[Individualized Somatic Classification of Newborns Using Birth Weight Percentiles Based On Maternal Body Height and Weight (Results of a Validation Study)]. / Individuelle somatische Klassifikation von Neugeborenen auf der Grundlage von Körperhöhe und Körpergewicht der Mutter (Ergebnisse einer Validierungsstudie).

INTRODUCTION: Birth weight is influenced by maternal anthropometry. The SGA-rate of newborns of short and light mothers (<158 cm,<53 kg) and the LGA-rate of tall and heavy mothers (>177 cm,>79 kg) are overestimated. The LGA-rate of newborns of shorter mothers and the SGA-rate of taller mothers are underestimated. Individualized birth weight percentiles (IBWP) based on 18 maternal groups (6 groups of height combined with 3 groups of weight), sex and weeks of gestation have been published. The aim of this study is to validate IBWP by evaluating SGA-, AGA-, and LGA-rates using perinatal data. METHODS: The validation study compares IBWP (1995 to 2000, n=2.2 million singletons) with percentile values from two German cohorts (i: 1995 to 2000; n=2.3 million and ii: 2007 to 2011, n=3.2 million singletons) using newborns from the Lower Saxony Perinatal Survey (n=0.56 million singleton newborns, 2001 to 2009). SGA-, AGA-, and LGA-rates were calculated using R statistical analysis. RESULTS: Common percentile charts based on the total population 1995-2000 and 2007-2011 yielded SGA-rates among shorter mothers of 21.1 to 21.6% and LGA-rates of 2.0 to 3.1%. In taller mothers, SGA-rates were 3.3 to 3.5% and LGA-rates were 26.6 to 27.1%. IBWP achieved SGA-rates of 9.0% and LGA-rates of 11.4 to 11.6% in shorter mothers and SGA- and LGA-rates of 10% in taller mothers. DISCUSSION: IBWP consider the maternal size for estimation of the fetal growth potential and achieve expected SGA- and LGA-rates of 10%. Consideration of individual growth potential avoids underestimation and overestimation of SGA- and LGA-rates. It aided analyses of birth weight with IBWP simplify the assessment of the nutritional status.

Individualized sex-specific birth weight percentiles for gestational age based on maternal height and weight.

OBJECTIVES: The maternal body size affects birth weight. The impact on birth weight percentiles is unknown. The objective of the study was to develop birth weight percentiles based on maternal height and weight. METHODS: This observational study analyzed 2.2 million singletons from the German Perinatal Survey. Data were stratified into 18 maternal height and weight groups. Sex-specific birth weight percentiles were calculated from 31 to 42 weeks and compared to percentiles from the complete dataset using the GAMLSS package for R statistics. RESULTS: Birth weight percentiles not considering maternal size showed 22% incidence of small for gestational age (SGA) and 2% incidence of large for gestational age (LGA) for the subgroup of newborns from petite mothers, compared to a 4% SGA and 26% LGA newborns from big mothers. The novel percentiles based on 18 groups stratified by maternal height and weight for both sexes showed significant differences between identical original percentiles. The differences were up to almost 800 g between identical percentiles for petite and big mothers. The 97th and 50th percentile from the group of petite mothers almost overlap with the 50th and 3rd percentile from the group of big mothers. CONCLUSIONS: There is a clinically significant difference in birth weight percentiles when stratified by maternal height and weight. It could be hypothesized that birth weight charts stratified by maternal anthropometry could provide higher specificity and more individual prediction of perinatal risks. The new percentiles may be used to evaluate estimated fetal as well as birth weight.

Effect on work of breathing of different continuous positive airway pressure devices evaluated in a premature neonatal lung model.

