Association between maternal pre-pregnancy body mass index and offspring's outcomes at 9 to 15 years of age.

OBJECTIVE: Maternal pre-pregnancy underweight, overweight and obesity might increase the risk for worse short- and long-term outcome in the offspring. There is a need for further study into the relationship between maternal pre-pregnancy body mass index (BMI) and the combined outcome of physical development, state of health and social behavior in children. QUESTION: Is maternal pre-pregnancy BMI associated with the child outcome in terms of physical development, state of health and social behavior (school and leisure time behavior) at the age of 9 to 15 years? METHODS: In the population-based birth cohort study Survey of Neonates in Pomerania (SNIP) children at the age 9-15 years and their families were re-examined by questionnaire-based follow-up. 5725 mother-child pairs were invited to SNiP-follow-up. This analysis is based on the recall fraction of 24.1% (n = 1379). Based on the maternal pre-pregnancy BMI (ppBMI), 4 groups were formed: underweight (ppBMI < 19 kg/m2, n = 117), normal weight (ppBMI 19-24.99 kg/m2, n = 913, reference), overweight (ppBMI 25-30 kg). /m2, n = 237) and obesity (ppBMI > 30 kg/m2, n = 109). RESULTS: In the multiple regression model, the BMI-z-score for children of mothers in the underweight group was -0.50 lower, and 0.50/1.07 higher in the overweight/obese group (p < 0.001) compared to reference at median age of 12 years. No differences were found in children of underweight mothers with regard to social behavior (interaction with friends and family), school and sports performance (coded from "very good" to "poor"), other leisure activities (watching television, using mobile phones, gaming), and health (occurrence of illnesses) compared to children of normal weight mothers. In contrast, maternal pre-pregnancy overweight and obesity were associated with lower school and sports performance, and higher screen time (smart phone, gaming, television) compared to children of normal weight mothers. CONCLUSION: Maternal pre-pregnancy overweight and obesity but not underweight was negatively associated with school performance and leisure time behavior in the offspring at 9-15 years of age.

Impact of Maternal Pre-Pregnancy Underweight on Cord Blood Metabolome: An Analysis of the Population-Based Survey of Neonates in Pomerania (SNiP).

Intrauterine growth restriction leads to an altered lipid and amino acid profile in the cord blood at the end of pregnancy. Pre-pregnancy underweight is an early risk factor for impaired fetal growth. The aim of this study was to investigate whether a pre-pregnancy body mass index (ppBMI) of <18.5 kg/m2, as early as at the beginning of pregnancy, is associated with changes in the umbilical cord metabolome. In a sample of the Survey of Neonates in Pomerania (SNIP) birth cohort, the cord blood metabolome of n = 240 newborns of mothers with a ppBMI of <18.5 kg/m2 with n = 208 controls (ppBMI of 18.5-24.9 kg/m2) was measured by NMR spectrometry. A maternal ppBMI of <18.5 kg/m2 was associated with increased concentrations of HDL4 cholesterol, HDL4 phospholipids, VLDL5 cholesterol, HDL 2, and HDL4 Apo-A1, as well as decreased VLDL triglycerides and HDL2 free cholesterol. A ppBMI of <18.5 kg/m2 combined with poor intrauterine growth (a gestational weight gain (GWG) < 25th percentile) was associated with decreased concentrations of total cholesterol; cholesterol transporting lipoproteins (LDL4, LDL6, LDL free cholesterol, and HDL2 free cholesterol); LDL4 Apo-B; total Apo-A2; and HDL3 Apo-A2. In conclusion, maternal underweight at the beginning of pregnancy already results in metabolic changes in the lipid profile in the cord blood, but the pattern changes when poor GWG is followed by pre-pregnancy underweight.

Maternal socioeconomic and lifestyle factors and life dissatisfaction associated with a small for gestational age infant. The Survey of Neonates in Pomerania (SNiP).

