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. Median intervention-to-birth interval was the primary endpoint. RESULTS: 231 of 424 pregnant women had a cerclage only (54.5%), 76 women a pessary only (17.9%), and 27 were prescribed progesterone only (15.3%). The most common combination treatment (>1 intervention group) was cerclage plus progesterone (n=27), followed by cerclage plus pessary (n=13). The median intervention-to-birth interval for the whole cohort was 24 days (IQR 19.0 days). The earlier the intervention was started, the longer the intervention-to-birth interval lasted: When started at 20 weeks, the interval was 34 days in contrast to 11.5 days, when started at 25 weeks. The >1 group was born at a significantly higher median GA with 27.0 weeks (IQR 2.9 weeks) and a higher median birth weight of 980 g (IQR 394 g) accordingly. CONCLUSION: We propose that the earliest possible start of intervention leads to the most efficient pregnancy prolongation.

Similar adverse outcome rates with high or low oxygen saturation targets in an area with low background mortality.

Background: Randomized controlled trials have indicated reduced mortality rates in very preterm infants assigned to high compared to low oxygen saturation (SpO2) target levels, accompanied by higher rates of retinopathy of prematurity and bronchopulmonary dysplasia. However, the benefit-to-harm ratio may depend on the local background mortality risk. We therefore aimed to quantify the risk-benefit ratios of different SpO2 target ranges in 10 tertiary newborn intensive care units (NICUs) in East Germany. Methods: In a retrospective multicenter study, 1,399 infants born between 2008 and 2012 at a gestational age between 24 0/7 and 27 6/7 weeks and with a birthweight below 1,250 g were grouped according to the hospital's target SpO2 range [high oxygen saturation group (HOSG) above 90%], low oxygen saturation group (LOSG) below 90%] and the compliance of units with their target SpO2 range. The association between neonatal morbidities, neurodevelopmental outcomes, selected treatment strategies, and target SpO2 ranges was calculated using chi-squared and Mann Whitney U tests. Results: Nine of the ten participating NICUs met their SpO2 target ranges. Five units were considered as HOSG, and five units were considered as LOSG. Necrotizing enterocolitis and intraventricular hemorrhage grade ≥ 2 occurred significantly more frequently in the HOSG than in the LOSG (8.4% vs. 5.1%, p = 0.02; and 26.6% vs. 17.7%, p < 0.001). No significant differences in the mortality rate and the rate of retinopathy of prematurity were found. Conclusion: In our patient population, a lower SpO2 target range was not associated with increased safety risks in extremely preterm infants. We cannot be sure that our outcome differences are associated with differences in oxygen saturations due to the retrospective study design and the differences in site practices.

Predictive Value of the Münchener Funktionelle Entwicklungsdiagnostik Used to Determine Risk Factors for Motor Development in German Preterm Infants.

Early diagnosis of developmental delays is essential to providing early developmental care. The Münchener Funktionelle Entwicklungsdiagnostik (MFED) is a simple and cost-effective tool for diagnosing the development of infants and young children. Nevertheless, the MFED has not been a well-studied part of current research. This retrospective cohort study aims to detect risk factors and assess the impact of developmental care during the first twelve months of life, using the MFED. Furthermore, it determines the MFED's predictive value by comparing results with an international gold standard, the Bayley Scales of Infant Development II (BSID II). The study included 303 infants born between 2008-2013 in Rostock, Germany, with a birth weight of ≤1500 g and/or a gestational age of ≤32 weeks, who were evaluated with the MFED at twelve months of age. To ascertain the predictive value, 213 infants underwent BSID II assessment at 24 months of age. Intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and periventricular leukomalacia (PVL) were significantly associated with a higher risk of developmental delay across various domains. Post-discharge developmental care therapies did not indicate any clear beneficial effect on the infant's development. Nevertheless, some domains of MFED demonstrate predictive value, warranting increased attention for this diagnostic.

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

[This corrects the article DOI: 10.1055/a-2044-0203.].

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

[This corrects the article DOI: 10.1055/a-2044-0345.].

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

Aim This revised guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). It aims to improve the prediction, prevention, and management of preterm birth, based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 1 of this short version of the guideline presents statements and recommendations on the epidemiology, etiology, prediction, and primary and secondary prevention of preterm birth.

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

Aim The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

Potential Benefit of Probiotic E. Coli Nissle in Term Neonates.

