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Low Apgar scores and low umbilical arterial (UA) blood pH are considered indicators of adverse perinatal events. This study investigated trends of these perinatal health indicators in Germany. Perinatal data on 10,696,831 in-hospital live births from 2008 to 2022 were obtained from quality assurance institutes. Joinpoint regression analysis was used to quantify trends of low Apgar score and UA pH. Additional analyses stratified by mode of delivery were performed on term singletons with cephalic presentation. Robustness against unmeasured confounding was analyzed using the E-value sensitivity analysis. The overall rates of 5-min Apgar scores < 7 and UA pH < 7.10 in liveborn infants were 1.17% and 1.98%, respectively. For low Apgar scores, joinpoint analysis revealed an increase from 2008 to 2011 (annual percent change (APC) 5.19; 95% CI 3.66-9.00) followed by a slower increase from 2011 to 2019 (APC 2.56; 95% CI 2.00-3.03) and a stabilization from 2019 onwards (APC - 0.64; 95% CI - 3.60 to 0.62). The rate of UA blood pH < 7.10 increased significantly between 2011 and 2017 (APC 5.90; 95% CI 5.15-7.42). For term singletons in cephalic presentation, the risk amplification of low Apgar scores was highest after instrumental delivery (risk ratio 1.623, 95% CI 1.509-1.745), whereas those born spontaneous had the highest increase in pH < 7.10 (risk ratio 1.648, 95% CI 1.615-1.682).          Conclusion: Rates of low 5-min Apgar scores and UA pH in liveborn infants increased from 2008 to 2022 in Germany. What is Known: • Low Apgar scores at 5 min after birth and umbilical arterial blood pH are associated with adverse perinatal outcomes. • Prospective collection of Apgar scores and arterial blood pH data allows for nationwide quality assurance. What is New: • The rates of liveborn infants with 5-min Apgar scores < 7 rose from 0.97 to 1.30% and that of umbilical arterial blood pH < 7.10 from 1.55 to 2.30% between 2008-2010 and 2020-2022. • In spontaneously born term singletons in cephalic presentation, the rate of metabolic acidosis with pH < 7.10 and BE < -5 mmol/L in umbilical arterial blood roughly doubled between the periods 2008-2010 and 2020-2022., (© 2024. The Author(s).)

In orally fed preterm infants, poor weight gain may be linked to low fecal pancreatic elastase-1 (FPE-1) activity, indicative of exocrine pancreatic insufficiency. The objective of this study was the retrospective assessment of the effect of exogenous digestive enzyme replacement by gavage in preterm infants with growth failure and low FPE-1 (<200 μg/g). We analyzed weight gain relative to baseline and caloric intake during 14-day periods before and after institution of digestive enzyme replacement containing 6000 U lipase and 240 U protease kg -1 d -1 . Among 46 of 132 preterm infants < 1250g birth weight surviving to at least 14 days in whom FPE-1 was determined, 38 infants had low FPE-1 (< 200 μg/g), and 33 infants received exogenous digestive enzyme replacement. Average daily weight gain significantly increased from 14.4 [range 2.6-22.4] g kg -1 d -1 to 17.4 [8.4-29.0] g kg -1 d -1 (P = 0.001), as did weight gain per kcal, from 0.08 [0.02-0.13] g kcal -1 d -1 to 0.11 [0.05-0.18] g kcal -1 d -1 .Conclusion: In preterm infants with signs and symptoms of exocrine pancreatic insufficiency, exogenous digestive enzyme replacement is associated with improved growth. What is Known: • Very preterm infants on full enteral nutrition may display growth failure linked to transient poor exocrine pancreatic function. • Porcine pancreatic enzymes covered with an acid-resistant coating are too large to pass the internal diameter of most gavage tubes used in very preterm infants. What is New: • Administration of a liquid formulation of acid-resistant microbial digestive enzymes in preterm infants with growth failure and low fecal pancreatic elastase-1 values was associated with improved weight gain. • Response to exogenous digestive enzyme replacement was associated with the prior extent of growth failure., (© 2021. The Author(s).)