OBJECTIVE: A device for the application of continuous positive airway pressure to switch injected breathing gas to the outlet during expiration, known as Infant Flow, claims to reduce work of breathing and peak pressure change. So far the Infant Flow system has been investigated in lung models with tidal volumes of not <12 mL. However, premature neonates below 1000 g of weight generate a tidal volume of approximately 4 mL only. The aim of this study was to compare work of breathing and peak pressure change of the Infant Flow and another system that uses nasal prongs, Baby Flow, with conventional continuous positive airway pressure delivered by a pharyngeal tube. DESIGN: Laboratory investigation, basic research. SETTING: University research laboratory. MODEL: A piston pump simulating the spontaneous breathing of premature neonates was connected without leak to three different continuous positive airway pressure devices (pharyngeal tube, Baby Flow, and Infant Flow) and with a produced leak to the systems using nasal prongs (Baby Flow and Infant Flow). INTERVENTION: The pressures of the airway and continuous positive airway pressure systems and airway flow were recorded. Peak pressure change and work of breathing were determined for all systems and settings. Percentages of reduction of peak pressure change and work of breathing in relation to the continuous positive airway pressure delivered by pharyngeal tube were calculated. MEASUREMENTS AND MAIN RESULTS: The switching of injected breathing gas to the outlet during expiration of Infant Flow systems require a tidal volume of at least 5 mL. It was possible to decrease peak pressure change and work of breathing: Baby Flow system at a tidal volume of 4 mL (Inspiration: peak pressure change 82%, work of breathing 80%; Expiration: peak pressure change: 68%, work of breathing: 61%) and at a tidal volume of 8 mL (Inspiration: peak pressure change 75%, work of breathing 73%; Expiration: peak pressure change: 67%, work of breathing: 57%). Infant Flow system at tidal volume of 4 mL (Inspiration: peak pressure change 50%, work of breathing 55%; Expiration: peak pressure change: 46%, work of breathing: 43%) and at a tidal volume of 8 mL (Inspiration: peak pressure change 47%, work of breathing 46%; Expiration: peak pressure change: 24%, work of breathing: 23%), related to the continuous positive airway pressure delivered by pharyngeal tube without leak.Even under conditions of leak peak pressure change and work of breathing could be reduced: Baby Flow system at a tidal volume of 4 mL (Inspiration: peak pressure change 59%, work of breathing 64%; Expiration: peak pressure change: 68%, work of breathing: 59%) and at a tidal volume of 8 mL (Inspiration: peak pressure change 45%, work of breathing 43%; Expiration: peak pressure change: 54%, work of breathing: 53%). Infant Flow system at a tidal volume of 4 mL (Inspiration: peak pressure change 49%, work of breathing 53%; Expiration: peak pressure change: 44%, work of breathing: 40%) and at a tidal volume of 8 mL (Inspiration: peak pressure change 48%, work of breathing 43%; Expiration: peak pressure change: 36%, work of breathing: 40%), related to the continuous positive airway pressure delivered by pharyngeal tube without leak. CONCLUSION: Peak pressure change and work of breathing were decreased by Baby Flow and Infant Flow systems, even under conditions of leak.

Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants.

OBJECTIVES: To determine whether the tumor necrosis factor-α -308 G/A polymorphism is associated with blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. DESIGN: Genetic association studies. SETTING: Prospective, population-based, multicentered cohort of 1944 very-low-birth-weight infants born in 14 German study centers between 2003 and 2008 and 976 mothers, and a second prospective cohort of 926 very-low-birth-weight infants born in 2009 (German Neonatal Network). MEASUREMENTS AND MAIN RESULTS: In cohort I, 344 of 1944 (18.2%) very-low-birth-weight infants had at least one episode of blood culture-proven sepsis develop. The sepsis incidence stratified to genotype was 19.3% for G/G, 15.8% for G/A, 10.0% for A/A genotype (Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.32; 95% confidence interval, 1.03-1.71; G/G vs. A/A: odds ratio, 1.74; 95% confidence interval, 1.06-2.91; p = .03). There was a trend for association of tumor necrosis factor-α -308 A/G genotype with late-onset sepsis episodes (incidence: 17.2% for G/G, 12.5% for G/A, 10.0% for A/A genotype; Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.43; 95% confidence interval, 1.09-1.9; G/G vs. A/A: odds ratio, 2.05; 95% confidence interval, 1.19-3.56; p = .009). However, after adjustment for multiple testing, no significant associations were found. Furthermore, the genotype of the investigated 976 mothers had no impact on sepsis risk for their very-low-birth-weight infants. We additionally studied a second prospective cohort of 926 very-low-birth-weight infants and found no associations with sepsis risk. CONCLUSIONS: No association was found between the tumor necrosis factor-α -308 G/A polymorphism blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. A recent meta-analysis demonstrated that the tumor necrosis factor-α -308 A allele is associated with higher sepsis risk in adult cohorts. Thus, potential differences between adults and infants need to be incorporated in future study designs evaluating risk profiles for sepsis.