PURPOSE: The aim is to investigate the associations of the mother's socioeconomic and lifestyle factors and life satisfaction with the delivery of a small for gestational age (SGA) infant. METHODS: Data from 4598 participants of the population-based birth cohort study Survey of Neonates in Pomerania (SniP) including comprehensive information on pregnancies, mothers, and their offspring in Western Pomerania, Germany were used in this study. The associations were analyzed using linear and logistic regression models. RESULTS: After logistic regression analysis adjusted for height of the mother, women who delivered SGA infants, had lower education (p < 0.01) and smoked more frequently during pregnancy (p < 0.01) compared with mothers of adequate for gestational age (AGA) neonates. A mother with less than 10 years of education and one who continued smoking during pregnancy had an odds ratio (OR) of 2.23 [95% confidence interval (CI) = 1.44 to 3.46] and 2.68 (95% CI = 2.06-3.49) of having an SGA infant, respectively. There was no association between the employment of the mother (p = 0.28), the monthly income (p = 0.09), the family status (p = 0.80), the number of friendships outside the household that the mother would not wish to relinquish (p = 0.47), the number of people that she could rely on in case of an emergency (p = 0.75), or alcohol consumption prior to (p = 0.14) or during the pregnancy (p = 0.99) with SGA. Finally, women who delivered SGA infants were more frequently dissatisfied with their employment (p = 0.03) and financial status (p < 0.01). CONCLUSIONS: Women who delivered SGA infants had more associated socioeconomic and lifestyle risk factors and were more frequently dissatisfied with their life conditions than mothers of AGA neonates.

Maternal pre-pregnancy underweight as a risk factor for the offspring: Survey of Neonates in Pomerania.

AIM: The aim was to investigate socio-economic risk factors for maternal underweight before pregnancy and then associations of underweight with neonatal outcomes. METHODS: Data of 3401 mother-child dyads from the population-based birth cohort Survey of Neonates in Pomerania (SNiP) were analysed. RESULTS: Bivariate analysis showed that underweighted mothers were younger, smoked more often, had a lower equivalent income and lower socio-economic status (employment status and/or educational level) compared to women with normal weight. The final prediction model revealed that only younger maternal age (OR = 0.93; 95%-CI = 0.90-0.97) and maternal smoking during pregnancy (OR = 2.52; 95%-CI = 1.74-3.66) were associated with underweight. Compared to women with normal pre-pregnancy BMI, underweight women had an increased chance of premature labour (OR = 1.73; 95% CI: 1.29-2.31) and a reduced placental weight. The offspring of underweight women had an increased risk of late preterm birth (OR = 1.82; 95% CI: 1.21-2.74) and birthweight < 2500 g (OR = 1.91; 95% CI: 1.23-2.95). CONCLUSION: Smoking during pregnancy and a younger age were identified as risk factors for maternal pre-pregnancy underweight which then was associated with late preterm birth and low birthweight.

The neuroendocrine effects of dehydroepiandrosterone and 17ß-estradiol in the in vitro preterm hyperoxia infant model.

Preterm birth causes neurological deficits. Previously, we demonstrated that fetal zone steroids reduce hyperoxia-mediated cell death in vitro. In immature oligodendrocytes (OLN-93 cells), dehydroepiandrosterone + 17ß-estradiol co-treatment had synergistic beneficial effects while signals were transduced through different receptors. In immature astrocytes (C6 cells), both hormones compete for the same receptor and no synergistic effects were observed. 17ß-estradiol and progesterone drastically decrease while fetal zone steroids, mainly dehydroepiandrosterone, remain persistently high within preterm infants until term. Substitution of 17ß-estradiol and progesterone does not improve neurological outcomes. We investigated the influence of dehydroepiandrosterone, 17ß-estradiol or dehydroepiandrosterone + 17ß-estradiol treatment in C6 or OLN-93 cells on steroid receptor availability and activation of intracellular signaling molecules in hyperoxic cell culture. We sought explanations of the observed synergistic effect in preliminary study. In C6 cells, the generated signaling of dehydroepiandrosterone + 17ß-estradiol treatment has no synergistic effects. The combined effect on this particular pathway does not potentiate cell survival. In OLN-93 cells, we observed significant differences in the early generated signaling of 17ß-estradiol + dehydroepiandrosterone treatment to either 17ß-estradiol dehydroepiandrosterone alone but never to both at the same time. The latter finding needs, therefore, further investigation to explain synergistic effects. Nevertheless, we add insight into the receptor and signaling cascade alterations induced by 17ß-estradiol, dehydroepiandrosterone or 17ß-estradiol + dehydroepiandrosterone treatment of C6 and OLN-93 cells in hyperoxia.

