Christoph Maas

Early feeding of fortified breast milk and in-hospital-growth in very premature infants: a retrospective cohort analysis

BackgroundFortified human milk may not meet all nutritional needs of very preterm infants. Early transition from complementary parenteral nutrition to full enteral feeds might further impair in-hospital growth. We aimed to investigate the impact of the cumulative intake of fortified human milk on early postnatal growth in a cohort of very low birth weight infants after early transition to full enteral feeds.MethodsRetrospective single-centre observational study. Data are presented as median (interquartile range).ResultsN = 206 very preterm infants were analysed (gestational age at birth 27.6 (25.6-29.6) weeks, birth weight 915 (668-1170) g). Full enteral feeds were established at postnatal day 8 (6-10) and adequate postnatal growth was achieved (difference in standard deviation score for weight from birth to discharge -0.105(-0.603 - -0.323)). Standard deviation score for weight from birth to day 28 decreased more in infants with a cumulative human milk intake >75% of all enteral feeds (-0.64(-1.08 - -0.34)) compared to those with <25% human milk intake (-0.41(-0.7 - -0.17); p = 0.017). At discharge, a trend towards poorer weight gain with higher proportions of human milk intake persisted. In contrast, we observed no significant difference for head circumference growth.ConclusionsOur current standardized fortification of human milk may not adequately support early postnatal growth.

Avoiding postnatal undernutrition of VLBW infants during neonatal intensive care: evidence and personal view in the absence of evidence

Inadequate nutrient intakes in the first postnatal weeks play a crucial role in the aetiology of postnatal growth restriction of very low birthweight (VLBW) infants. Efforts to improve early nutrition in these infants led to a significant reduction in postnatal growth failure. Initiation of enhanced parenteral nutrition immediately after birth and utilisation of the large potential of early enteral nutrition seem pivotal. Nevertheless, it remains challenging to further reduce the initial drop in weight and head circumference z-score and to improve body composition and linear growth. This review will summarise data on how near-fetal postnatal weight gain in VLBW infants can be achieved and makes suggestions for early nutrition of VLBW infants.

A Historic Cohort Study on Accelerated Advancement of Enteral Feeding Volumes in Very Premature Infants

Background: The optimal rate of enteral feeding (EF) advancement in very low birth weight infants is under debate. Objectives: To evaluate the effects of accelerated EF advancement on the time to full enteral feeds, on early postnatal growth as well as on the frequency of necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) in very premature infants. Methods: In a retrospective single-center historic cohort study, infants with a gestational age <32 weeks at birth and birth weight <1,500 g, born between January 1, 2006, and December 31, 2007 (n = 136), were compared with infants born between January 1, 2010, and December 31, 2010 (n = 88). In 2006/2007, enteral feeds were initiated on day 1 with 10–15 ml/kg/day and advanced by 15–20 ml/kg/day. In 2010, enteral feeds were initiated with 20 ml/kg/day on day 1 and advanced by 25–30 ml/kg/day. Full enteral feeds were defined as ≥140 ml/kg/day. Data are presented as median (P25–P75). Results: The time to establish full enteral feeds was shorter in 2010: 8 (7–11) days in 2006/2007 versus 6 (5–9) days in 2010. The incidences of NEC and FIP were 2.7 and 4.1% in 2006/2007 and 3.3 and 2.2% in 2010, respectively. Weight gain was not affected by the rate of EF advancement. Higher parenteral protein intake during week 1 in 2006/2007 was associated with better head circumference growth. Conclusions: The new approach was associated with a significantly shorter period to establish full enteral feeds. No difference in the incidence of FIP or NEC was observed; however, the study was underpowered to detect small but possibly important differences.

