Associations of maternal inflammatory states with human milk composition in mothers of preterm infants.

Introduction: Overweight/obesity (ow/ob) is increasing in prevalence in pregnant women, and it is associated with other pro-inflammatory states, such as pre-eclampsia, gestational diabetes, and preterm labor. Data are lacking if mothers experiencing inflammatory states who deliver preterm have mother's own milk (MOM) with differing inflammatory markers or pro-inflammatory fatty acid (FA) profiles. Methods: The aim was to explore associations of maternal pre- and perinatal inflammatory states with levels of inflammatory markers and/or FAs in longitudinal samples of MOM from mothers of preterm infants born <1,250 g. Inflammatory states included pre-pregnancy ow/ob, diabetes, chorioamnionitis (chorio), preterm labor (PTL), premature rupture of membranes (PROM), pre-eclampsia, and cesarian delivery. In MOM, inflammatory markers studied included c-reactive protein (CRP), free choline, IFN-Ɣ, IL-10, IL-1ß, IL-1ra, IL-6, IL-8, and TNF-α, and FAs included omega-6:omega-3 ratio, arachidonic acid, docosahexaenoic acid, linoleic acid, monounsaturated FAs, and saturated FAs. The above inflammatory states were assessed individually, and the healthiest mothers (normal BMI, no chorio, and ± no pre-eclampsia) were grouped. Regression analysis tested associations at baseline (day 5) and over time using generalized estimating equations. Results: A total of 92 infants were included who were delivered to mothers (42% ow/ob) at a median gestational age of 27.7 weeks and birth weight of 850 g. MOM CRP was 116% higher (relative change 2.16) in mothers with ow/ob at baseline than others (p = 0.01), and lower (relative change 0.46, 0.33, respectively) in mothers in the two "healthy groups" at baseline (both p < 0.05) than others. MOM IL-8 levels were lower with chorio and PTL at baseline. No significant associations were found for other individual or grouped inflammatory states nor for other MOM inflammatory markers nor FA profiles at baseline. Discussion: In conclusion, MOM CRP levels are positively associated with inflammatory states, such as ow/ob. Reassuringly, there was no association between FA profiles or most other inflammatory markers and maternal inflammatory states. Further studies are needed to determine potential associations or ramifications of MOM CRP in vulnerable preterm infants.

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.

Individualized birth length and head circumference percentile charts based on maternal body weight and height.

Objectives Measurement of birth length and birth head circumference is part of the newborn assessment. Both measurements aid in distinguishing between proportionate and disproportionate small and large for gestational age newborns. It had been shown that birth weight is related to maternal height and weight. This study aims to analyze birth length and birth head circumference percentiles based on maternal stature. Methods This observational study analyzed birth length and birth head circumference percentiles of 2.3 million newborns stratified by maternal height and weight from the first obstetric assessment. Percentiles were calculated for sex and 22-43 gestational weeks for all infants. Eighteen subgroups based on six maternal height and three weight strata were defined and percentiles calculated from 32 to 42 gestational weeks using GAMLSS package for R. Results Newborns of mothers with height <158 cm and weight <53 kg (short stature) had a rate of preterm birth of 9%, compared to 5% in the tall stature group (height >177 cm, weight >79 kg). Small stature mothers were 1.7 years younger. Birth length differed by several centimeters for the same percentiles between groups of short and tall stature mothers, whereas birth head circumference differed up to 1.2 cm. The largest deviation of birth length was between the 97th percentiles. For male newborns born at term, birth length at the 97th percentile differed by 3.2 cm, at the 50th percentile by 2.7 cm and at the third percentile by 2.5 cm. Conclusions Birth length and birth head circumference are related to maternal height and weight. To more completely assess newborns, the maternal size should be considered.

Z-score differences based on cross-sectional growth charts do not reflect the growth rate of very low birth weight infants.