Fetal Zone Steroids and Estrogen Show Sex Specific Effects on Oligodendrocyte Precursor Cells in Response to Oxidative Damage.

Oxygen causes white matter damage in preterm infants and male sex is a major risk factor for poor neurological outcome, which speculates the role of steroid hormones in sex-based differences. Preterm birth is accompanied by a drop in 17ß-estradiol (E2) and progesterone along with increased levels of fetal zone steroids (FZS). We performed a sex-based analysis on the FZS concentration differences in urine samples collected from preterm and term infants. We show that, in preterm urine samples, the total concentration of FZS, and in particular the 16α-OH-DHEA concentration, is significantly higher in ill female infants as compared to males. Since we previously identified Nup133 as a novel target protein affected by hyperoxia, here we studied the effect of FZS, allopregnanolone (Allo) and E2 on differentiation and Nup133 signaling using mouse-derived primary oligodendrocyte progenitor cells (OPCs). We show that the steroids could reverse the effect of hyperoxia-mediated downregulation of Nup133 in cultured male OPCs. The addition of FZS and E2 protected cells from oxidative stress. However, E2, in presence of 16α-OH-DHEA, showed a negative effect on male cells. These results assert the importance of sex-based differences and their potential implications in preterm stress response.

Survey of Neonates in Pomerania (SNiP): Study design and cohort update.

BACKGROUND: The health status of newborns is a major concern for parents and medical personnel. Recent studies have provided increasing evidence that factors from the foetal and perinatal periods of life influence health later in life. The "Follow-up of the Survey of Neonates in Pomerania" (SNiP-I-Follow-up) is the first follow-up of the population-based birth cohort study, SNiP-I, established in north-east Germany. OBJECTIVES: The primary aim of SNiP-I-Follow-up study was the collection of longitudinal data on children and adolescents. The associations will be analysed between risk factors in pregnancy and the perinatal period and health status in infancy and later childhood. POPULATION: The population-based cohort study SNiP-I was conducted in Pomerania in north-east Germany between February 2002 and November 2008. All mothers from the SNiP-I birth cohort were recontacted when their children were from 9 to 15 years of age. DESIGN: The SNiP-I-Follow-up study was carried out between December 2016 and August 2017 and is a questionnaire-based survey. METHODS: Physical development, health status, and social behaviour (school and leisure behaviour) of children were analysed using a questionnaire comprising medical, epidemiological, and socio-economic data, associated health care risk factors, and life circumstances of newborns, children, and their parents. PRELIMINARY RESULTS: Out of 5725 children invited to participate in the SNiP-I-Follow-up study between December 2016 and August 2017, 29% (n = 1665) children participated in the SNiP-I-Follow-up study, providing data on 1665 mothers-child dyads. Responders had higher socio-economic status, especially in relation to maternal education status. CONCLUSION: As a longitudinal birth cohort from rural Germany, the SNiP cohort will be a resource to address urgent research needs and contribute to overall population health.

Cost analysis showed that feeding preterm infants with donor human milk was significantly more expensive than mother's milk or formula.