Intrauterine exposure to zidovudine-based combination antiretroviral therapy (cART) can cause severe anemia within the first weeks of life. Tenofovir disoproxil fumarate (TDF)-based regimens may have less hematologic side effects but may affect growth parameters. This study aimed to assess the safety of TDF for prevention of mother-to-child transmission (PMTCT) in HIV-exposed uninfected infants regarding early growth outcomes and hematologic side effects. Our retrospective observational cohort study included children born (n = 232) to HIV-infected mothers (n = 228) on cART. Blood counts were compared at birth, 4-6 weeks, and 3, 12 and 18 months of age. Growth parameters were measured at birth and 12 and 18 months of age. Data were analyzed according to treatment group (TDF and non-TDF cART regimes). The median hemoglobin (Hgb) was significantly lower in the non-TDF-based group at birth (15.4 g/dl vs. 16.9 g/dl; **p = 0.002) and at 4-6 weeks of age (9.9 g/dl vs. 10.4 g/dl; **p = 0.004). The mean corpuscular volume was higher in the non-TDF-based group (109 fl vs. 105 fl; ***p < 0.001) as well at 4-6 weeks (102 fl vs. 95 fl; ***p < 0.001). In the TDF-based group, a higher proportion of neutropenia (grade 2 and higher) compared to the non-TDF-group (21.4% vs. 11%; *p = 0.015) was observed at three months of age. This effect was transient. There was no difference in growth.Conclusions: TDF appears to have no major side effects in our cohort. Transient anemia was observed more commonly with non-TDF regimens. However, our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age.What is Known:• TDF is suspected to affect the growth of HIV-exposed uninfected infants.• Non-TDF-based cART regimes for prevention of mother-to-child transmission of HIV often result in transient anemia in the infant.What is New:• TDF appears to have no major side effects regarding the growth of HIV-exposed uninfected infants.• Our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age in these infants.

Unlabelled: Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P < 0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P < 0.01), but not in the control group (P = 0.570)., Conclusion: High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.

Unlabelled: Nasal high-frequency oscillation ventilation (nHFOV) is a non-invasive ventilation mode that applies an oscillatory pressure waveform to the airways using a nasal interface. nHFOV has been shown to facilitate carbon dioxide expiration, but little is known about its use in neonates. In a questionnaire-based survey, we assessed nHFOV use in neonatal intensive care units (NICUs) in Austria, Switzerland, Germany, the Netherlands, and Sweden. Questions included indications for nHFOV, equipment used, ventilator settings, and observed side effects. Of the clinical directors of 186 NICUs contacted, 172 (92 %) participated. Among those responding, 30/172 (17 %) used nHFOV, most frequently in premature infants <1500 g (27/30) for the indication nasal continuous positive airway pressure (nCPAP) failure (27/30). Binasal prongs (22/30) were the most common interfaces. The median (range) mean airway pressure when starting nHFOV was 8 (6-12) cm H2O, and the maximum mean airway pressure was 10 (7-18) cm H2O. The nHFOV frequency was 10 (6-13) Hz. Abdominal distension (11/30), upper airway obstruction due to secretions (8/30), and highly viscous secretions (7/30) were the most common nHFOV side effects., Conclusion: In a number of European NICUs, clinicians use nHFOV. The present survey identified differences in nHFOV equipment, indications, and settings. Controlled clinical trials are needed to investigate the efficacy and side effects of nHFOV in neonates.

Unlabelled: We report the course of dicygotic twins born preterm after 29 (4)/7 weeks of gestation due to congenital Parvovirus B19 infection causing fetal hydrops with severe anemia in one infant in whom intrauterine transfusion was impossible to perform and high levels of viremia in both infants. After being discharged, they were readmitted at 3 months of age with critical aplastic crisis. Therapy with intravenous immunoglobulin infusion resulted in decreasing viremia followed by stable hemoglobin levels in both infants., Conclusion: Intravenous immunoglobulin treatment of congenital pure red cell aplasia due to Parvovirus B19 infection in preterm infants seems to be effective to introduce viral remission and to normalize erythropoiesis.

Unlabelled: The objective of this study was to study the experiences of parents of preterm infants who use social networking sites and the potential of such sites for gathering information and facilitating personal exchange. An anonymous self-reporting questionnaire was administered to parents of infants below 1,500 g birth weight born between January 1, 2009 and December 31, 2010 in two tertiary neonatal intensive care units. Of the 278 families who were sent a questionnaire, 141 responded; 53.6 % of respondents claimed to be presently members of online social networking sites. However, only 10.7 and 18.6 % used the Internet to exchange information about their infants during the NICU stay and after discharge, respectively. Most (64.0 %) responding parents considered that currently available commercial Internet sites inadequately met their need to exchange information as parents of preterm infants. Overall, 79.1 % of respondents reported that they would be interested in joining a native-language online networking site providing (1) general information on prematurity, (2) explanations of abbreviations commonly used in a hospital setting, and (3) details of common medical problems and the treatment thereof, including the availability of local therapists and follow-up services. Also, parents wanted to engage in personal exchange online not only with other parents but also with medical staff., Conclusion: The support of parents of hospitalized preterm infants by neonatal nurses and doctors could be extended by developing an expert-controlled, online networking site providing reliable and updated information and facilitating personal exchange among parents.