Relationship of Salivary and Plasma Cortisol Levels in Preterm Infants: Results of a Prospective Observational Study and Systematic Review of the Literature

Background and Objectives: (1) To investigate the relationship of salivary and plasma cortisol levels in preterm infants with a focus on the usability of salivary cortisol in diagnostic work-up of infants at risk of adrenal insufficiency. (2) To perform a systematic review addressing this question. Methods:Clinical study: We conducted a prospective observational single-center study in preterm infants. We analyzed plasma and saliva cortisol concentrations by enzyme immunoassay. Correlation analysis was used to determine the relation between salivary and plasma cortisol levels and the agreement of the measurement methods was analyzed according to Bland-Altman. Systematic review: A systematic literature search (PubMed and Embase) on the relationship of salivary and plasma cortisol levels in neonates was performed in November 2012. Results:Clinical study: We enrolled 58 preterm infants (median (interquartile range) gestational age at birth was 31.4 (28.1-32.7) weeks, birth weight 1,340 (974-1,745) g, respectively). Correlation analyses revealed a relationship of plasma cortisol and salivary cortisol levels. Rank correlation coefficient was 0.6. Estimating plasma cortisol levels based on measured salivary cortisol levels showed poor agreement of the two methods for determining plasma cortisol levels (direct and via salivary cortisol). Sensitivity and specificity of salivary cortisol for the detection of adrenal insufficiency were 0.66 and 0.62, respectively. Systematic review: Six studies in preterm infants and term neonates depicting the correlation of salivary and plasma cortisol were identified with a range of saliva-plasma correlation coefficients from 0.44 to 0.83. Conclusions: Substitution of plasma cortisol by salivary cortisol determination cannot be recommended in preterm infants because of unsatisfactory agreement between methods.

Initial treatment and early weight gain of children with Robin Sequence in Germany: a prospective epidemiological study

Background To investigate birth prevalence of Robin Sequence (RS), distribution of implemented treatments and factors influencing weight gain during initial hospitalisation. Methods Prospective population-based survey (August 2011–July 2013) on new hospital admissions of infants with RS in Germany. RS was defined as retrognathia/micrognathia and at least one of the following: upper airway obstruction, snoring or hypoxaemia; glossoptosis; feeding difficulties; failure to thrive; cleft palate or RS-associated syndrome. Birth prevalence was calculated using data from the National Bureau of Statistics and in-hospital weight gain evaluated by calculating differences in SD scores (SDS) for weight. Comparisons between cohorts were performed using the Wilcoxon/Kruskal–Wallis test or Fishers exact test. Results 151 patients with RS could be verified resulting in a birth prevalence of 11.3 per 100 000 live births. Orthodontic therapy (feeding plate or pre-epiglottic baton plate, PEBP) was applied most frequently (107 infants), followed by prone positioning (97 infants). Tracheotomy was rarely performed (n=7). For 115 infants, implementation of more than one intervention was reported. Infants with serious respiratory difficulties during initial hospitalisation (n=58) showed a more pronounced decrease in SDS for weight (median (IQR) −0.81 (−1.32 to −0.26) vs −0.48 (−0.86 to 0.02); p=0.008) whereas treatment with PEBP was associated with better weight gain (SDS-difference for weight −0.37 (−1.06 to 0.02) vs −0.74 (−1.09 to −0.35); p=0.022). Conclusions Non-surgical management is preferred for infants with RS in Germany. The extent of upper airway obstruction seemed to influence in-hospital weight gain, while use of the PEBP was associated with improved early weight gain.

Survey of Practices Regarding Utilization of Inhaled Steroids in 223 German Neonatal Units

