[Infant mortality in Germany (2008-2012)--lower in the former German Democratic Republic?]. / Säuglingssterblichkeit in Deutschland (2008-2012)--niedriger im Osten?

BACKGROUND: German infant mortality is ranked near the median of European countries. In Germany infant mortality is significantly higher in the German Federal Republic compared with the former German Democratic Republic. This is often used as reason for a call for structural requirements and minimum caseload for the care for very low birth weight infants. METHOD: Neonatal and infant mortality were calculated for the 16 German federal states with data from the German statistical federal office for the years 2008-2012. RESULTS: Considerable variations were found for the neonatal (1.34-3.61‰, total Germany 2.31‰) and the infant (2.38-5.20‰, 3.47‰) mortality. The rate of stillborn infants was 3.56‰. A lower neonatal mortality in the former German Democratic Republic (1.62‰ vs. 2.44‰, p<0.0001, Chi-squared test) could not be confirmed for preterm infants with birth weight less than 1 500 g. In the former German Democratic Republic stillbirth was significantly more frequent in preterm infants with birth weight 500-999 g (p<0.0001). Combined stillbirth and neonatal mortality showed no difference between the German Federal Republic and former German Democratic Republic (5.45‰ and 5.29‰, respectively, n.s.; infants less than 500 g birth weight were excluded). The average number of preterm infants per perinatal centre and federal state had no influence on state specific neonatal mortality. CONCLUSION: If stillborn infants were accounted for no difference was found between the German Federal Republic and the former German Democratic Republic regarding mortality. Comparing infant mortality of different countries has to account for stillborn infants. Considerable variation of neonatal mortality is persisting throughout Germany despite structural requirements and introduction of a minimum caseload since 2005. A lower infant mortality in the former German Democratic Republic and implications drawn from are not supported by the presented nationwide data from the German statistical federal office.

[Prevention of bone mineral deficiency in premature infants: review of the literature with focus on monitoring of urinary calcium and phosphate]. / Knochenmineralmangel bei Frühgeborenen: Prävention mittels Urinmonitoring von Kalzium und Phosphat.

BACKGROUND: Bone mineral deficiency of prematurity (BMDoP) is caused by the lack of simultaneous availability of calcium (Ca) and anorganic phosphate (P) during rapid skeletal growth. METHODS: Review of the literature on the prevention of BMDoP, with specific attention to the limitations of the monitoring of urinary calcium and phosphate concentrations. RESULTS: Intrauterine bone mineral accretion (BMA) can be achieved in preterm infants if urinary concentrations of Ca and P continuously show that the supplementation with these ions slightly exceeds the actual need. An individually adjusted supplementation with Ca and P appears rational because both growth velocity and enteral Ca absorption are highly variable and determine the need for enteral Ca and P administration. If, however, urinary concentrations of Ca and P are used to determine whether Ca and P supplementation is adequate, mechanisms affecting the urinary excretion of these ions other than nutrition have to be taken into account. Specifically, methylxanthines and diuretics increase the renal Ca losses, and the renal P threshold may be lowered in premature infants. A positive effect of physical activity on BMA has been shown in several studies. CONCLUSIONS: An individualized Ca and P supplementation in preterm infants aiming for supplementation in a slight excess of the actual need and guided by urinary Ca and P concentrations appears able to prevent BMDoP. Monitoring of urinary Ca and P concentrations needs to take into account non-nutritional factors affecting these concentrations. BMA may further be improved by physical activity.

Calcium and phosphor intake in preterm infants: sensitivity and specifity of 6-hour urine samples to detect deficiency.