AIM: This study analysed the comparative cost of feeding donor human milk to preterm infants compared to mother's own milk and formula. METHODS: A document and process analysis and a time measurement study were carried out at the milk bank of the Level 1 Perinatal Center of the University Hospital of Greifswald, Germany, from April to June 2017. The cost analysis data were provided by the University's financial department. RESULTS: The total cost per year was €92 085.02 for 300 litres of donor human milk: 27% of this was material costs, 51% was personnel costs, and 22% was other overheads. The average cost per litre was €306.95, and staff time was 492 minutes per litre. The total marginal cost for each additional litre of donor human milk, formula or unpasteurised mother´s milk was €82.88, €10.28 and €38.42, respectively. Pasteurising a litre of donor milk cost €3.51. CONCLUSION: Providing preterm infants with donor milk was much more expensive than using formula or mother's own milk, but the cost of pasteurisation was minimal.

Median urinary iodine concentration reflected sufficient iodine supply in neonates from Northeast Germany in 2005-2006.

PURPOSE: Data from recent adult studies suggest a decline of median urinary iodine concentrations (UIC) in Germany, but since 1996 no German study investigated UIC in neonates. The aim of our study was to investigate UIC and serum thyroid-stimulating hormone (TSH) levels in neonates from Germany. METHODS: We used data from 399 neonates, which were born between April 2005 and November 2006 in the Northeast of Germany. UIC were evaluated by a photometric procedure with Sandell and Kolthoff reaction and afterwards corrected to be comparable with an ICP-MS method. TSH was determined from capillary blood, which was taken within 5 days after birth, by DELFIA. RESULTS: Median UIC were 150 µg/L (25th percentile: 104 µg/L; 75th percentile: 196 µg/L) and differed between boys (153.3 µg/L) and girls (131.5 µg/L; p = 0.012). The prevalence of serum TSH levels > 5 mIU/L was 14%. Neonates from mothers with intake of iodine supplementation (150 µg/L) had significantly higher median UIC than neonates from mothers without iodine supplementation (132 µg/L; p = 0.011). Multivariable linear regression adjusted for sex and iodine supplementation of the mother revealed a significant association between UIC and log-transformed serum TSH levels (ß = 0.003: 95% confidence interval (CI) = 0.0001-0.005; p = 0.028). CONCLUSIONS: Neonates in Northeast Germany did show a sufficient supply of iodine. This points towards the possibility of a sufficient iodine supply of neonates also in other regions of Germany, even though recent studies in adults may indicate mild iodine deficiency.

Analyses of pathological cranial ultrasound findings in neonates that fall outside recent indication guidelines: results of a population-based birth cohort: survey of neonates in Pommerania (SNiP-study).

BACKGROUND: Recent guidelines recommend a cranial ultrasound (CU) in neonates born at < 30 weeks gestation, admitted to the neonatal intensive care unit (NICU), or with a CU indication. Here, we addressed the need to extend these recommendations. METHODS: We retrospectively reviewed 5107 CUs acquired in the population-based Survey of Neonates in Pomerania, conducted in 2002 to 2008. Neonates with conspicuous CUs that were ≥ 30 weeks gestation without recent indications for CU were identified and assigned to the following groups: with (I) or without (II) admission to neonatal care. We designated CU conspicuities as mild (MC) or significant (SC), and we investigated related neurodevelopment during follow-up. RESULTS: Of 5107 neonates, 5064 were born at ≥30 weeks gestation and of those, 4306 received CUs without any indication for this examination. We found conspicuities in 7.7% (n = 47/610) of group I (n = 30 MC, n = 17 SC), and 3.2% (n = 117/3696) of group II (n = 100 MC, n = 17 SC). In group II, SC comprised, e.g., bilateral cysts, partial agenesis of the corpus callosum, and periventricular leukomalacia. Follow-up was available in 75% of infants in group II with MCs and SCs; of these, 12.8% had an abnormal neurological follow-up. CONCLUSIONS: We detected a high number of conspicuities in neonates without a CU indication. However, we could not demonstrate that ultrasound findings were associated with the neurological follow-up or any advantage to an earlier diagnosis. Our data did not support extending current guidelines or a general CU screening policy for all neonates.

