Early initiation of antibiotic therapy and short-term outcomes in preterm infants: a single-centre retrospective cohort analysis.

BACKGROUND: Sepsis is one of the most important complications in preterm infants. For this reason, many such infants receive antibiotics during their hospital stay. However, early antibiotic therapy has also been associated with adverse outcome. It is yet largely unclear if the time of onset of antibiotic therapy influences the outcome. We here investigated whether the timing of initiation of antibiotic therapy plays a role in the association between antibiotic exposure and short-term outcome. METHODS: Retrospective analysis of data from 1762 very low birthweight infants born in a German neonatal intensive care unit (NICU) between January 2004 and December 2021. RESULTS: Antibiotics were administered to 1214 of the 1762 (68.9%) infants. In 973 (55.2%) of the 1762 of infants, antibiotic therapy was initiated within the first two postnatal days. Only 548 (31.1%) infants did not have any antibiotic prescription during their stay in the NICU. Antibiotic exposure at every timepoint was associated with an increased risk of all short-term outcomes analysed in univariable analyses. In multivariable analyses, initiation of antibiotic therapy within the first two postnatal days and initiation between postnatal days 3 and 6 was independently associated with an increased risk of developing bronchopulmonary dysplasia (BPD) (OR 3.1 and 2.8), while later initiation of antibiotic therapy was not. CONCLUSION: Very early initiation of antibiotic therapy was associated with an increased risk of BPD. Due to the study design, no conclusions on causality can be drawn. If confirmed, our data suggest that an improved identification of infants at low risk of early-onset sepsis is needed to reduce antibiotic exposure.

Retrospective cohort analysis on pancreatic enzyme substitution in very low birthweight infants with postnatal growth failure.

OBJECTIVE: To evaluate the effects of pancreatic enzyme substitution (PES) in selected very low birthweight (VLBW) infants with poor postnatal growth despite intensified nutritional support. DESIGN: Retrospective historic cohort study with matched controls. SETTING: Single level III neonatal intensive care unit. PATIENTS: Infants with a gestational age at birth <32 weeks and birth weight <1500 g born between 1 January 2005 and 31 December 2014 (n=26) who received PES for restricted postnatal growth despite intensified enteral nutritional support in comparison with infants matched for birth weight, birth year, gestational and postnatal age (n=52). INTERVENTIONS: PES 15-93 mg/g fat with enteral feeds. MAIN OUTCOME MEASURES: The difference in SD score (SDS) differences for weight during the 7 days before and after onset of PES and weight gain in g/kg/d. Data are presented as median (P10-P90). RESULTS: Gestational age was 26.6 (24.4-29.9) weeks in enzyme substituted versus 26.4 (24.7-29.9) weeks in matched controls, and birth weight was 648(420-950)g versus 685(453-949)g. SDS differences for weight improved after onset of PES by 0.18(-0.12 to 0.53) in PES infants versus -0.04(-0.31 to 0.44) in controls. Weight gain increased in the PES group from 13.6 (4.2-22.9) g/kg/day in the week before to 19.0 (10.9-29.1) g/kg/day in the week after the onset of PES. There was no difference in weight gain in substituted subgroups receiving formula/pasteurised human milk versus unpasteurised human breast milk or who had pancreatic-specific elastase-1 concentrations in stool >200 µg/g versus≤200 µg/g. No adverse effects were noted. CONCLUSIONS: PES in selected VLBW infants with growth failure despite intensified enteral nutritional support was associated with a significant increase in weight gain in the first 7 days of PES.k.

Multicenter study on the effectiveness of the pre-epiglottic baton plate for airway obstruction and feeding problems in Robin sequence.

BACKGROUND: Treatment of Robin sequence is often either invasive or of unproven effectiveness. The pre-epiglottic baton plate (PEBP) is a well-studied alternative, yet is not widely applied internationally. We report on a prospective 3-center cohort study investigating this treatment. Based on an agreed protocol, parents of infants with Robin sequence referred to participating centers were offered enrollment, which involved taking a maxillary cast followed by endoscopy to fit the plate and sleep studies to monitor its effectiveness. Recordings were centrally analyzed by sleep specialists blinded to timing and center. Primary outcome was the mixed-obstructive apnea index, defined as the number of such apneas/h of sleep; secondary outcomes included the desaturation index to <80% pulse oximeter saturation and weight gain. RESULTS: Of 75 infants referred, 49 could be included; 1 center failed to perform appropriate sleep studies. Within a mean hospitalization of 3 weeks, the mixed-obstructive apnea index decreased (median; interquartile range) from 15.9 (6.3-31.5) to 2.3 (1.2-5.4); it decreased further to 0.7 (0.1-2.4) in the 32 infants who had a successful 3-month follow-up sleep study performed. The desaturation index normalized (from 0.38 (0-2.7) to 0.0 (0-0.1)). Mean standard deviation score for weight remained unchanged between admission and follow-up, while the proportion of tube-fed infants decreased from 74 to 14%. CONCLUSIONS: This prospective multi-center cohort study confirms retrospective audits on the effectiveness of PEBP treatment in improving upper airway obstruction and feeding problems, the main clinical problems of infants with Robin sequence. International collaboration is required to compare this with other treatment approaches. TRIAL REGISTRATION: Number NCT02266043 , Registered 30/09/2014; registered partially retrospectively.