Background: No survey has been published in recent years which primarily focuses on the prescription of inhaled corticosteroids in neonatal practice. Thus, the utilization rate of inhaled corticosteroids is unknown. Objectives: To elucidate the current utilization rate of inhaled corticosteroids in the prevention and therapy of bronchopulmonary dysplasia (BPD). Methods: We developed an 18-item questionnaire that was distributed in March 2009, via electronic mail, to the pediatricians-in-chief of all the 343 German pediatric hospitals with a neonatal unit (all levels of neonatal care). We sent electronic reminders after 4 and 8 weeks. Results: 223 hospitals (65%) returned the questionnaire. Of these, 102 (46%) administered inhaled corticosteroids to premature infants either as prophylaxis or treatment for BPD. Predominantly, treatment with inhaled steroids was seen as a ‘rescue therapy’ and used only if other therapeutic approaches had failed. Of the hospitals not administering inhaled steroids, the most frequently stated reason was ‘insufficient robust evidence to support benefit of therapy’ (57%). In the majority of hospitals (81%), the active substance of choice was budesonide. Conclusions: Of the responders, approximately 50% administer inhaled corticosteroids to premature infants either as a prophylaxis or treatment for BPD. Lack of beneficial evidence was the main reason for not administering inhaled steroids in about half of the units which took this approach. Future trials should address this discrepancy by aiming to establish a clear benefit-risk ratio of inhaled corticosteroids.

Effect of Increased Enteral Protein Intake on Growth in Human Milk–Fed Preterm Infants: A Randomized Clinical Trial

Importance Protein, supplied in currently available commercial fortifiers, may be inadequate to meet the requirements of very preterm infants; in addition, intraindividual and interindividual variability of human milk protein and energy content potentially contribute to unsatisfactory early postnatal growth. Objective To determine effects on growth of different levels of enteral protein supplementation in predominantly human milk–fed preterm infants. Design, Setting, and Participants This randomized clinical and partially blinded single-center trial was conducted in a neonatal tertiary referral center in Germany. Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth) were recruited from October 2012 to October 2014 and included 35% of 173 eligible infants. Median (interquartile range [IQR]) gestational age at birth was 29.9 (28.7-31.2) weeks. All analyses were conducted in an intention-to-treat population. Interventions Infants were randomly assigned to either a lower-protein (adding 1 g of bovine protein/100 mL of breast milk through a commercial human milk fortifier; n = 30) or a higher-protein group at a median (IQR) postnatal age of 7 (6-8) days. The higher-protein group (n = 30) received either standardized higher-protein supplementation (study fortifier adding 1.8 g of bovine protein/100 mL of breast milk [n = 15]) or individualized high-protein supplementation based on protein and fat content of administered breast milk (n = 15). Study interventions were continued for a median (IQR) of 41 (30-57) days and until definite discharge planning. Main Outcomes and Measures Primary outcome was weight gain (g/kg/d) from birth to the end of intervention. Results Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth), 33 girls, were recruited from October 2012 to October 2014 and included 35% of 173 eligible infants. Median (IQR) gestational age at birth was 29.9 (28.7-31.2) weeks. Demographic characteristics and hospital courses were similar in both groups, and birth weights ranged from 580 to 1495 g in the lower-protein group and 490 to 1470 g in the higher-protein group. Weight gain was similar in the lower- and higher-protein groups: mean (95% CI), 16.3 g/kg/d (15.4-17.1 g/kg/d) in the lower-protein group vs 16.0 g/kg/d (15.1-16.9 g/kg/d) in the higher-protein group) (P = .70), despite an increase in actual protein intake by 0.6 g/kg/d (0.4-0.7 g/kg/d) (P < .001). Head circumference and lower leg longitudinal growth were also similar, as was the proportion of cumulative total enteral feeding volume provided as breast milk: median (IQR) proportion of breast milk, 92% (79%-98%) in the lower-protein group vs 94% (62%-99%) in the higher-protein group (P = .89). Conclusions and Relevance An increase in protein intake by 0.6 g/kg/d to a mean intake of 4.3 g/kg/d did not further enhance growth of very preterm infants with a median birth weight of 1200 g, who achieved near-fetal growth rates. This might point to a ceiling effect for enteral protein intake with respect to its influence on growth. Trial Registration clinicaltrials.gov Identifier: NCT01773902

Late-onset volvulus without malrotation in extremely preterm infants - a case–control-study