Evaluation of neonatal and maternal morbidity in mothers with gestational diabetes: a population-based study.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent complication during pregnancy. Untreated GDM is a severe threat to maternal and neonatal health. Based on recent evidence, up to 15% of all pregnancies may be affected by GDM. We hypothesized that in a rural birth cohort, higher maternal BMI and adverse socioeconomic conditions would promote GDM, which in turn would lead to adverse effects on pregnancy outcomes. METHODS: The current study is a part of a population-based cohort study examining the health and socioeconomic information from 5801 mothers and their children. The study, titled the Survey of Neonates in Pomerania (SNiP), was based in northeastern Pomerania, Germany (2002-2008). RESULTS: The cumulative incidence of GDM was 5.1%. Multiple logistic regression revealed prepregnancy overweight (OR 1.84 (95% CI 1.27-2.68)), prepregnancy obesity (OR 3.67 (2.48-5.44)) and maternal age (OR 1.06 (1.03-1.08)) as risk factors for GDM (p = 0.001). Alcohol use during pregnancy (OR 0.61 (0.41-0.90), a higher monthly income (OR 0.62 (0.46-0.83)), and the highest level of education (OR 0.44 (0.46-0.83)) decreased the risk of GDM. Newborns of GDM mothers had an increased risk of hypoglycaemia (OR 11.71 (7.49-18.30)) or macrosomia (OR 2.43 (1.41-4.18)) and were more often delivered by primary (OR 1.76 (1.21-2.60)) or secondary C-section (OR 2.00 (1.35-2.97)). Moreover, they were born 0.78 weeks (95% CI -1.09 - -0.48 weeks) earlier than infants of mothers without diabetes, resulting in higher percentage of late preterm infants with a gestational age of 32-36 weeks (11.1% vs. 6.96%). CONCLUSIONS: Age and BMI before pregnancy were the predominant mediators of the increased risk of GDM, whereas a higher income and educational level were protective. GDM affected relevant perinatal and neonatal outcomes based on its association with an increased risk of delivery by C-section, preterm birth, macrosomia at birth and neonatal hypoglycaemia.

Physiological adjustment to postnatal growth trajectories in healthy preterm infants.

BACKGROUND: International guidelines suggest that growth of preterm infants should match intrauterine rates. However, the trajectory for extrauterine growth may deviate from the birth percentile due to an irreversible, physiological loss of extracellular fluid during postnatal adaptation to extrauterine conditions. To which "new" physiological growth trajectory preterm infants should adjust to after completed postnatal adaptation is unknown. This study analyzes the postnatal growth trajectories of healthy preterm infants using prospective criteria defining minimal support, as a model for physiological adaptation. METHODS: International, multi-center, longitudinal, observational study at five neonatal intensive care units (NICUs). Daily weights until day of life (DoL) 21 of infants with undisturbed postnatal adaptation were analyzed (gestational ages: (i) 25-29 wk, (ii) 30-34 wk). RESULTS: 981 out of 3,703 admitted infants included. Maximum weight loss was 11% (i) and 7% (ii) by DoL 5, birth weight regained by DoL 15 (i) and 13 (ii). Infants transitioned to growth trajectories parallel to Fenton chart percentiles, 0.8 z-scores below their birth percentiles. The new trajectory after completed postnatal adaptation could be predicted for DoL 21 with R(2) = 0.96. CONCLUSION: This study provides a robust estimate for physiological growth trajectories of infants after undisturbed postnatal adaptation. In the future, the concept of a target postnatal trajectory during NICU care may be useful.

Prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics and outcome in very low birth weight infants.