BACKGROUND: Probiotics are often viewed as an immunity enhancing agent. The objective of this study was to investigate whether oral administration of Escherichia coli Nissle 1917 reduces the number of infections, their duration, and severity in the first 24 months after parturition in healthy neonates. SUBJECTS AND METHODS: This prospective, confirmatory, randomised, double-blind, placebo-controlled study enrolled 567 healthy neonates from four German and two Polish sites. Neonates received 10e8 viable E. coli Nissle (n=283) or placebo (n=284) daily in the first week and every second day in week 2 and 3. After 6 and 12 months, the subjects received additional instillations on ten subsequent days. The overall efficacy was assessed by the number of infections per observation period. RESULTS: Incidence rates of infection, infection duration and severity showed no statistically significant difference between groups after 24 months. Post-hoc analyses, however, revealed a short-term benefit of E. coli Nissle four weeks after treatment start which became less pronounced after eight weeks. E. coli Nissle was safe and well tolerated. CONCLUSIONS: A long-term effect after colonising the healthy neonate´s gut with E. coli Nissle to protect against infections could not be shown. Additional studies are needed to confirm a transitory, yet clinically significant role of probiotics in the first four weeks after parturition.

[Individualized Somatic Classification of Newborns Using Birth Weight Percentiles Based On Maternal Body Height and Weight (Results of a Validation Study)]. / Individuelle somatische Klassifikation von Neugeborenen auf der Grundlage von Körperhöhe und Körpergewicht der Mutter (Ergebnisse einer Validierungsstudie).

INTRODUCTION: Birth weight is influenced by maternal anthropometry. The SGA-rate of newborns of short and light mothers (<158 cm,<53 kg) and the LGA-rate of tall and heavy mothers (>177 cm,>79 kg) are overestimated. The LGA-rate of newborns of shorter mothers and the SGA-rate of taller mothers are underestimated. Individualized birth weight percentiles (IBWP) based on 18 maternal groups (6 groups of height combined with 3 groups of weight), sex and weeks of gestation have been published. The aim of this study is to validate IBWP by evaluating SGA-, AGA-, and LGA-rates using perinatal data. METHODS: The validation study compares IBWP (1995 to 2000, n=2.2 million singletons) with percentile values from two German cohorts (i: 1995 to 2000; n=2.3 million and ii: 2007 to 2011, n=3.2 million singletons) using newborns from the Lower Saxony Perinatal Survey (n=0.56 million singleton newborns, 2001 to 2009). SGA-, AGA-, and LGA-rates were calculated using R statistical analysis. RESULTS: Common percentile charts based on the total population 1995-2000 and 2007-2011 yielded SGA-rates among shorter mothers of 21.1 to 21.6% and LGA-rates of 2.0 to 3.1%. In taller mothers, SGA-rates were 3.3 to 3.5% and LGA-rates were 26.6 to 27.1%. IBWP achieved SGA-rates of 9.0% and LGA-rates of 11.4 to 11.6% in shorter mothers and SGA- and LGA-rates of 10% in taller mothers. DISCUSSION: IBWP consider the maternal size for estimation of the fetal growth potential and achieve expected SGA- and LGA-rates of 10%. Consideration of individual growth potential avoids underestimation and overestimation of SGA- and LGA-rates. It aided analyses of birth weight with IBWP simplify the assessment of the nutritional status.

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants.

The release of DNA by cells during extracellular trap (ET) formation is a defense function of neutrophils and monocytes. Neutrophil ET (NET) formation in term infants is reduced compared to adults. Objective: The aim was to quantify NET and monocyte ET (MET) release and the respective key enzymes myeloperoxidase (MPO) and neutrophil elastase (NE) in preterm infants. In this prospective explorative study, ET induction was stimulated by N-formylmethionine-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) in the cord blood of preterm infants (n = 55, 23-36 weeks) compared to term infants and adults. METs were quantified by microscopy, and NETs by microscopy and flow cytometry. We also determined the MPO levels within NETs and the intracellular concentrations of NE and MPO in neutrophils. The percentage of neutrophils releasing ET was significantly reduced for preterm infants compared to adults for all stimulants, and with a 68% further reduction for PMA compared to term infants (p = 0.0141). The NET area was not reduced except for when fMLP was administered. The amount of MPO in NET-producing cells was reduced in preterm infants compared to term infants. For preterm infants, but not term infants, the percentage of monocytes releasing ETs was significantly reduced compared to healthy adults for LTA and LPS stimulation. Conclusion: In preterm infants, ETs are measurable parts of the innate immune system, but are released in a reduced percentage of cells compared to adults.

Long-Term Outcome after Asphyxia and Therapeutic Hypothermia in Late Preterm Infants: A Pilot Study.

Therapeutic hypothermia (THT) is the recommended treatment for neuroprotection in (near) term newborns that experience perinatal asphyxia with hypoxic-ischemic encephalopathy. The benefit of THT in preterm newborns is unknown. This pilot study aims to investigate long-term outcomes of late preterm asphyctic infants with and without THT compared to term infants. The single-center, retrospective analysis examined medical charts of infants with perinatal asphyxia born between 2008 and 2015. Long-term outcome was assessed using the Bayley Scales of Infant Development 2 at the age of (corrected) 24 months. Term (n = 31) and preterm (n = 8) infants with THT showed no differences regarding their long-term outcomes of psychomotor development (Psychomotor Developmental Index 101 ± 16 vs. 105 ± 11, p = 0.570), whereas preterm infants had a better mental outcome (Mental Developmental Index 105 ± 13 vs. 93 ± 18, p = 0.048). Preterm infants with and without (n = 69) THT showed a similar mental and psychomotor development (Mental Developmental Index 105 ± 13 vs. 96 ± 20, p = 0.527; Psychomotor Developmental Index 105 ± 11 vs. 105 ± 15, p = 0.927). The study highlights the importance of studying THT in asphyctic preterm infants. However, this study shows limitations and should not be used as a basis for decision-making in the clinical context. Results of a multicenter trial of THT for preterm infants (ID No.: CN-01540535) have to be awaited.

