The Effect of Parental Weight and Genetics on the Body Mass Index of Very Low Birth Weight Infants as They Reach School Age.

Background: Prematurely born individuals are usually of low or normal weight in childhood; in adulthood, however, their probability of being overweight is twice that of persons born at full term. There is not yet any way to predict the weight development of premature babies.

Methods: A polygenic BMI score (BMI = body-mass index), calculated from the often very small individual effects of more than 2 million genetic variants, was recently described for adults.

The Survey of Neonates in Pomerania: Design, Recruitment and Follow-Up of the Second Cohort, 2013-2017.

Background: The Survey of Neonates in Pomerania (SNiP) is a birth cohort study conducted in Western Pomerania, Germany. SNiP-I recruited participants at birth between the years 2002 and 2008 (5801 inclusions). Since SNiP-I, population sociodemographic characteristics and the prevalence of early exposures, including overweight and gestational diabetes (GDM), have changed.

Infants < 90 days of age with late-onset sepsis display disturbances of the microbiome-immunity interplay.

Objective: We hypothesized that previously healthy infants < 90 days of age with late-onset sepsis (LOS) have disturbances of the gut microbiome with yet undefined specific immunological patterns.

Methods: We performed a prospective single-center convenience sample study between January 2019 and July 2021 in a case-control design. Routine diagnostics included conventional cultures (blood, cerebrospinal fluid, urine), PCRs and inflammatory markers in infants aged < 90 days with clinical LOS.

Language barriers and mental health problems of preschool children born very preterm in Germany.

Aim: We assessed whether behavioural and emotional problems of 5- to 6-year-old preschool children born very preterm (<32 weeks' gestation) are associated with an immigrant background and linguistic distance of their first language to the host country's official language, German.

Method: This is an observational longitudinal cohort study. Data are from the national multicentre German Neonatal Network cohort, including all very preterm births from 2009 onwards.

First postnatal lactate blood levels on day 1 and outcome of preterm infants with gestational age <29 weeks.

Background: Serum lactate levels are used as biomarkers for perinatal asphyxia, while their value for outcome prediction in preterm infants is uncertain. It was the aim of this observational study to determine the association of the first postnatal serum-lactate levels on day 1 of life and short-term outcome in preterm infants less than 29 gestational weeks.

Methods: We analysed data in a population-based cohort of German Neonatal Network (GNN) preterm infants with available first postnatal lactate levels enrolled at 22-28 weeks of gestational age (GA) between 1st of April 2009 and 31st December 2020.

Less Invasive Surfactant Administration for Preterm Infants - State of the Art.

Background: Less invasive surfactant administration (LISA) has become the preferred method of surfactant administration for spontaneously breathing babies on continuous positive airway pressure (CPAP).

Summary: The development of LISA followed the need to combine CPAP and surfactant replacement as mainstay treatment options for respiratory distress syndrome, thereby avoided exposure to positive pressure ventilation.

Key Messages: This review summarises the current knowns and unknowns of LISA including the physiological concept, its relevance for short-term and long-term outcomes and the challenges for practical implementation of LISA as part of a less invasive respiratory care bundle.

Bifidobacterium and Lactobacillus Probiotics and Gut Dysbiosis in Preterm Infants: The PRIMAL Randomized Clinical Trial.

Importance: The effects of probiotic interventions on colonization with resistant bacteria and early microbiome development in preterm infants remain to be clarified.

Objective: To examine the efficacy of Bifidobacterium longum subsp infantis, Bifidobacterium animalis subsp lactis (BB-12), and Lactobacillus acidophilus (La-5) probiotics to prevent colonization with multidrug-resistant organisms or highly epidemic bacteria (MDRO+) and to shape the microbiome of preterm infants toward the eubiotic state of healthy full-term infants.

Design, Setting, And Participants: The multicenter, double-blinded, placebo-controlled, group sequential, phase 3 Priming Immunity at the Beginning of Life (PRIMAL) randomized clinical trial, conducted from April 2018 to June 2020, included infants with gestational age of 28 to 32 weeks at 18 German neonatal units.