Hypothermia in a combined intoxication with doxepin and moclobemide in an adolescent.

OBJECTIVE: Intoxication with antidepressants, frequently encountered in pediatric emergency medicine, can often lead to life threatening situations. While hyperthermia, hypertonicity and rigidity are symptoms indicative of a serotonin syndrome triggered by an intoxication with serotonin reuptake inhibitors or monoamine oxidase inhibitors, cardiotoxicity, coma and ECG changes are typical of an intoxication with tricyclic antidepressants. CASE REPORT: Hypothermia (instead of the expected hyperthermia) is described for the first time as a persistent symptom during the course of a combined moclobemide-doxepin intoxication in an attempted suicide of a 16-year-old adolescent. DISCUSSION: The administration of serotonin reuptake inhibitors alone or in combination with other medication which increases the level of 5-hydroxytryptamine, i.e. serotonin, in the synaptic cleft mainly leads to hyperthermia. According to a recent study, however, the application of a selective 5-HT(1a) agonist to transgenic mice with a prominent overexpression of the 5-HT(1a) receptor lead to immobility and hypothermia. These findings might help to explain the hypothermia observed in the case of the intoxicated 16-year-old. CONCLUSION: Intoxication with antidepressants should not be excluded a priori in a hypothermic patient who displays other clinical signs of the said intoxication.

Extraabdominal malposition of the gallbladder.

Anomalies of the biliary system are rare. Anomalies of the gallbladder and anomalies of the bile ducts are distinguished. We observed a newborn with a gallbladder in an extraabdominal malposition, an anomaly that has not been previously described. Ultrasonography revealed a cystic structure with a ductlike connection with the interior surface of the liver and connecting blood vessels. On the bottom side of the liver, there was no orthotopic gallbladder. As the nature of this lesion could not be definitely clarified, an explorative laparotomy was performed. Histologic examination established the diagnosis of an ectopic gallbladder. Malformations of the extrahepatic bile passages are difficult to assess, as only a small percentage of such anomalies produce symptoms. Knowledge of the wide range of possible abnormalities in position, shape, and number of the gallbladder can help in cases where the diagnosis is unclear. Abnormally positioned gallbladders should be removed. The possibility of an ectopic gallbladder must be kept in mind when a suspicious cystic area is encountered in an atypical location, when the gallbladder is not seen in its normal location, or the preoperative diagnostic workup does not confirm the typical clinical symptoms of gallbladder disease.

Limitation of measurements of expiratory tidal volume and expiratory compliance under conditions of endotracheal tube leaks.

OBJECTIVE: Endotracheal tube leaks (ETTLs) occur in neonates ventilated with uncuffed tubes. Assuming that the influence of ETTLs might be neglected during expiration, only expiratory tidal volume is measured for calculation of expiratory compliance in cases of large ETTLs. However, expiratory ETTL might be substantial. Therefore, we evaluated the effect of ETTL size on expiratory tidal volume and compliance. DESIGN: Prospective laboratory study and retrospective clinical study. SETTING: University research laboratory and neonatal intensive care unit. PATIENTS: Sixty ventilated neonates (weight 640-2160 g, gestational age 25-33 wks) were investigated. INTERVENTIONS: The impact of increasing ETTLs on inspiratory and expiratory measured tidal volume (Vm), corrected tidal volume (Vc), and leak volume (Vl) was investigated in a ventilated neonatal lung model. The range of ETTLs (1% to 95%) was subdivided into five groups of 12 infants each. Furthermore, the relationships between standard ETTL size and inspiratory and expiratory ETTLs were evaluated using nonlinear regression. Standard ETTL size was defined as the difference between measured inspiratory and expiratory tidal volume (Vm) related to inspiratory Vm. MEASUREMENTS AND MAIN RESULTS: The size of a standard ETTL was 40% when expiratory ETTL reached 10% and was 12% when the inspiratory ETTL reached 10%. In infants, the differences between Vm and Vc were statistically significant during inspiration in the group beginning at a standard ETTL of 41% and during expiration in the group beginning at a standard ETTL of 69% (p < .05). Results of nonlinear regression showed that the standard ETTL was 33% (95% confidence interval, 28% to 36%) when expiratory ETTL reached 10% and was 13% (95% confidence interval, 12% to 15%) when inspiratory ETTL reached 10%. CONCLUSIONS: Expiratory Vl has a relevant impact if a certain ETTL size is reached.