Preterm newborn infants may suffer laryngeal injuries after multiple intubations and long-term mechanical ventilation. Former studies have focused on acute laryngeal injuries diagnosed by endoscopy, performed within the neonatal period. This retrospective case-control study aims to investigate the prevalence and clinical risk factors for voice disorders in former very low-birth-weight (< 1,500 g) infants (VLBW) at 1-year follow-up examinations. We screened former VLBW infants for presence of dysphonia at the corrected age of 1 year and compared cases with unaffected infants matched by birth weight and gestational age. Of the 843 former VLBW infants, admitted from January 1998 to May 2006, 18 subjects had persistent dysphonia. All cases had a birth weight below 1,000 g. Surgical ligation of a ductus arteriosus had been performed in ten infants. Duration of ventilation and number of intubations were not different between cases and controls, but a documented difficult intubation was a predictor of subsequent dysphonia. The rate of dysphonia at 1 year of life was 6.6% among formerly ventilated infants with birth weights <1,000 g (extremely low-birth-weight infants). Persistent dysphonia has to be added to the list of specific long-term consequences of extremely immature birth and given attention at follow-up examinations.

We report on a newborn infant with complex congenital heart disease (CHD) featuring double outlet right ventricle and hypoplastic left ventricle who had postductal oxygen saturation well above 95% and thus eluded pulse oximetry screening for CHD.

Coumarin embryopathy (CE) is a well-documented sequelae of prenatal exposure to vitamin K antagonists. We report on a female premature infant (25 weeks' gestation) born to a mother who had received phenprocoumon during pregnancy following mechanical heart valve replacement. The infant presented with impaired coagulation, intraventricular and minor parenchymal cerebral haemorrhages and midface hypoplasia typical of CE. In addition, there was hepatopathy with conjugated hyperbilirubinemia, elevated liver enzymes and repeated episodes of hypoglycemia upon attempts to discontinue glucose supplementation, all lasting for 4 months. There was corneal opacity with anterior segment dygenesis in the left eye, and persistent pupillary membrane, cataract and persistent hyperplastic primary vitreous in the right eye. While liver disease is an uncommon but serious side effect of vitamin K antagonists, this is the first report describing neonatal hepatopathy as part of CE. In anticoagulation of pregnant women with mechanical heart valves, vitamin K antagonists should be used with utmost restraint.

Unlabelled: Necrotising enterocolitis (NEC) is the predominant immaturity-associated disease of the bowel in the preterm neonate and leads to substantial mortality and long-term morbidity. Diagnostic features of NEC include, apart from the clinical presentation, laboratory and radiological parameters. Pneumatosis intestinalis (PI) on abdominal radiographs is regarded as a criterion of definitive proof for this disease entity. The objective of this presentation is to link the topographic pattern of PI to the clinical course in cases of suspected NEC. We report two cases of radiological appearance of colonic PI indicative of NEC without associated laboratory and/or macroscopic evidence of the disease, and with minor clinical symptoms only. Data from animal studies indicate that decreased blood supply to the small bowel is associated with more extensive bowel damage as compared to impaired colonic perfusion. Therefore the topographical distribution of PI might be a more specific sign as the general presence or absence of PI., Conclusion: The topographical pattern of pneumatosis intestinalis may be predictive of the clinical course of inflammatory bowel disease in preterm infants.

Unlabelled: To investigate effects of maternal drug abuse on neonatal hearing, auditory brain-stem evoked potentials were recorded in 132 consecutive newborn infants of mothers who had taken heroin or methadone during pregnancy, alongside 1016 neonates with and 483 hospitalized neonates without risk factors, as defined by the Joint Committee on Infant Hearing. In infants antenatally exposed to opiates, the rate of severe bilateral hearing impairment (> or =50 dB) did not differ from that of hospitalized neonates without risk factors (1.5% vs. 2.5%). In contrast, intra-uterine toxoplasmosis, syphilis, or cytomegalovirus infection, bilirubin serum concentrations >25 mg/dl, craniofacial anomalies, and mechanical ventilation for 5 days or more were independently associated with increased rates of severe hearing impairment by analysis of all 1631 infants studied., Conclusion: Newborns of opiate-addicted mothers are not at increased risk for early onset hearing loss.

L-Selectin, a leukocyte surface glycoprotein involved in white blood cell extravasation, is rapidly down-regulated after leukocyte activation. We prospectively determined lymphocyte L-selectin expression in freshly obtained cord blood samples of 98 neonates (gestational age 25-42 weeks). In eight infants with bacterial infection, the mean percentage of L-selectin(high) lymphocytes was 32.5% (SD 20.1%), compared to 60.1% (SD 18.7%) in the control group (P < 0.01). A percentage of L-selectin(high) lymphocytes of less than 42% had a sensitivity of 75% and a specificity of 82% in identifying infected newborns. Cord blood lymphocyte L-selectin expression was independent of gestational age, birth weight, umbilical artery pH, hematocrit, white blood cell count, absolute neutrophil count, C-reactive protein level, or maternal fever before delivery while there was a weak correlation with the newborn's immature/total ratio and platelet count. To our knowledge, this is the first report demonstrating downregulation of human lymphocyte L-selectin expression following activation of the immune system in vivo.