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- Pap, Gruel, and Panada: Early Approaches to Artificial Infant Feeding. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 26; 105(4):267-274.
This paper collects information on artificial infant feeding published before 1860, the year when commercial formula became available. We have extensive artifactual evidence of thousands of feeding vessels since the Bronze Age. Special museum collections can be found in London, Paris, Cologne, Fécamp, Toronto, New Mexico, and elsewhere. The literature on the use of animal milk for infant feeding begins with Soranus in the 2nd century CE. Literature evidence from the very first printed books in the 15th century proves that physicians, surgeons, midwives, and the laity were aware of the opportunities and risks of artificial infant feeding. Most 17th to 19th century books on infant care contained detailed recipes for one or several of the following infant foods: pap, a semisolid food made of flour or bread crumbs cooked in water with or without milk; gruel, a thin porridge resulting from boiling cereal in water or milk, and panada, a preparation of various cereals or bread cooked in broth. During the 18th century, the published opinion on artificial feeding evolved from health concerns to a moral ideology. This view ignored the social and economic pressures which forced many mothers to forego or shorten breast-feeding. Bottle-feeding has been common practice throughout history. © 2014 S. Karger AG, Basel.
- A Double-Blind Randomised Controlled Trial of Fish Oil-Based versus Soy-Based Lipid Preparations in the Treatment of Infants with Parenteral Nutrition-Associated Cholestasis. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 26; 105(4):290-296.
Background: Infants receiving prolonged parenteral nutrition (PN) are at risk of PN-associated cholestasis (PNAC). This can progress to hepatic failure and death if PN cannot be discontinued. Fish oil-based parenteral lipid preparation (FOLP) has been shown to be beneficial in case studies. Objectives: (1) To evaluate whether FOLP could halt or reverse the progression of PNAC compared with soy-based parenteral lipid preparation (SLP) and (2) to assess the effects of FOLP on liver function and physical growth. Methods: Design: double-blind randomised controlled trial. Setting: level III neonatal intensive care unit. Participants: infants with PNAC (plasma-conjugated bilirubin concentration ≥34 µmol/l or 2 mg/dl) expected to be PN-dependent for >2 weeks. Intervention: to receive either FOLP or SLP at 1.5 g/kg/day. Primary outcome measure: reversal of PNAC within 4 months after commencement of lipid treatment; secondary outcomes: rate of change of weekly liver function tests, infant growth parameters, blood lipid profile and episodes of late-onset sepsis. Results: A total of 9 infants were randomised to the FOLP group and 7 to the SLP group. There was no significant difference in reversal of PNAC at 4 months between groups. Rates of increase of plasma-conjugated bilirubin and alanine aminotransferase in the SLP group were significantly greater than the FOLP group (13.5 vs. 0.6 µmol/l per week and 9.1 vs. 1.1 IU/l per week, respectively, p = 0.03). Increased enteral nutrition was associated with significant improvement of PNAC in infants receiving FOLP compared with SLP (-8.5 vs. -1.6 µmol/l per 10% increase in enteral nutrition, respectively). The study was terminated prematurely. Conclusions: progression of PNAC in PN-dependent infants can be halted by replacing SLP with FOLP and reversed by increasing the proportion of enteral nutrition in infants receiving FOLP. Replacement of SLP with FOLP in PN-dependent infants who develop PNAC may be considered. © 2014 S. Karger AG, Basel.
- A Summary of the Iodine Supplementation Study Protocol (I2S2): A UK Multicentre Randomised Controlled Trial in Preterm Infants. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 27; 105(4):282-289.
This paper summarises the study protocol for the randomised controlled trial of iodine supplementation in preterm infants. Iodine is essential for the synthesis of thyroxine, and thyroxine is essential for normal brain development in utero and for the first 2-3 years of life. The recommended iodine intake in parenteral nutrition regimens is 1 μg/kg/day and commercially available parenteral solutions for infants reflect these recommendations. In the absence of other iodine sources, infants are vulnerable to negative iodine balance and insufficiency. As many preterm infants are fed parenterally for prolonged periods with solutions which have been shown to be iodine-deficient, the I2S2 Trial was designed to establish whether iodine supplementation of preterm infants benefits neurodevelopment. © 2014 S. Karger AG, Basel.
- Management of Hypotension in Preterm Infants (The HIP Trial): A Randomised Controlled Trial of Hypotension Management in Extremely Low Gestational Age Newborns. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 27; 105(4):275-281.