Effects of multistrain Bifidobacteria and Lactobacillus probiotics on HMO compositions after supplementation to pregnant women at threatening preterm delivery: design of the randomized clinical PROMO trial.

Background: As an indigestible component of human breast milk, Human Milk Oligosaccharides (HMOs) play an important role as a substrate for the establishing microbiome of the newborn. They have further been shown to have beneficial effects on the immune system, lung and brain development. For preterm infants HMO composition of human breast milk may be of particular relevance since the establishment of a healthy microbiome is challenged by multiple disruptive factors associated with preterm birth, such as cesarean section, hospital environment and perinatal antibiotic exposure.

Neonatal Sepsis Episodes and Retinopathy of Prematurity in Very Preterm Infants.

Importance: Retinopathy of prematurity (ROP) is a major morbidity of preterm infants causing visual impairment, including blindness, for which timely treatment is vital and prevention is key. Increasing evidence suggests that exposure to neonatal sepsis contributes to ROP development.

Objective: To investigate the association between neonatal sepsis and ROP in 2 large-scale cohorts of preterm infants born at less than 29 weeks' gestation.

Perinatal Outcomes of Immigrant Mothers and Their Infants Born Very Preterm across Germany.

Background: In Germany, more than 40% of infants are born to immigrant parents. Increased survival rates of very preterm (below 32 weeks gestation at birth; VP) infants have not resulted in equally improved life chances and quality of life. More information on perinatal variations in outcomes according to social inequalities, migration background, and language barriers is needed.

Lung Function of Preterm Children Parsed by a Polygenic Risk Score for Adult COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) in adults is a result of environmental risk factors and genetic factors. Polygenic COPD risk scores are highly predictive for lung function in adults. We hypothesized that a polygenic COPD risk score is also predictive for lung function in children who are born preterm.

Use and Impact of Pessary, Cerclage, and Progesterone for the Secondary Prevention of Preterm Birth: Data from the German Neonatal Network.

Background: To evaluate the use and effect of cervical stitch cerclage, pessary, and progesterone on pregnancy outcome in mothers of very low birth weight infants (VLBWI) born<32 weeks of gestation in the German Neonatal Network (GNN).

Methods: The GNN is a population-based cohort study enrolling VLBWI since 2009. We included 575 neonates from 424 mothers into our analysis, who were born between 2015 and 2019, after prenatal intervention with cerclage, pessary, progesterone or a combination between 20/0 to 25/0 weeks of gestation to prevent preterm birth.

A randomised controlled trial in preterm infants comparing prophylactic with selective "less invasive surfactant administration" (pro.LISA).

Background: Respiratory distress syndrome is the main cause of mortality and morbidity in preterm infants. "Less invasive surfactant administration" (LISA), which describes intratracheal surfactant administration to spontaneously breathing infants via a small diameter tube, is recommended as the first-line treatment in preterm infants with more than 30% supplemental oxygen. Prophylactic use of LISA in preterm infants with less than 30% supplemental oxygen was not tested in randomised controlled trials yet, and long-term outcome data of the procedure are scarce.

Erythrocyte transfusions are associated with retinopathy of prematurity in extremely low gestational age newborns.

Aim: Retinopathy of prematurity (ROP) is a major morbidity in preterm infants causing visual impairment including blindness. Prevention and timely treatment are critical. We investigated the potential role of red blood cell (RBC) transfusions as risk factor for ROP development.

Increased Expression of Anaphylatoxin C5a-Receptor-1 in Neutrophils and Natural Killer Cells of Preterm Infants.

Preterm infants are susceptible to infection and their defense against pathogens relies largely on innate immunity. The role of the complement system for the immunological vulnerability of preterm infants is less understood. Anaphylatoxin C5a and its receptors C5aR1 and -2 are known to be involved in sepsis pathogenesis, with C5aR1 mainly exerting pro-inflammatory effects.

Observational study on the neonatal outcome during the COVID-19 pandemic in Germany.