Very low birth weight infants as a model to study genetic influences on neonatal weight gain.

In a cohort of 829 preterm infants (birth weight below 1500 g) we identified 13 monozygotic, 10 same-sex dizygotic, and 12 same-sex matched singleton pairs. The difference in daily weight gain within pairs was significantly lower in monozygotic twins compared with dizygotic twins or matched singleton pairs. Our data support a strong genetic influence on postnatal growth in preterm infants. Therefore, weight gain of preterm infants may be an interesting model to study polymorphic variants of genes regulating neonatal resorption, metabolism, or energy expenditure, and their influence on weight gain in preterm infants.

Congenital diaphragmatic hernia, etiology and management, a 10-year analysis of a single center.

OBJECTIVE: To analyze congenital diaphragmatic hernia (CDH) during a 10-year period at the University of Kiel, from 1995 through 2004, in order to develop a strategy to improve prenatal diagnosis, to be able to consider endoscopical treatment for selected cases and to assess the current postnatal treatment strategies. METHODS: Data were obtained from the fetal medicine ultrasound department, from the birth registry, from the postmortem registry, from the neonatal intensive care unit, from pediatric surgery and from the genetic database. Data were subselected for chromosomes, genetic syndromes, for isolated CDH and for associated anomalies, the lung to head ratio and lung volumes were assessed. Data were analyzed respectively for gestation at diagnosis, the type of CDH, the perinatal management and the postnatal outcome. RESULTS: There were 29 cases of CDH, in 10/29 (34%) the parents requested termination of pregnancy of which two had already died during pregnancy, 12/19 (63%) survived, which was defined as discharge from the neonatal intensive care unit, seven newborns 7/19 (37%) died in the hospital, 5 of these 5/7 (71%) were delivered in Kiel. A prenatal diagnosis was performed in 16/29 (55%), 1/16 (6%), 7/16 (43%) and 8/16 (50%) in the 1st, 2nd and 3rd trimester, respectively; in 10/29 (34%) diagnosis was performed postpartum, in 3/29 (10%) the diagnosis was performed at autopsy following termination of pregnancy. When the liver was in the abdomen, 9/10 (90%) of the children survived, compared to only 3/8 (43%) when the liver was located in the thorax. A lung to head ratio of 0.81 at 24 weeks resulted in death due to pulmonary hypoplasia. CONCLUSIONS: The overall survival in CDH is around 50%, antenatal endoscopical therapy may only be considered, if the diagnosis is performed in the early second trimester, and selection criteria such as the lung to head ratio, associated defects and the chromosomal status can be applied.

Calculation of intratracheal airway pressure in ventilated neonatal piglets with endotracheal tube leaks.

OBJECTIVE: In ventilated neonates, only the applied pressure of the ventilator is adjusted and monitored. When an endotracheal tube leaks, intratracheal pressure decreases depending on the size of the endotracheal tube and of the leak. Furthermore, an increase in resistance and/or compliance might delay the increase of intratracheal pressure during inspiration and its decline during expiration. Short inspiratory time can cause insufficient ventilation, because intratracheal pressure peak might not be reached. Short expiratory time may lead to air trapping, because intratracheal pressure could not return to baseline. The aim of this study was to develop a mathematical algorithm to calculate intratracheal pressure continuously during ventilation and to evaluate the accuracy of this method. DESIGN: Prospective, animal study. SETTING: University research laboratory. SUBJECTS: To verify the mathematical algorithm, eight neonatal piglets (1600-2600 g) were studied under different endotracheal tube leak conditions (45% to 98%). The median compliance and resistance were 1.06 mL/cm H2O/kg and 123 cm H2O/L/sec, respectively. INTERVENTIONS: Pressure decreases caused by the different endotracheal tubes were measured in a model while air flow was increased stepwise. Based on these results, a mathematical method was developed to calculate intratracheal pressure under leak conditions continuously in relation to the flow through the endotracheal tube as well as to calculate the values of resistance, compliance, and applied pressure of the ventilator. MEASUREMENTS AND MAIN RESULTS: The intratracheal pressure calculated was compared with the measured intratracheal pressure over time. The differences between measured and calculated intratracheal pressure related to peak applied pressure of the ventilator did not exceed 10%. The medians of absolute amounts of differences between measured and calculated intratracheal pressure were <1 cm H2O. CONCLUSIONS: The accuracy of the calculation of intratracheal pressure ensures adequate monitoring of artificial ventilation, even in the presence of endotracheal tube leaks. This might decrease the risk of barotrauma and improve the effectiveness of ventilation.

