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.

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.

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.

Identification of growth patterns of preterm and small-for-gestational age children from birth to 4 years - do they catch up?

Background A legitimate indication for growth hormone (GH) therapy in children born too light or short at birth [small-for-gestational age (SGA)] exists in Germany and the European Union only if special criteria are met. Methods We conducted a longitudinal, multi-centered study on full-term appropriate-for-gestational age (AGA, n=1496) and pre-term born SGA (n=173) and full-term SGA children (n=891) in Germany from 2006 to 2010. We analyzed height, weight, body mass index (BMI) and head circumference. Results Pre-term or full-term born SGA children were shorter, lighter and had a lower BMI from birth until 3 years of age than full-term AGA children. The growth velocity of the analyzed anthropometric measurements was significantly higher in pre-term and full-term SGA children exclusively in the first 2 years of life than in AGA children. The criteria for GH treatment were fulfilled by 12.1% of pre-term SGA children compared to only 1.3% of full-term SGA children. Conclusion For children that do not catch up growth within the first 2 years of life, an earlier start of GH treatment should be considered, because a catch-up growth later than 2 years of life does not exist. Pre-term SGA-born children more frequently fulfill the criteria for GH treatment than full-term SGA children.

[Influence of Parental Body Measurements on Birth Weight of Eutrophic Term Newborns with Special Consideration of Paternal Body Measurements]. / Zum Einfluss von Körpermaßen der Eltern auf das Geburtsgewicht von eutrophen Termingeborenen (TG) unter besonderer Berücksichtigung der Körperhöhe und des Körpergewichts des Vaters.

A significant influence of maternal body height and weight on neonatal birth outcome has been confirmed before, whereas the influence of paternal traits is rather unknown. In order to analyze the correlation between parental body measurements and the birth weight of newborns, data of 1312 eutrophic term newborns and their parents were collected based on a multicenter study in 10 participating German maternity clinics. The collected data included the birth weight of the infants and the body height and weight of their parents. The results show a significant correlation between infant birth weight and maternal body height. Even with a constant body height and body weight of fathers in a range between 176-184 cm and 76-84 kg, taller mothers gave birth to children with a higher birth weight than shorter mothers. Furthermore, higher maternal body weight is also correlated with increased birth weights, although this correlation is attenuated in higher maternal weight groups. Data regarding body weight and body height of fathers showed similar results with regard to birth weight of the newborns. At a constant maternal body height (164-172 cm) and weight (56-64 kg), the body weight of newborns significantly correlates with the body height of fathers but not with their body weight. The multivariable regression analysis resulted in the following ranking of influence factors on the birth weight of newborns: 1) body height of mother, 2) body weight of mother, 3) body height of father. The results gave support to the assumption of a certain genetic influence of parental body stature on their neonates but argue for an even stronger impact of maternal environmental conditions on the developmental status of neonates.

[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 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.

Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial.

OBJECTIVE: A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. METHODS: In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. RESULTS: A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (-3.5 g/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. CONCLUSIONS: All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.

Birth risks according to maternal height and weight - an analysis of the German Perinatal Survey.

Objective To investigate the variability in the prevalences of selected birth risks in women of different heights and weights. Methods Data from the German Perinatal Survey of 1998-2000 were analyzed: 503,468 cases contributed to our analysis of the prevalences of selected birth risks specified according to maternal weight groups, 502,562 cases contributed to our analysis according to maternal height groups and 43,928 cases contributed to our analysis of birth risks in women with a body mass index (BMI) of 21-23 kg/m2 but different heights and weights. Data analysis was performed using SPSS version 22. Results Some birth risks varied substantially by maternal height in women with a "normal" BMI of 21-23 kg/m2: the prevalence of post-term birth increased from 8.7% in women with a height of 150 cm to 13.5% in 185 cm tall women, the prevalence of preterm birth decreased from 5.9% (150 cm tall women) to 3.1% (185 cm tall women), a pathologic cardiotocography (CTG) or poor fetal heart sounds on auscultation occurred in 19.4% of the 150 cm tall women but only in 9.2% of 185 cm tall women and cephalopelvic disproportion decreased from 12.3% (150 cm tall women) to 1.2% (185 cm tall women). Analyses of women in different body height and weight groups (without restriction of BMI) likewise showed differences in the prevalences of some birth risks. Conclusion Birth risks may vary by height and weight in women with the same, "normal" BMI. BMI should not be the only way by which the impact of maternal height and weight is assessed with regard to perinatal outcomes such as birth risks.

Somatic development at birth as influenced by maternal characteristics - an analysis of the German Perinatal Survey.