Background: Extremely preterm babies (delivered at <28 completed weeks of gestation) are frequently diagnosed with hypotension and treated with inotropic and pressor drugs in the immediate postnatal period. Dopamine is the most commonly used first-line drug. Babies who are treated for hypotension more frequently sustain brain injury, have long-term disability or die compared to those who are not. Despite the widespread use of drugs to treat hypotension in such infants, evidence for efficacy is lacking, and the effect of these agents on long-term outcomes is unknown. Hypothesis: In extremely preterm babies, restricting the use of dopamine when mean blood pressure (BP) values fall below a nominal threshold and using clinical criteria to determine escalation of support ('restricted' approach) will result in improved neonatal and longer-term developmental outcomes. Research Plan: In an international multi-centre randomised trial, 830 infants born at <28 weeks of gestation, and within 72 h of birth, will be allocated to 1 of 2 alternative treatment options (dopamine vs. restricted approach) to determine the better strategy for the management of BP, using a conventional threshold to commence treatment. The first co-primary outcome of survival without brain injury will be determined at 36 weeks' postmenstrual age and the second co-primary outcome (survival without neurodevelopmental disability) will be assessed at 2 years of age, corrected for prematurity. Discussion: It is essential that appropriately designed trials be performed to define the most appropriate management strategies for managing low BP in extremely preterm babies. © 2014 S. Karger AG, Basel.
- Pyloric Exclusion for Treatment of Complicated Duodenal Atresia. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 20; 105(4):263-266.
Duodenal atresia (DA) is a well-described congenital anomaly that usually responds well to surgical correction. Associated defects are common, and these confounding variables often influence outcome. The authors present a case of a newborn female with an unusual constellation of problems including DA with annular pancreas, trisomy 21, and coarctation of the aorta. She developed protracted complications postoperatively and was treated with an innovative surgical strategy. © 2014 S. Karger AG, Basel.
- Early Detection of Prenatal Cardiocirculatory Compromise in Small for Gestational Age Infants. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 20; 105(4):256-262.
Background: Impairment of gas and substrate exchange through the placenta leads to fetal hypoxia and growth restriction. Oxygenation of vital organs is maintained with preferential perfusion at the expense of less vital organs, challenging the fetal cardiovascular system. Objectives: To identify cardiovascular compromise in preterm small for gestational age (SGA) infants using the cardiac biomarker B-type natriuretic peptide (BNP), which indicates the workload of the myocardium. Methods: In this retrospective case-control study, 26 SGA infants born at less than 32 weeks of gestation from October 2009 to October 2010 were matched for gestational age and month of birth with 26 appropriate for gestational age (AGA) infants. Antenatal Doppler ultrasound was used to identify fetal hemodynamic changes by determination of the pulsatility index (PI) of the middle cerebral artery (MCA-PI), umbilical artery (UA-PI) and veins of the ductus venosus (DV-PIV). These indices were compared with BNP levels obtained within 6 h after birth. Results: Antenatal PIs of MCA, UA and DV were significantly related to elevated BNP levels after birth in SGA infants, but not in AGA infants (SGA: MCA-PI = r(2) 0.23, p < 0.05; UA-PI = r(2) 0.46, p < 0.01; DV-PIV = r(2) 0.31, p < 0.05). Furthermore, signs of perinatal (chronic) asphyxia coincided with elevated levels of BNP. SGA was related to more postnatal cardiocirculatory complications. No significant relations between postnatal cardiac ultrasound measurements, placenta size and BNP were found. Conclusion: BNP levels were elevated early after birth in SGA infants and corresponded positively with Doppler indices of circulatory compromise. This suggests an increased workload of the myocardium. © 2014 S. Karger AG, Basel.
- Impact of physician awareness on diagnosis of fetomaternal hemorrhage. [Journal Article]
- Neonatology 2014; 105(4):250-5.
Background:Fetomaternal hemorrhage (FMH) is a poorly understood condition in which the placenta allows transmission of fetal whole blood to the mother. FMH can cause fetal anemia resulting in critical illness, death or lifelong disability. Ascertainment of the incidence of FMH is limited by reliance on retrospective studies that are dependent on a diagnosis of FMH being made at the time of patient presentation.
Objective:To determine whether the diagnosis of FMH is made more frequently after an educational intervention to increase physician awareness of the condition.
Methods:This is a retrospective cohort study of all neonates born at our institution from 1988 through 2010. The medical records of all neonates diagnosed with anemia in the first 24 h of life were reviewed. The incidence of FMH as a documented etiology of anemia was compared between infants born before and after our educational intervention.