Aim of the present study was to test whether six-hour (6 h) urine specimens predict the 24-hour (24 h) mineral homeostasis in individual infants born preterm. Urinary Calcium (Ca) and Phosphate (P) concentrations were studied in 60 stable infants; gestational age 34 (25-42) weeks. In 58 infants four 6 h urine specimens and in 2 infants all spot urine specimens obtained within 24 h were analyzed. In 39 infants born preterm coefficients of variation were 0.42 (SD 0.26) and 0.41 (SD 0.26) for Ca and P measurements in the four 6 h urine specimens obtained within 24 h, respectively, The mineral homeostasis of the infants was defined as Ca or P surplus homeostasis if the 24 h urinary concentrations were ≥1 mmol/l. The sensitivity, specificity, and PPV of a 6 h urinary specimen to predict Ca deficiency homeostasis (24 h urinary Ca <1 mmol/l) were 0.93 (0.77-0.98; 95%CI), 0.72 (0.43-0.90) and 0.90 (0.74-0.96). The sensitivity, specificity and PPV for urinary P were 0.8 (0.38-0.96), 0.97 (0.85-0.995), and 0.8 (0.38-0.96). In conclusion, in infants born preterm on regular 3 or 4 h feedings, 6 h urine sampling is sufficiently precise for prediction of Ca and P mineral deficiency homeostasis (PPV 0.92 and 0.83). However, measurements at regular intervals (twice weekly) are recommended not to miss any infant in mineral deficiency homeostasis.

[Current outcome quality in the care of preterm infants with birth weight less than 1 500 g as a basis for regionalisation of risk pregnancies]. / Aktuelle Ergebnisqualität der Versorgung von Frühgeborenen <1 500 g Geburtsgewicht als Grundlage für eine Regionalisierung der Risikogeburten.

BACKGROUND: For preterm infants an association between patient volume and mortality has been described. METHODS: Outcome variables were evaluated for 28 hospitals in Baden-Württemberg for the years 2004-2008. Hospitals with high patient volume were compared to hospitals with a lower patient volume. RESULTS: Outcomes for 1 164 infants in 2008 and for 4 775 infants in 2004-2008 were analysed. In 2008, mortality of preterm infants less than 32 weeks gestational age (GA) was 9.2% (n=402) in the 5 major hospitals compared to 6.5% (n=520) in the other hospitals (combined mortality 7.7%, n. s., chi-square test). In the years 2004-2008, mortality showed a greater variation in hospitals with a patient volume below 50 and mean mortality was 21.1% higher for infants less than 500 g BW. Hospitals with a patient volume >or= 50 had a lower mortality for infants with BW below 500 g and between 500 g and 749 g (18% and 11%, chi-square test: p<0.05 and <0.01, respectively). For preterm infants with GA below 24 weeks and between 24 and 25 weeks, patient volume and mortality were negatively correlated (p<0.01 and <0.0001, respectively). For infants with a BW >or= 750 g or a GA >or= 26 weeks patient volume had no effect on outcome. CONCLUSION: Regionalisation of preterm infants with BW less than 750 g and a GA less than 26 weeks may contribute to reduce mortality. Infants with BW >or= 750 g and a GA >or= 26 weeks may not benefit from indirect quality indicators such as patient volume.

Effect of Bifidobacterium lactis on the incidence of nosocomial infections in very-low-birth-weight infants: a randomized controlled trial.

BACKGROUND: Nosocomial infections endanger preterm infants. OBJECTIVE: The aim of the present controlled randomized trial was to investigate whether Bifidobacterium lactis reduces the incidence of nosocomial infections in infants with very low birth weight (VLBW; <1,500 g) <30 weeks of gestation. PATIENTS AND METHODS: In a randomized controlled trial, 183 VLBW infants <30 weeks of gestation were stratified according to gestational age (23-26 and 27-29 weeks) and early antibiotic therapy (days 1-3, yes or no) and randomly assigned to have their milk feedings supplemented with B. lactis (6 x 2.0 x 10(9) CFU/kg/day, 12 billion CFU/kg/day) or placebo for the first 6 weeks of life. Primary outcome was the 'incidence density' of nosocomial infections defined as periods of elevated C-reactive protein (>10 mg/l) from day 7 after initiation of milk feedings until the 42nd day of life (number of nosocomial infections/total number of patient days). The main secondary outcome was necrotizing enterocolitis (NEC; >or=stage 2). RESULTS: There were 93 infants in the B. lactis group and 90 in the placebo group. There was no significant difference between the two groups with regard to the incidence density of nosocomial infections (0.021 vs. 0.016; p = 0.9, chi(2) test). There were 2 cases of NEC in the B. lactis group and 4 in the placebo group. None of the blood cultures grew B. lactis. CONCLUSION: In the present setting, B. lactis at a dosage of 6 x 2.0 x 10(9) CFU/kg/day (12 billion CFU/kg/day) did not reduce the incidence density of nosocomial infections in VLBW infants. No adverse effect of B. lactis was observed.