OBJECTIVE: To evaluate outcome data in an observational cohort of very low birth weight infants of the German Neonatal Network stratified to prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics. STUDY DESIGN: Within the observational period (September 1, 2010, until December 31, 2012, n=5351 infants) study centers were categorized into 3 groups based on their choice of Lactobacillus acidophilus/Bifidobacterium infantis use: (1) no prophylactic use (12 centers); (2 a/b) change of strategy nonuser to user during observational period (13 centers); and (3) use before start of observation (21 centers). Primary outcome data of all eligible infants were determined according to center-specific strategy. RESULTS: The use of probiotics was associated with a reduced risk for necrotizing enterocolitis surgery (group 1 vs group 3: 4.2 vs 2.6%, P=.028; change of strategy: 6.2 vs 4.0%, P<.001), any abdominal surgery, and hospital mortality. Infants treated with probiotics had improved weight gain/day, and probiotics had no effect on the risk of blood-culture confirmed sepsis. In a multivariable logistic regression analysis, probiotics were protective for necrotizing enterocolitis surgery (OR 0.58, 95% CI 0.37-0.91; P=.017), any abdominal surgery (OR 0.7, 95% CI 0.51-0.95; P=.02), and the combined outcome abdominal surgery and/or death (OR 0.43; 95% CI 0.33-0.56; P<.001). CONCLUSIONS: Our observational data support the use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics to reduce the risk for gastrointestinal morbidity but not sepsis in very low birth weight infants.

Management of infants born with severe neonatal alloimmune thrombocytopenia: the role of platelet transfusions and intravenous immunoglobulin.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a fetomaternal incompatibility most commonly induced by maternal anti-HPA-1a alloantibodies. Transfusion of immunologically compatible platelets (PLTs) to prevent cerebral hemorrhage, the most severe complication in affected newborns, is usually recommended. Such PLT concentrates, however, are often not readily available. STUDY DESIGN AND METHODS: The efficacy of random-donor PLT transfusions and intravenous immunoglobulin (IVIG) for the management of 17 neonates across four centers with unexpected, severe NAIT was evaluated. Neonates were treated with random-donor PLTs alone (n=7), random-donor PLTs with IVIG (n=8), or matched HPA-1bb PLTs (n=2). RESULTS: All but one patient (treated with random PLTs and IVIG) achieved a posttransfusion PLT count of higher than 30 × 10(9) /L after the first PLT transfusion. The PLT count remained higher than 30 × 10(9) /L for longer than 24 hours in five of seven, seven of eight, and two of four newborns who received random-donor PLTs alone, random-donor PLTs with IVIG, or matched HPA-1bb PLTs, respectively. None of the newborns developed major bleeding or intracranial hemorrhage. IVIG did not appear to improve either posttransfusion PLT counts or total PLT transfusion requirements. CONCLUSION: Transfusion of random-donor PLTs alone was effective at correcting critically low PLT counts and should be considered as first-line treatment of newborns with unexpected severe NAIT.

IgA response in preterm neonates shows little evidence of antigen-driven selection.

After birth, contact to environmental Ags induces the production of IgA, which represents a first line of defense for the neonate. We sought to characterize the maturation of the repertoire of IgA H chain transcripts in circulating blood B cells during human ontogeny. We found that IgA H chain transcripts were present in cord blood as early as 27 wk of gestation and that the restrictions of the primary Ab repertoire (IgM) persisted in the IgA repertoire. Thus, B cells harboring more "mature" V(H) regions were not preferred for class switch to IgA. Preterm and term neonates expressed a unique IgA repertoire, which was characterized by short CDR-H3 regions, preference of the J(H) proximal D(H)7-27 gene segment, and very few somatic mutations. During the first postnatal months, these restrictions were slowly released. Preterm birth did not measurably accelerate the maturation of the IgA repertoire. At a postconceptional age of 60 wk, somatic mutation frequency of IgA H chain transcripts reached 25% of the adult values but still showed little evidence of Ag-driven selection. These results indicate that similar to IgG, the IgA repertoire expands in a controlled manner after birth. Thus, the IgA repertoire of the newborn has distinctive characteristics that differ from the adult IgA repertoire. These observations might explain the lower affinity and specificity of neonatal IgA Abs, which could contribute to a higher susceptibility to infections and altered responses to vaccinations, but might also prevent the development of autoimmune and allergic diseases.