Results:Of 124,738 births during the study period, 572 neonates with neonatal anemia were identified. A total of 23 cases of FMH demonstrated by positive Kleihauer-Betke testing occurred in our cohort. The incidence of diagnosed FMH prior to our intervention was 22 per 1,000 anemic neonates compared to 182 per 1,000 afterwards (p < 0.001), while the incidence of neonatal anemia remained unchanged (p = 0.377).
Conclusions:FMH may be a significant cause of neonatal anemia. Diagnosis of FMH is highly dependent on physician awareness of the condition. Incorrect or absent diagnosis of the etiology of neonatal anemia has significant implications for our understanding of the epidemiology of FMH. © 2014 S. Karger AG, Basel.
- Neonatal Hemolytic Jaundice: Morphologic Features of Erythrocytes that will Help You Diagnose the Underlying Condition. [Journal Article]
- Neonatology 2014; 105(4):243-9.
Background:Many cases of severe neonatal hyperbilirubinemia never have the underlying cause of the jaundice clearly identified. Thus they are said to have 'idiopathic' severe neonatal jaundice. However, finding the exact cause, if it is a genetic condition, can enable informed anticipatory guidance regarding future episodes of hemolysis, anemia, or bilirubin cholelithiasis.
Objective:'Next generation' gene sequencing can often reveal the mutations responsible for severe neonatal hyperbilirubinemia, but wisely using this new technology involves selective application, employing this testing only if inexpensive technology fails to reveal the diagnosis.
Methods:In this review, we display and discuss five types of red blood cell morphological abnormalities that have helped us categorize cases of neonatal hemolytic jaundice.
Results:As an aid to applying inexpensive technology, we review morphological abnormalities of erythrocytes that are easily identified on a blood film. When found, these abnormalities can be important clues to the underlying hemolytic condition giving rise to neonatal jaundice.
Conclusions:Applying these simple and inexpensive methods can assist neonatologists in caring for neonates who have hemolytic jaundice. We predict that by using these principals the term 'idiopathic' neonatal jaundice will become less common as the underlying causes are identified. © 2014 S. Karger AG, Basel.
- Measuring Physiological Changes during the Transition to Life after Birth. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 6; 105(3):230-242.
The transition to life after birth is characterized by major physiological changes in respiratory and hemodynamic function, which are predominantly initiated by breathing at birth and clamping of the umbilical cord. Lung aeration leads to the establishment of functional residual capacity, allowing pulmonary gas exchange to commence. This triggers a significant decrease in pulmonary vascular resistance, consequently increasing pulmonary blood flow and cardiac venous return. Clamping the umbilical cord also contributes to these hemodynamic changes by altering the cardiac preload and increasing peripheral systemic vascular resistance. The resulting changes in systemic and pulmonary circulation influence blood flow through both the oval foramen and ductus arteriosus. This eventually leads to closure of these structures and the separation of the pulmonary and systemic circulations. Most of our knowledge on human neonatal transition is based on human (fetal) data from the 1970s and extrapolation from animal studies. However, there is renewed interest in performing measurements directly at birth. By using less cumbersome techniques (and probably more accurate), our previous understanding of the physiological transition at birth is challenged, as well as the causes and consequences for when this transition fails to progress. This review will provide an overview of physiological measurements of the respiratory and hemodynamic transition at birth. Also, it will give a perspective on some of the upcoming technological advances in physiological measurements of neonatal transition in infants who are unable to make the transition without support. © 2014 S. Karger AG, Basel.
- The Apolipoprotein Gene and Recovery from Brain Injury among Extremely Preterm Infants. [JOURNAL ARTICLE]
- Neonatology 2014 Feb 6; 105(3):227-229.
Background: Extremely preterm infants have an increased risk of brain injury and, consequently, are more likely to exhibit signs of motor, cognitive or behavioral impairment. Various factors, including genetic, may influence how the brain responds to an injury, ranging from no to complete recovery. The apolipoprotein E (APOE) gene codes for a protein in the brain involved in maintenance and repair of neurons. Objective: To determine whether any of the three APOE alleles are related to improved outcome. Methods: A total of 87 preterm infants with birth weights less than 1,000 g and no obvious preexisting brain abnormalities were genotyped for the APOE gene; 71 of these were assessed with the Bayley III Scales at a corrected age of 12-15 months. Brain MRI was obtained on a subgroup of 52 infants at term equivalent. Results: No significant relationship was found between the three APOE alleles and developmental outcomes or brain MRI findings. Conclusion: APOE does not appear to be related in a direct way to the developmental sequelae of white or gray matter injury in extremely preterm infants. © 2014 S. Karger AG, Basel.