[Regionalisation of preterm births in county districts? Yes we can!]. / Regionalisierung bei Frühgeburtsbestrebungen im ländlichen Raum? Yes we can!

BACKGROUND: In preterm labour prenatal transfer of the pregnant woman to perinatal centres or subspecialty hospitals is thought to improve outcome of very low birth weight infants (VLBW). Can preterm labour diagnosed early enough? MATERIAL: Records of the neonatal referral centre at the Ulm University Hospital (1974-2003) and of the regional neonatal working group (1986-2003). RESULTS: The rate of inborn VLBW infants increased from 40 to 95-100%. CONCLUSION: It was possible to diagnose preterm labour early enough for prenatal transfer. DISCUSSION: On the strength of past experience it may be assumed that the obstetrician's or institution's willingness to transfer mothers before delivery was the critical factor of the nearly complete regionalization.

[Thoracic alterations after surgical closure of the ductus arteriosus botallo in preterm infants]. / Thoraxveränderungen nach operativem Ductus-arteriosus-Botallo-Verschluss bei Frühgeborenen.

BACKGROUND: Left-sided thoracotomy for ligation of patent ductus arteriosus (PDA) dissects the musculus latissimus dorsi and notches a small part of the musculus trapezius. After ductal closure the 4 (th) and 5 (th) rib are adapted. This follow-up study investigated if mid- or long-term consequences on the thorax occur after this procedure. PATIENTS AND METHODS: Status of the thoracic scar, functionality of the shoulder and presence of scapulata alata or scoliosis was evaluated at median age of 6 years (range: 2.9-11.9) in 57 pre-term infants (30 male; gestational age 26 weeks (24-32); birth weight 805 g (450-2140)). RESULTS: Scoliosis was diagnosed in 1 patient (=1.8%) with Rubinstein-Taybi syndrome. The length of the thoracic scar (13.8 cm; 9.4-25.5) correlated with the patient's age (r=0.61; p=0.001). The scar was relocatable except for one case. The distance of the ventral end of the scar to the nipple was 2 cm or less in 22% of the female patients. None of the patients showed impaired function of the shoulder. Scapula alata was found in 16 (28%) patients. CONCLUSION: Thoracotomy for PDA ligation was not associated with an increased risk for scoliosis or disturbed function of the shoulder. One quarter of all infants developed scapula alata which meant an aesthetic issue for some parents.

Effect of oestradiol and progesterone replacement on bronchopulmonary dysplasia in extremely preterm infants.

OBJECTIVE: To study whether postnatal replacement of oestradiol and progesterone may help to prevent bronchopulmonary dysplasia (BPD). METHODS: This randomised placebo-controlled double-blind study enrolled 83 infants of <29 weeks gestational age and 1000 g birth weight requiring mechanical ventilation within 12 h after birth. Oestradiol (2.5 mg/kg/day) and progesterone (22.5 mg/kg/day) were given by continuous intravenous infusion of a standard lipid emulsion (15 ml/kg/day) in the replacement group (ESTRA-PRO). The placebo group received the same lipid emulsion without oestradiol or progesterone. A replacement period of at least 2 weeks but not >4 weeks was strived for and defined as "according to protocol". The primary outcome variable was the incidence of BPD or death. RESULTS: The median birth weight was 670 g (min-max 400-990 g) and the gestational age 25 weeks (23.1-28.1 weeks). The incidence of BPD or death was 48% in the placebo group and 44% in the ESTRA-PRO group (p = 0.38, one-sided testing, intention to treat analysis). In infants treated according to protocol, 32% (9 of 28) in the placebo group and 14% (3 of 21) in the ESTRA-PRO group developed BPD (p = 0.08). CONCLUSION: Replacement of oestradiol and progesterone was not effective for prevention of BPD or death in extremely preterm born infants. Better-powered trials are needed to evaluate this new approach.

[Fulminant pneumococcal sepsis in a 13 months old child with congenital asplenia]. / Fulminante Pneumokokkensepsis bei einem 13 Monate alten Kleinkind mit angeborener familiärer Asplenie.