Eating problems in very low birthweight children are highest during the first year and independent risk factors include duration of invasive ventilation.

AIM: This study aimed to investigate the incidence and time course of eating problems in children born with a very low birthweight (VLBW) and to identify the perinatal risk factors. METHODS: We used a standard eating questionnaire to study 178 VLBW children, born between 1999 and 2005 at a median of 28.6 weeks' gestation and median birthweight of 1058 g, for the first 6 years of life. The control group comprised 74 children born full term. RESULTS: Just under a quarter of the VLBW children (24.7%) had eating problems before the age of one, and by the age of two, the cumulative incidence had increased to 28.6%. The 69 children born between 1999 and 2001 had eating problems up to the age of six, but 76.5% were resolved by the age of four. Independent risk factors were gestational age at birth, and duration of invasive ventilation and eating problems were associated with significantly poor growth. CONCLUSION: The incidence of eating problems in VLBW children was highest during the first year of life. Gestational age and the duration of invasive ventilation were independent risk factors, and eating problems contributed to continued growth failure. Eating problems require early recognition and intervention.

Steroid Metabolomic Signature in Term and Preterm Infants.

Adrenal function is essential for survival and well-being of preterm babies. In addition to glucocorticoids, it has been hypothesized that C19-steroids (DHEA-metabolites) from the fetal zone of the adrenal gland may play a role as endogenous neuroprotective steroids. In 39 term-born (≥37 weeks gestational age), 42 preterm (30-36 weeks) and 51 early preterm (<30 weeks) infants 38 steroid metabolites were quantified by GC-MS in 24-h urinary samples. In each gestational age group, three distinctive cluster were identified by pattern analysis (k-means clustering). Individual steroidal fingerprints and clinical phenotype were analyzed at the 3rd day of life. Overall, the excretion rates of C21-steroids (glucocorticoid precursors, cortisol, and cortisone metabolites) were low (<99 µg/kg body weight/d) whereas the excretion rates of C19-steroids were up to 10 times higher. There was a shift to higher excretion rates of C19-steroids in both preterm groups compared to term infants but only minor differences in the distribution of C21-steroids. Comparable metabolic patterns were found between gestational age groups: Cluster 1 showed mild elevation of C21- and C19-steroids with the highest incidence of neonatal morbidities in term and severe intraventricular hemorrhage in early preterm infants. In cluster 2 lowest excretion in general was noted but no clinically unique phenotype. Cluster 3 showed highest elevation of C21-steroids and C19-steroids but no clinically unique phenotype. Significant differences in steroid metabolism between clusters are only partly reflected by gestational age and disease severity. In early preterm infants, higher excretion rates of glucocorticoids and their precursors were associated with severe cerebral hemorrhage. High excretion rates of C19-steroids in preterm infants may indicate a biological significance.

Antenatal Care and Health Behavior of Pregnant Women-An Evaluation of the Survey of Neonates in Pomerania.