We investigated the effects of maternal age, body weight, body height, weight gain during pregnancy, smoking during pregnancy, previous live births and being a single mother on somatic development at birth. We analysed data from the German Perinatal Survey for the years 1998-2000 from eight German federal states. We had available data on 508,926 singleton pregnancies and neonates in total; for 508,893 of which we could classify the neonates as small, appropriate or large for gestational age (SGA, AGA or LGA) based on the 10th and 90th birth weight percentiles. Multivariable regression analyses found statistically significant effects of a clinically relevant magnitude for smoking during pregnancy [odds ratio (OR) 2.9 for SGA births for women smoking >10 cigarettes per day], maternal height (OR 1.4 for SGA births for women <162 cm; OR 1.4 for LGA births for women >172 cm), maternal weight (OR 1.5 for SGA births for women <59 kg; OR 1.9 for LGA births for women >69 kg), weight gain during pregnancy (OR 1.9 for SGA births for women with a weight gain <8 kg; OR 2.0 for LGA births for women with a weight gain >18 kg) and previous live births (OR 2.1 for LGA births for women with one or more previous live births). Maternal age and being a single mother also had significant effects but their magnitude was small. Our analysis confirms the clinically relevant effects of smoking, maternal anthropometric measures and weight gain during pregnancy on neonatal somatic development.

Maternal body height is a stronger predictor of birth weight than ethnicity: analysis of birth weight percentile charts.

Background Anthropometric parameters such as birth weight (BW) and adult body height vary between ethnic groups. Ethnic-specific percentile charts are currently being used for the assessment of newborns. However, due to globalization and interethnic families, it is unclear which charts should be used. A correlation between a mother's height and her child's BW (1 cm accounts for a 17 g increase in BW) has been observed. The study aims to test differences in small for gestational age (SGA) and large for gestational age (LGA) rates, employing BW percentile charts based on maternal height between ethnic groups. Methods This retrospective study of 2.3 million mother/newborn pairs analyzed BW, gestational age, sex, maternal height and ethnicity from the German perinatal survey (1995-2000). These data were stratified for maternal height (≤157, 158-163, 164-169, 170-175, ≥176 cm) and region of origin (Germany, Central and Northern Europe, North America, Mediterranean region, Eastern Europe, Middle East and North Africa, and Asia excluding Middle East). Percentile charts were calculated for each maternal height group. Results The average BW and maternal height differ significantly between ethnic groups. On current percentile charts, newborns of taller mothers (≥176 cm) have a low rate of SGA and a high rate of LGA, whereas newborns of shorter mothers (≤157 cm) have a high rate of SGA and a low rate of LGA. When the BW data are stratified based on the maternal height, mothers of similar height from different ethnic groups show similar average BWs, SGA and LGA rates. Conclusion Maternal body height has a greater influence on BW than maternal ethnicity. The use of BW percentile charts for maternal height should be considered.

Less invasive surfactant administration is associated with improved pulmonary outcomes in spontaneously breathing preterm infants.

AIM: Providing less invasive surfactant administration (LISA) to spontaneously breathing preterm infants has been reported to reduce mechanical ventilation and bronchopulmonary dysplasia (BPD) in randomised controlled trials. This large cohort study compared these outcome measures between LISA-treated infants and controls. METHODS: Infants receiving LISA, who were born before 32 gestational weeks and enrolled in the German Neonatal Network, were matched to control infants by gestational age, umbilical cord pH, Apgar-score at 5 min, small for gestational age status, antenatal treatment with steroids, gender and highest supplemental oxygen during the first 12 h of life. Outcome data were compared with chi-square and Mann-Whitney U-tests and adjusted for multiple comparisons. RESULTS: Between 2009 and 2012, 1103 infants were treated with LISA at 37 centres. LISA infants had lower rates of mechanical ventilation (41% versus 62%, p < 0.001), postnatal dexamethasone treatment (2.5% versus 7%, p < 0.001), BPD (12% versus 18%, p = 0.001) and BPD or death (14% versus 21%, p < 0.001) than the controls. CONCLUSION: Surfactant treatment of spontaneously breathing infants was associated with lower rates of mechanical ventilation and BPD. Additional large-scale randomised controlled trials are needed to assess the possible long-term benefits of LISA.

Non-invasive spectroscopic determination of the antioxidative status of gravidae and neonates.

Pregnancy and postpartum adaptation cause an increased formation of free radicals. This is associated with various perinatological diseases, e.g. necrotising enterocolitis. The human body has developed a protective system in the form of the antioxidative potential. The present study was the first to investigate the kinetics of the cutaneous antioxidative status in pregnant women and newborns using a non-invasive spectroscopic method. Eighteen pregnant women and their babies took part in the study. A light-emitting diode-based compact scanner system was used for quick non-invasive measurements of carotenoid antioxidants in human skin based on reflection spectroscopy. It could be shown that the antioxidative status of the expectant mothers significantly declined during labour (p < 0.001) and on day 1 after delivery (p < 0.01). Compared to the mothers, the newborns exhibited a significantly higher cutaneous carotenoid concentration on both day 1 (p < 0.01) and 5 (p < 0.01) after delivery. These results suggest that the oxidative stress due to postpartum adaptation is counteracted by an enhanced reservoir of carotenoid antioxidants in the subcutaneous fatty tissue. The peripartum cutaneous carotenoid level of mothers declines continuously, whereas term newborns show very high cutaneous antioxidant values.

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.

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.

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.].