Asplenia may predispose to fulminant invasive infections caused by encapsulated bacteria. We observed a 13 months old child with (so far unknown) congenital familiar asplenia, who died from pneumococcal sepsis. General vaccination of all infants with pneumococcal conjugate vaccine may prevent this disease, which is associated with a high rate of mortality in infants with asplenia.

[Triploidy: prompt diagnosis based on typical clinical signs in a live-born extremely low birth-weight infant]. / Triploidie: Rasche Diagnosestellung anhand der typischen klinisch erhobenen Stigmata eines lebend geborenen extrem kleinen Frühgeborenen.

A child with complete triploidy is rarely born alive. However, owing to the advances in perinatal medicine even extremely immature preterm infants receive full support in the delivery room and are admitted to the neonatal ICU. Consequently, the clinician may also have to consider the diagnosis of triploidy when faced with a dysmorphic extremely preterm infant. We report here the smallest described live born girl of 25 + 5 weeks of gestational age with typical clinical findings of complete triploidy phenotype II. The aim of the case report is to make the neonatologist aware of this syndrome using photographs of this case as well as discussing the literature available. Prompt clinical diagnosis confirmed by chromosome analysis helps doctors and parents with the decision whether to continue promising or to limit futile life support measures.

Short-term outcome in infants with a birthweight less than 501 grams.

AIM: To report survival and morbidity until discharge in preterm infants <501 g with life support started immediately after birth. METHODS/STUDY DESIGN: Cohort study of all preterm infants with birthweights < 501 g born in three tertiary perinatal centres between 1 January 1998 and 31 December 2001 (gestational age (GA) 25.2 [21.0-30.7] wk; birthweight 435 [290-500] g; median [range]). RESULTS: A total of 107 infants with birthweights <501 g were born. Twenty-nine were stillborn. A prenatal decision to initiate life support immediately after birth was reached in 9/37 (24%) infants <24.0 wk GA and in 39/42 (93%) infants > or =24.0 wk GA. Survival was 3/37 (8%) and 26/41 (63%) in infants <24 wk GA and > or =24.0 wk GA, respectively. Twenty-nine of the 48 infants with immediate life support (60%) survived (95% CI: 46-75%). Forty-two of these 48 (88%) infants were small for gestational age. No infant without immediate life support survived (0/30). Twenty-three (79%) survivors developed chronic lung disease (CLD) and eight (28%) received photocoagulation for retinopathy of prematurity (ROP). CONCLUSION: In this population of extremely low birthweight infants, survival was higher than in previous studies when life support was provided immediately after birth. Short-term morbidity was similar to other studies. The presented data on survival support our concept to offer immediate life support after birth in preterm infants with birthweights <501 g. The long-term outcome of these infants needs to be assessed urgently.

Ventilation strategies and outcome in randomised trials of high frequency ventilation.

OBJECTIVE: Randomised controlled trials comparing elective use of high frequency ventilation (HFV) with conventional mechanical ventilation (CMV) in preterm infants have yielded conflicting results. We hypothesised that the variability of results may be explained by differences in study design, ventilation strategies, delay in initiation of HFV, and use of permissive hypercapnia. METHODS: Randomised controlled trials comparing the elective use of HFV with any form of CMV were identified. Trials were classified according to the ventilation strategies used for HFV and CMV and oscillator device employed. For cumulative meta-analyses, trials were arranged by the following covariables: mean duration until randomisation, Paco(2) limits, publication date, and sample size. Odds ratios (OR) and 95% confidence intervals were calculated using fixed and random effects models. RESULTS: Seventeen randomised trials enrolling 3776 patients were included. Unlike previous meta-analyses, there was no significant difference in the incidence of bronchopulmonary dysplasia or death (OR 0.87, 0.75-1.00) and severe intraventricular haemorrhage grade 3-4 (1.14, 0.96-1.37). The incidence of air leaks (OR 1.23, 1.06-1.44) was significantly increased with HFV. Subgroup analyses and cumulative meta-analyses demonstrated that trial results were related to the ventilation strategies used for HFV and CMV. No influence was found for mean time to randomisation, degree of permissive hypercapnia, or sample size. CONCLUSIONS: Heterogeneity among trials of elective HFV compared to CMV in preterm infants is mainly due to differences in ventilatory strategies. Optimising CMV strategy appeared to be as effective as using HFV in improving pulmonary outcome in preterm infants.