BACKGROUND: The German maternity guidelines require regular medical checkup (MC) during pregnancy as a measure of prevention. Socioeconomic factors such as education, profession, income and origin, but also age and parity may influence the preventive and health behavior of pregnant women. The aim was to investigate the influence of these factors on the participation rate in MC of pregnant women. METHOD: The current analysis is based on the prospective population-based birth cohort study Survey of Neonates in Pomerania, which was conducted in Western Pomerania, Germany. The data of 4092 pregnant women from 2004 to 2008 were analyzed regarding the antenatal care and health behavior. Up to 12 MC were regularly offered; participation in 10 MC is defined as standard screening according to maternity guidelines. RESULTS: Women participated in the first preventive MC on average in the 10th (±3.8 SD) week of pregnancy. 1343 (34.2%) women participated in standard screening and 2039 (51.9%) took a screening above standard. 547 (13.92%) women participated in less than the 10 standard MCs. In addition, about one-third of the pregnancies investigated in this study were unplanned. Bivariate analyses showed an association between better antenatal care behavior and higher maternal age, stabile partnerships and mother born in Germany, p < 0.05. On the contrary antenatal care below standard were more often found by women with unplanned pregnancies, less educational women and women with lower equivalent income, p < 0.001. Health behaviors also influenced antenatal care. Whereas the risk of antenatal care below standard increased by smoking during pregnancy (RRR 1.64; 95% CI 1.25, 2.14) and alcohol consumption (RRR 1.31; 95% CI 1.01, 1.69), supplementation intake was associated with decreased risk (iodine-RRR 0.66; 95% CI 0.53, 0.81; folic acid-RRR 0.56; 95% CI 0.44, 0.72). The health behavior of pregnant women also differs according to their social status. Higher maternal income was negatively correlated with smoking during pregnancy (OR 0.2; 95% CI 0.15, 0.24), but positively associated with alcohol consumption during pregnancy (OR 1.3; 95% CI 1.15, 1.48) and lower pre-pregnancy BMI (Coef. = 0.083, p < 0.001). Lower maternal education was positively correlated with smoking during pregnancy (OR 59.0; 95% CI 28.68, 121.23). CONCLUSIONS: Prenatal care according to maternity guidelines is well established with a high participation rate in MC during pregnancy of more than 85%. However, targeted preventive measures may address younger age, socioeconomic status and health-damaging behaviors (smoking, drinking) of the pregnant women because these factors were associated with antenatal care below standard.

Ecological momentary assessment of parent-child attachment via technological devices: A systematic methodological review.

Despite extensive research about parent-child attachment using observational and self-report studies, complementary measures are needed to assess this construct objectively with ecological validity, as well as less obtrusiveness and reactivity than traditional measures. This systematic review describes existing technology-based ecologically momentary assessment (EMA) tools examining attachment-related emotions, cognition, and behaviors between the child and its parents. From the study's inception until March 2021, four databases were searched resulting in 11,910 screened citations. Finally, 18 records were included, characterized by a broad variety of assessment tools, sample characteristics, study designs, and attachment outcomes. Technology-based EMA methods comprised audio, video, diary, and sensory assessment modalities, each occuying its methodological niche. When reported, the psychometric properties of the EMA methods were evaluated as very good; however, the included studies' psychometric data was not completely examined. The main attachment outcomes assessed by EMA were emotional and cognitive reactions and actions of the children, the parents, and the dyad. Cognition was rarely assessed using EMA methods. Future research should focus on the complexity of attachment considering different ethnic backgrounds, multiple caregivers' viewpoints, gender aspects, as well as cognitive and dyadic contents in the naturalistic environment.

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. The effect of indomethacin prophylaxis on outcomes was analyzed in univariate analyses and multivariate regression models including a subgroup of infants with available data on 5-year follow-up. RESULTS: 4760 infants were included with a median gestational age of 24.6 SSW [interquartile range (IQR) 24.1w-25.2w] and a birth weight of 640 g [IQR 550-750 g]. 1767/4760 (37.1%) preterm infants were born in the context of AIS and 527/4760 (11.1%) received indomethacin prophylaxis. AIS infants receiving prophylactic indomethacin had lower rates of IVH (32.7% vs. 36.9%, p = 0.04), IVH III/IV (9.7% vs. 16.0%, p = 0.02) and the combined outcome of severe IVH or death (15.9% vs. 23.2%, p = 0.01) as compared to infants without prophylaxis. Multivariate logistic regression analyses confirmed our observations. In a subgroup analysis of 730 preterm infants at 5 years of age, we did not find any correlation between prophylactic indomethacin and intelligence quotient <70 or cerebral palsy. CONCLUSIONS: Our observational data demonstrate that prophylactic indomethacin is associated with a reduced risk of IVH in the highly vulnerable subgroup of preterm infants <26 weeks of gestation born from AIS.