Correction of compliance and resistance altered by endotracheal tube leaks and non-linear pressure/volume-relationships.

Measurements of lung compliance (C) and resistance (R) are influenced by endotracheal tube leaks (ETTL) as well as non-linear pressure/volume relationships (P/V relationship). To keep C and R reliable, we developed an algorithm to mathematically correct inspiratory and expiratory volume (V) and flow. In this study, a ventilated lung model for non-linear P/V relationship with adjustment of an increasing ETTL was studied. In addition, the recordings (airway pressure, flow, and volume) of 21 infants (median weight: 1,220 g, range: 640-2,160 g, with a median leak size of 32%, range: 24-56%) were investigated. C and R were calculated continuously from the recordings of flow, volume, and airway pressure over time according to the changing volume. A method especially developed for the analysis of non-linear pressure-volume-relationship (APVNL) was employed. C and R affected by leaks were corrected applying the newly developed mathematical algorithm and compared with measurements without leakage. C could be corrected up to a leak of 80% and R up to 55% leak at half tidal V for the model with non-linear P/V-R. C and R without leak and after leak correction did not differ significantly in all infants where the APVNL method was applied (P > 0.05).

Correction of compliance and resistance altered by endotracheal tube leaks.

OBJECTIVE: Measurements of lung compliance and resistance are influenced by endotracheal tube leaks. To keep compliance and resistance reliable, we developed an algorithm to correct inspiratory and expiratory volume and flow mathematically. DESIGN: Prospective, clinical study. SETTING: University research laboratory and neonatal intensive care unit. MODEL: A ventilated lung model with a linear pressure-volume relationship and with adjustment of an increasing endotracheal tube leak was investigated. PATIENTS: A total of 21 ventilated premature neonates (median weight, 1220 g; range, 640-2160 g; median leak, 32%; range, 24-56%) were studied. MEASUREMENTS AND MAIN RESULTS: Compliance and resistance were calculated from the recordings of flow, volume, and airway pressure over time employing linear regression of the equation of motion to obtain compliance and resistance. Compliance and resistance altered by leaks were corrected and compared with measurements without leak. Compliance and resistance of the lung model could be corrected up to an endotracheal tube leak size of 86%. Compliance and resistance without leak and after leak correction did not differ significantly for all infants using the linear regression method (p >.05). For the correction of compliance in 15 and for the correction of resistance in 12 of the 21 infants, the coefficients of variation of ten measured breaths without leak were greater or equal to the differences of the values of compliance and resistance between conditions of no leak and corrected leak, respectively. CONCLUSION: Pulmonary compliance and resistance can be reliably corrected even in the presence of a substantial endotracheal tube leak, which makes pulmonary function tests more reliable.

Detection and correction of endotracheal-tube position in premature neonates.

Due to the short airways in premature children, an accurate position of the endotracheal tube (ETT) is crucial for adequate mechanical ventilation. Verification of ETT-position is done in chest radiographs. However, ETT-position varies substantially with head movement. When the head is flexed, the tube might appear too deeply inserted, and inadvertent extubation may occur in cases of retraction of ETT after radiography. Extension of the cervical spine will suggest an inappropriately high ETT-position, so that intended corrections can lead to main-stem intubation. Radiographic visible skeletal structures could serve as reference points to allow the detection of head declination and imperfect positioning of ETT. Ratios of anatomical landmarks were used to estimate head position. In this study, 111 radiographs of 24 preterm neonates with a gestational age of 24-29 weeks and weights of 500-1,000 g were analyzed. A mathematical algorithm for the detection and correction of ETT-positions, based on common chest radiographs, was developed. In 108 cases (97.3%), ETT-distance from the midtracheal level was less than 2 mm after use of the proposed correction.Thus, the suggested correction equation for head position enables verification of the actual ETT-position without requiring a defined placement of the head during radiography. Moreover, it can be helpful for estimating the depth of ETT-insertion in conditions when radiography is not available.