BackgroundVolvulus without malrotation in preterm infants is a rare but potentially life-threatening event of unknown aetiology. Confusion with necrotising enterocolitis may delay surgical intervention thereby aggravating morbidity and mortality.We aimed at elucidating potential risk factors for, and characteristic clinical signs of, volvulus without malrotation in preterm infants.MethodsRetrospective, single-centre case-control study (2007-2011). For every index patient, five infants of similar gestational age, birth weight and birth year were evaluated. Additionally, all 9 cases of necrotising enterocolitis occurring during the above period were evaluated. Data are presented as median (interquartile range).ResultsFive extremely premature infants suffering from volvulus without malrotation were identified (gestational age at birth 24.4 (23.6-25.5) weeks, birth weight 480 (370-530) g). All were small for gestational age and female; three out of five died. Volvulus occurred several weeks after birth, whereas necrotising enterocolitis occurred significantly earlier. Beyond that, no striking differences in clinical or laboratory presentation of volvulus without malrotation and necrotising enterocolitis were found. Infants with volvulus had significantly more frequent manipulations with rectal tubes for flatulence, but there were no differences in the frequency of enemas, abdominal massage or defecation. In infants with volvulus, nasal high-frequency oscillation was used more frequently for respiratory support, and PEEP-level tended to be higher.ConclusionsIn extremely premature infants volvulus without malrotation represents a life-threatening event that occurs typically several weeks after birth with an acute abdomen and seems to affect predominantly girls. Infants requiring intensive non-invasive respiratory support might be at highest risk.

Epidemiological study on intestinal volvulus without malrotation in VLBW infants

Background We conducted a monthly epidemiological survey in Germany to detect the prevalence of volvulus without malrotation (VWM) in very low birthweight (VLBW) infants and to identify factors for a better distinction between this rare and life-threatening event and other acute abdominal diseases in preterm infants. Methods Throughout 2014 and 2015, every paediatric department in Germany was asked to report cases of VWM in infants with birth weights <1500 g to the Surveillance Unit for Rare Paediatric Conditions in Germany. Hospitals reporting a case were asked to return an anonymised questionnaire and discharge letter. Results Of 36 cases reported, detailed information was submitted on 29, with 26 meeting entry criteria. With 9896 and 10 140 VLBW infants born in Germany in 2014 and 2015, respectively, we estimated a prevalence of 1.52/1000 VLBW infants for 2014 and 1.08/1000 in 2015. No specific early symptom could be determined. 10% died, and 21% of infants developed short bowel syndrome. Calculated from all verified VWM arise death in 8% and a short bowel syndrome in 15%. Conclusion VWM is a rare source of acute abdomen in VLBW infants. No specific signs and symptoms potentially facilitating an early recognition of VWM could be found from this survey. Because the rates of death and short bowel syndrome are high, VWM should always be considered early in an acute abdomen in a VLBW infant.

Yes, we can - Achieve adequate early postnatal growth in preterm infants

References 1. Wanna GB, Dharamsi LM, Moss JR, Bennett ML, Thompson RC, Hyanes DS. Contemporary management of intracranial complications of otitis media. Otol Neurotol 2009; 31: 111–7. 2. Jackson BF, Porcher FK, Zapton DT, Losek JD. Cerebral sinovenous thrombosis in children: diagnosis and treatment. Pediatr Emerg Care 2011; 27: 874–80. 3. Bales CB, Sobol S, Wetmore R, Elden LM. Lateral sinus thrombosis as a complication of otitis media: 10-year experience at the Childrens Hospital of Philadelphia. Pediatrics 2009; 123: 709–13. 4. Ooi EH, Hilton M, Hunter G. Management of lateral sinus thrombosis: update and literature review. J Laryngol Otol 2003; 117: 932–9. 5. Symonds CP. Otitic hydrocephalus. Brain 1931; 54: 55–71. 6. Stief TW, Ulbricht K, Max M. Systemic thrombin in sepsis. In: Stief T, editor. Thrombin: function and pathophysiology. New York: Nova Science Publishers, 2011.