 months using a standardised questionnaire and bowel diary., Results: In breastfed infants, average daily defecation frequency decreased significantly during the first 3 months (from 3.65 to 1.88 times per day), whereas no significant changes were observed in infants fed standard formula or mixed feeding. At every age both the average and the range of defecation frequency of breastfed infants were higher than those of infants receiving formula feeding. Breastfed infants had softer faeces than formula-fed infants and the colour more often was yellow. At the age of 3 months, 50% of stools of formula-fed infants were green coloured. There was no significant difference in quantity between the three types of feeding, but there existed a negative correlation between defecation frequency and quantity., Conclusion: This study gives insight into the defecation patterns of the largest cohort of healthy infants published so far. In the first 3 months of life, breastfed infants have more frequent, softer and more yellow-coloured stools than standard formula-fed infants. Green-coloured stools in standard formula-fed infants should be considered normal.