Functional treatment of airway obstruction and feeding problems in infants with Robin sequence.

BACKGROUND: Robin sequence (RS), characterised by micrognathia/retrognathia and glossoptosis with or without cleft palate, presents with intermittent upper airway obstruction and feeding difficulties. Active intervention is required to reduce the risk of brain damage or sudden death. Most treatment options are poorly studied and/or invasive. Our group developed a functional approach including early feeding training and the pre-epiglottic baton plate (PEBP), an orthodontic appliance with a velar extension shifting the base of the tongue forward. PATIENTS AND METHODS: We evaluated the effect of this approach on sleep study results and early weight gain by searching our electronic patient database for infants with isolated RS, born at or referred to our department between 1 January 2003 and 31 December 2012 and treated with the PEBP. RESULTS: Of 122 patients identified, 360 overnight sleep study results, obtained at admission, prior to hospital discharge and 3 months postdischarge, were available (117 infants had complete data). These showed a decrease in the mixed-obstructive apnoea index from (median; IQR) 8.8 (2.1-19.7) to 1.8 (0.6-5.4); p<0.001 and 0.2 (0-1.3); p<0.001, respectively. Z-scores for weight improved from -0.7 (-1.39 to -0.24) upon admission to -0.5 (-0.90 to +0.02) at follow-up (p=0.02), accompanied by a decrease in the proportion of infants requiring nasogastric tube feeding from 66% to 8%. No infant required craniofacial surgery or tracheostomy. CONCLUSIONS: These longitudinal cohort data suggest that this functional approach may be an option to treat both, upper airway obstruction and feeding problems, in infants with isolated RS.

More than fetal urine: enteral uptake of amniotic fluid as a major predictor for fetal growth during late gestation.

UNLABELLED: The purpose of our study was to investigate the importance of amniotic fluid (AF) for fetal growth during late gestation using esophageal atresia (EA) patients as a model. In this retrospective cohort study, we compared the z-scores adapted for birth weights (BW z-scores) for each of 517 European newborns with congenital pre-gastric intestinal atresia, i.e., EA, to a European reference population. To account for the influence of the intestinal atresia on fetal growth per se, we compared adapted birth weights for each of 504 European newborns with post colonic intestinal atresia (anorectal malformation (ARM) with atresia of the anus) to the same European reference population. Analysis of the complete cohort showed (i) a significantly higher rate of small for gestational age newborns among EA compared to ARM newborns (p < 0.001) and (ii) significantly lower BW z-scores among EA compared to ARM newborns (p < 0.001). BW z-scores of EA newborns were significantly lower in term compared to preterm newborns with an inverse correlation with gestational age (GA) (Spearman correlation coefficient, r = -0.185, p < 0.001). CONCLUSIONS: Enteral uptake of AF seems to play a pivotal role in fetal growth during late gestation. WHAT IS KNOWN: • Peak velocity of fetal weight gain occurs at 33 weeks of gestation and continues until birth. During this period, fetal growth is mainly characterized by cellular hypertrophy. • Amniotic fluid (AF) comprises large amounts of hormones and growth regulators. What is New: • A significantly higher rate of small for gestational age and lower birth weights and z-scores are observed among newborn infants with congenital pre-gastric intestinal atresia. • These findings suggest that enteral uptake of AF is a major predictor for fetal growth during late gestation.

Safety profile comparison between extemporaneous and a licensed preparation of caffeine citrate in preterm infants with apnea of prematurity.

BACKGROUND: Given the lack of a licensed product (LP), extemporaneous caffeine citrate (ECC) has been used by many hospital pharmacies. OBJECTIVES: Since July 2011, an LP has been available in Germany. We prospectively compared the safety profile of ECC and LP in preterm infants with apnea of prematurity. METHODS: Between April 2010 and April 2013, selected side effects occurring with ECC or LP were documented in 6 German NICUs for infants ≤34 weeks' gestation using a longitudinal study design. The software developed for daily prescriptions in NICU residents requires entries if any of the following symptoms occurred during the last 24 h: tachycardia (resting heart rate >200/min), clinical or encephalographic seizures, gastric residuals, vomiting, or necrotizing enterocolitis (NEC). ECC and LP were administered at identical doses (20 mg/kg/day loading, 5-10 mg/kg/day maintenance) and in similar formulations either orally or intravenously. RESULTS: 562 infants with 14,590 treatment days on ECC and 538 infants with 12,813 treatment days on LP were evaluated. The mean gestational age was similar (29.20 weeks for ECC vs. 29.14 weeks for LP). No relevant differences were seen concerning tachycardia, gastric residuals, or vomiting, but ECC was associated with a higher risk of NEC (risk ratio: 2.68, 95% CI: 1.01-7.23, p = 0.047) and, albeit not significantly so, seizures (risk ratio: 1.91, 95% CI: 0.53-6.96, p = 0.35). CONCLUSION: This survey demonstrates a similar safety profile for both forms of caffeine citrate. The lower NEC and seizure rate seen with the LP is intriguing, but requires confirmation in a controlled study design.