Hydrolysis of casein accelerates gastrointestinal transit via reduction of opioid receptor agonists released from casein in rats.

BACKGROUND: Protein hydrolysate accelerates gastrointestinal transit (GIT) and feeding advancement in preterm infants compared to native protein. In rat pups, opioid receptor agonists released from casein during digestion such as beta-casomorphins slow down GIT. We hypothesized that hydrolysis of casein reduces the opioid activity released during digestion thereby accelerating GIT compared to native casein. OBJECTIVE: The aim of the present study was to investigate whether casein hydrolysate accelerates GIT compared to native casein and whether pretreatment with naloxone, an opioid receptor blocker, abolishes this difference in rat pups. METHODS: In a randomized controlled trial following a 2 x 2 factorial design, 216 female Wistar rat pups were fed with pellets based on hydrolyzed or native casein. After pretreatment with naloxone or normal saline, carmine red was administered by oro-gastric gavage as a tracer for GIT velocity measurement. Four hours later the animals were sacrificed, their intestine was removed and the length of the colon from the cecocolonic junction to the anus was measured. GIT was recorded as percentage of the total colonic length (percentage of colonic transit) passed by carmine red. Data were given as mean +/- SD. RESULTS: GIT was significantly higher with hydrolyzed casein compared to native casein formula (77.4 +/- 17 and 51.2 +/- 20%), but there was no difference after naloxone pretreatment (77.1 +/- 16 and 76.5 +/- 17%). DISCUSSION: The present data suggest that hydrolysis of casein accelerates GIT via reduction of opioid activity released during digestion. Further studies are required to investigate to which extent these rat pub data apply to preterm infants.

Reference values for urinary calcium and phosphorus to prevent osteopenia of prematurity.

The prevention of osteopenia of prematurity is an important issue in the care of preterm infants. Fetal bone mineral accretion has been achieved in preterm infants by establishing and maintaining a simultaneous slight excretion of calcium (Ca) and phosphorus (P) (urine concentrations of 1-2 mmol/l) by means of an individual supplementation with Ca and/or P, resulting in a slight surplus supply (SSS). In this issue, Aladangady et al. present associations between urinary Ca/Cr and PO(4)/Cr ratios of preterm infants and biochemical variables of bone mineral metabolism. However, to date it has not been proven that these variables are a reliable substitute for direct measurement of bone mineral content (BMC). Before Ca/Cr and PO(4)/Cr ratios can be recommended as a new reference for improving BMC, the following steps are required: (1) direct measurement of BMC, (2) a prospective interventional trial to test and compare this new reference with the existing one (SSS, urinary Ca and P of 1-2 mmol/l) investigating BMC as primary outcome, and (3) adequate proof that Ca and P/Cr ratios are superior to simple urinary Ca and P concentrations.

Transcutaneous bilirubinometry in very low birthweight infants.

AIM: To evaluate whether transcutaneous bilirubinometry (TcB) would be a reliable and efficient screening technique for hyperbilirubinaemia in very low birthweight (VLBW, < or =1500 g) infants in an intensive care unit setting. METHODS: TcB measurements (Minolta Airshield Jaundice Meter JM-102, Osaka, Japan) were obtained immediately before or within 10 min following routine blood sampling for plasma bilirubin concentration measurements in 124 VLBW infants not receiving phototherapy. The relationship between the two techniques was analysed by linear regression analysis. A plasma bilirubin > or =150 micromol/l was defined as hyperbilirubinaemia. The sensitivity and specificity of possible TcB cut-off readings to detect hyperbilirubinaemia was evaluated. RESULTS: There was a significant correlation between the measurements of both techniques (p < 0.0001, r = 0.68). In the present study, a TcB cut-off reading of 14 would have reduced the need for plasma bilirubin measurements by 26% without missing true hyperbilirubinaemia. CONCLUSION: The data suggest that TcB will improve VLBW infant care in an intensive care unit setting by reducing the need for invasive bilirubin concentration measurements.