Risk Factors of Growth Retardation and Developmental Deficits in Very Preterm Infants in a German Tertiary Neonatal Unit.

Over the last two decades, improvements in perinatology have led to increased survival rates of preterm infants. A large number of studies and meta-analyses have investigated of preterm infants and/or the influence of developmental care. However, the combined influence of the most frequent risk factors and developmental care on the long-term somatic, motor, and cognitive outcome of preterm infants remains unclear. This retrospective, single-center cohort study includes 256 children treated in a tertiary neonatal intensive care unit in Rostock, Germany, between 2008 and 2013. Follow-up examinations (somatic, psychomotor, and mental development) were performed at (corrected) 24 months using Bayley Scales of Infant Development II (BSID-II). Developmental care was carried out according to the legal framework and national guidelines (physiotherapy and/or early education). Bronchopulmonary dysplasia (BPD) and an exclusive formula feeding showed a 2.8-4.6-fold higher risk (95% Confidence Interval: Mental Developmental Index 1.73-7.58; Psychomotor Developmental Index 1.44-14.54; body length 1.20-6.41) for developmental deficits (mental and psychomotor developmental index; body length). Developmental care after discharge according to national guidelines did not prevent this. Since this is a retrospective pilot study, no recommendations can be made based on this analysis. Therefore, future research should evaluate whether standard developmental care should be extended by tailored measures depending on individual risk factors.

Individualized sex-specific birth weight percentiles for gestational age based on maternal height and weight.

OBJECTIVES: The maternal body size affects birth weight. The impact on birth weight percentiles is unknown. The objective of the study was to develop birth weight percentiles based on maternal height and weight. METHODS: This observational study analyzed 2.2 million singletons from the German Perinatal Survey. Data were stratified into 18 maternal height and weight groups. Sex-specific birth weight percentiles were calculated from 31 to 42 weeks and compared to percentiles from the complete dataset using the GAMLSS package for R statistics. RESULTS: Birth weight percentiles not considering maternal size showed 22% incidence of small for gestational age (SGA) and 2% incidence of large for gestational age (LGA) for the subgroup of newborns from petite mothers, compared to a 4% SGA and 26% LGA newborns from big mothers. The novel percentiles based on 18 groups stratified by maternal height and weight for both sexes showed significant differences between identical original percentiles. The differences were up to almost 800 g between identical percentiles for petite and big mothers. The 97th and 50th percentile from the group of petite mothers almost overlap with the 50th and 3rd percentile from the group of big mothers. CONCLUSIONS: There is a clinically significant difference in birth weight percentiles when stratified by maternal height and weight. It could be hypothesized that birth weight charts stratified by maternal anthropometry could provide higher specificity and more individual prediction of perinatal risks. The new percentiles may be used to evaluate estimated fetal as well as birth weight.

Active perinatal care of preterm infants in the German Neonatal Network.

OBJECTIVE: To determine if survival rates of preterm infants receiving active perinatal care improve over time. DESIGN: The German Neonatal Network is a cohort study of preterm infants with birth weight <1500 g. All eligible infants receiving active perinatal care are registered. We analysed data of patients discharged between 2011 and 2016. SETTING: 43 German level III neonatal intensive care units (NICUs). PATIENTS: 8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care. INTERVENTIONS: Participating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25-P75) and low (

[Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and the Management of Preterm Premature Rupture of Membranes]. / Prävention und Therapie der Frühgeburt. Leitlinie der DGGG, OEGGG und SGGG (S2k-Niveau, AWMF-Registernummer 015/025, Februar 2019) ­ Teil 2 mit Empfehlungen zur tertiären Prävention der Frühgeburt und zum Management des frühen vorzeitigen Blasensprungs.

AIMS: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups. METHODS: The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus). RECOMMENDATIONS: Part 2 of this short version of the guideline presents Statements and Recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

[Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth]. / Prävention und Therapie der Frühgeburt. Leitlinie der DGGG, OEGGG und SGGG (S2k-Niveau, AWMF-Registernummer 015/025, Februar 2019) ­ Teil 1 mit Empfehlungen zur Epidemiologie, Ätiologie, Prädiktion, primären und sekundären Prävention der Frühgeburt.

AIMS: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups. METHODS: Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus). RECOMMENDATIONS: Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

Aims This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups. Methods Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus). Recommendations Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.