Surgical management of extremely low birth weight infants with neonatal bowel perforation: a single-center experience and a review of the literature.

BACKGROUND: Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are major causes of morbidity in infants with extremely low birth weight (ELBW). OBJECTIVE: To evaluate the surgical procedures applied, and the survival and long-term outcome of ELBW infants with NEC and FIP in a single-center study. METHODS: Inborn and outborn ELBW infants (<1000 g) with NEC and FIP were analyzed retrospectively from 2002 to 2007. Data collected include surgical procedures, survival as well as complications, length of partial parenteral nutrition and hospital stay. The short-term and long-term outcomes after 2-7 years were assessed and compared with a matched control group. RESULTS: Out of 280 ELBW infants, 28 underwent surgery, 19 because of FIP and 9 for NEC. Fourteen infants in the FIP group were treated with primary laparotomy and 5 with peritoneal drainage (PD). In the NEC group, only 1 infant was treated with PD. PD was used for unstable patients and was always followed by secondary laparotomy after stabilization. Five of 28 (18%) surgically treated ELBW infants and 4 (14%) matched controls died. The following complications occurred in the surgical group: complete (n = 1) or minor wound dehiscence (n = 4), stoma prolapse (n = 5), parastomal hernia (n = 2), stoma fistula (n = 1), and wound infection (n = 2). Dependency on parenteral nutrition was significantly shorter in infants with FIP, while there were no differences in time to stoma closure and length of hospital stay between those with FIP and those with NEC. Eleven of 23 (47.8%) surviving patients with FIP or NEC showed developmental delay, compared with 9 of 24 (37.5%) in the controls. CONCLUSIONS: The management of EBLW infants with NEC and FIP remains challenging. Our treatment approach was associated with low mortality. Developmental delay seems to be caused by extreme prematurity rather than NEC- or FIP-related bowel perforation.

An oral appliance with velar extension for treatment of obstructive sleep apnea in infants with Pierre Robin sequence.

OBJECTIVE: A new oral appliance to treat obstructive sleep apnea in infants with Pierre Robin sequence has recently been shown to be superior to a sham procedure. We now investigate safety and long-term effects of this appliance on obstructive sleep apnea in infants with Pierre Robin sequence. DESIGN: Case series with repetitive follow-up examinations. SETTING: Tertiary neonatal intensive care unit at the University Children's Hospital Tuebingen, Germany. PATIENTS: Fifteen infants (11 girls and four boys; median age, 5 days) with Pierre Robin sequence and obstructive sleep apnea (i.e., mixed-obstructive-apnea index > 3). INTERVENTION: A custom-made intraoral appliance with velar extension was used continuously in situ from admission until 3 months after hospital discharge. MAIN OUTCOME MEASURE: The mixed-obstructive-apnea index was determined prior to the intervention at admission, at discharge, and 3 months later using polygraphic sleep studies. The geometric mean of the mixed-obstructive-apnea index and its 95% confidence interval were calculated. RESULTS: Compared with admission (mean, 17.2; 95% confidence interval, 11.1-26.7), there was a significant decrease in the mixed-obstructive-apnea index to discharge (mean, 3.8; 95% confidence interval, 2.2-6.6) and 3 months later (mean, 1.2; 95% confidence interval, 0.7-2.2; p value < .001). No severe adverse events occurred. CONCLUSIONS: This oral appliance was safe and appears to treat obstructive sleep apnea effectively in infants with Pierre Robin sequence.

A randomized clinical trial of a new orthodontic appliance to improve upper airway obstruction in infants with Pierre Robin sequence.

OBJECTIVE: To test the hypothesis that a new orthodontic appliance with a velar extension that shifts the tongue anteriorly would reduce upper airway obstruction in infants with Pierre Robin sequence (PRS). STUDY DESIGN: Eleven infants with PRS (median age, 3 days) and an apnea index (AI) >3 were studied. The effect of the new appliance on the AI was compared with that of a conventional appliance without a velar extension by using a crossover study design with random allocation. RESULTS: Compared with baseline (mean AI, 13.8), there was a significant decrease in the AI with the new appliance (3.9; P value <.001), but no change with the conventional appliance (14.8; P = .842). Thus, the relative change in AI was -71% (95% CI, -84--49) for the new appliance and +8% (95% CI, -52-142) for the conventional appliance, which was significantly different (P = .004). No severe adverse effects were observed. CONCLUSION: This new orthodontic appliance appears to be safe and effective in reducing upper airway obstruction in infants with PRS.