Aim: We aimed to determine stillbirth, preterm birth, perinatal complications, and the developmental outcome of children born preterm during the COVID-19 pandemic in Germany.

Methods: National data from the perinatal survey of preterm and term infants born in 2017-2020 between 22 March and 31 December were evaluated. Neurodevelopment of preterm infants at 2 years corrected age was tested with the Parent Report of Children's Abilities-Revised questionnaire and by clinical testing with Bayley scales, either before or during the COVID-19 pandemic.

Indomethacin Prophylaxis Is Associated with Reduced Risk of Intraventricular Hemorrhage in Extremely Preterm Infants Born in the Context of Amniotic Infection Syndrome.

Background: Amniotic infection syndrome (AIS) with perinatal inflammation may increase the susceptibility to intraventricular hemorrhage (IVH) in preterm infants. Given its anti-inflammatory and ductus arteriosus constricting capacities, we hypothesized that prophylactic administration of indomethacin reduces the incidence, severity, and consequences of IVH in the context of perinatal inflammation.

Methods: We evaluated data of infants born between 2009 and 2020 of 22 + 0-25+6 weeks of gestation from 68 German Neonatal Network centers.

Recurrent Late-Onset Sepsis in Extremely Low Birth Weight Infants Is Associated with Motor Deficits in Early School Age.

Introduction: Sepsis is regarded as a risk factor for brain injury in preterm infants. We herein hypothesize that extremely low birth weight infants (ELBWI, birth weight <1,000 g) having survived recurrent blood culture-proven late-onset sepsis (LOS) episodes are more likely to have an adverse long-term neurologic outcome.

Methods: In a large multicenter observational study of ELBWI ≤28 6/7 weeks, we evaluated the impact of recurrent LOS (blood culture-proven, after day 7 of life) on development at 5-6 years.

Sleep problems in infancy and early school age in very preterm infants.

Background: Sleep plays an important role for psychological and physical health, especially in infants at high risk for long-term neurodevelopmental impairment such as preterm infants.

Objective: Our study aimed at determining risk factors for long-term sleep impairment in very-preterm (VPT; <32 weeks of gestation) infants.

Methods: Sleep problems were analyzed in an observational study in infants of the German Neonatal Network born between January 1st 2009 and December 31st 2014.

Lactoferrin and Human Neutrophil Protein (HNP) 1-3 Levels During the Neonatal Period in Preterm Infants.

Antimicrobial polypeptides (APPs) are part of the innate immune system, but their specific role in the context of preterm birth is not yet understood. The aim of this investigation was to determine the systemic expression of APPs, i.e.

Association of Administration of Surfactant Using Less Invasive Methods With Outcomes in Extremely Preterm Infants Less Than 27 Weeks of Gestation.

Importance: The inclusion of less invasive surfactant administration (LISA) in the care of preterm infants has been found to be beneficial for respiratory outcomes. Recently, the OPTIMIST trial found higher mortality rates in the subgroup of infants born at 25 to 26 weeks' gestational age (GA) who received surfactant treatment while spontaneously breathing.

Objective: To analyze outcomes among LISA-exposed, highly vulnerable babies born at less than 27 weeks' GA within the large-scale observational cohort of the German Neonatal Network.

Multi-centre randomised trial of invasive and less invasive surfactant delivery methods showed similar spirometry results at 5-9 years of age.

Aim: We explored whether subnormal forced expiratory volume within 1 s (FEV ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube.

Methods: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104).

A Timely Administration of Antenatal Steroids Is Highly Protective Against Intraventricular Hemorrhage: An Observational Multicenter Cohort Study of Very Low Birth Weight Infants.

Aim: The aim of the study is to evaluate the influence of the timing of antenatal steroids (ANSs) on neonatal outcome of very low birth weight infants (VLBWI) born before 30 weeks of gestation in the German Neonatal Network.

Methods: The German Neonatal Network is a large population-based cohort study enrolling VLBWIs since 2009. We included 672 neonates, who were born between January 1, 2009 and December 31, 2019 in our analysis in 10 selected centers.