OBJECTIVE: To test whether the assessment of growth in very low birth weight infants during the hospital stay using z-score differences (Zdiff) is confounded by gestational age (GA), birth weight percentiles (BW%ile), and length of the observation period (LOP). We hypothesize that Zdiff calculated from growth charts based on birth weight data introduces a systematic statistical error leading to falsely classified growth as restricted in infants growing similarly to the 50th percentile. METHODS: This observational study included 6,926 VLBW infants from the German Neonatal Network (2009 to 2015). Inclusion criterion was discharge between 37 and 41 weeks postmenstrual age. For each infant, Zdiff, weight gain velocity, and reference growth rate (50th percentile Fenton) from birth to discharge were calculated. To account for gestational age dependent growth rates, assessment of growth was standardized calculating the weight gain ratio (WGR) = weight gain velocity/reference growth rate. The primary outcome is the variation of the Zdiff-to-WGR relationship. RESULTS: Zdiff and WGR showed a weak agreement with a Zdiff of -0.74 (-1.03, -0.37) at the reference growth rate of the 50th percentile (WGR = 1). A significant proportion (n = 1,585; 23%) of infants with negative Zdiff had weight gain velocity above the 50th percentile's growth rate. Zdiff to WGR relation was significantly affected by the interaction of GA x BW%ile x LOP. CONCLUSION: This study supports the hypothesis that Zdiff, which are calculated using birth weights, are confounded by skewed reference data and can lead to misinterpretation of growth rates. New concepts like individualized growth trajectories may have the potential to overcome this limitation.

Individualized Postnatal Growth Trajectories for Preterm Infants.

BACKGROUND: Growth of preterm infants is monitored using fetal charts despite individual trajectories being downshifted postnatally by adaptational processes. The study aims to compare different approaches to create individualized postnatal trajectories. METHODS: Three approaches to achieve growth similar to healthy term infants at 42+0/7 weeks postmenstrual age (PMA) on World Health Organization growth standards (WHOGS) (target weight) were tested by comparing trajectories obtained by: 1) following birth percentiles (Birth-Weight-Percentile Approach); 2) following percentiles achieved at day of life 21 (Postnatal-Percentile Approach); 3) using day-specific fetal median growth velocities starting at day of life 21 (Fetal-Median-Growth Approach [FMGA]). The primary outcome was delta weight (ΔW), defined as difference between target weight (WHOGS) at 42+0/7 weeks and weight predicted by trajectories. The secondary outcome was ΔW vs %fat mass in a cohort of 20 disease-free surviving very low-birth-weight infants. RESULTS: Birth-Weight-Percentile and Postnatal-Percentile Approach showed high ΔW; FMGA alone reduced ΔW. Introducing a factor to FMGA to reflect the transition to extrauterine conditions (Growth-Velocity Approach [GVA]) minimized ΔW. GVA merged with target and best normalized for body composition related to ΔW. CONCLUSIONS: GVA provides an evidence-based approach for individualized growth trajectories. GVA is based on physiologic data and that healthy preterm infants adjust their postnatal trajectory below their birth percentile. GVA may reflect a biologic principle because it matches consistently with WHOGS at 42+0/7 weeks for all preterm infants from 24 to 34 weeks. This concept could become a bedside tool to aid clinicians in monitoring growth, guiding nutrition, and minimizing chronic adult disease risks as a consequence of unguided, inappropriate growth.

Quality Indicators but Not Admission Volumes of Neonatal Intensive Care Units Are Effective in Reducing Mortality Rates of Preterm Infants.

AIM: To investigate how two different strategies to form larger neonatal intensive care units (NICU) impact neonatal mortality rates. METHODS: Cross-sectional study modeling admission volumes and mortality rates of 177,086 VLBW infants aggregated into 862 NICUs. Cumulative 3-year data was abstracted from Vermont Oxford Network. The model simulated a reduction in number of NICUs by stepwise exclusion using either admission volume (VOL) or quality (QUAL) cut-offs. After randomly redirecting infants of excluded to remaining NICUs resulting system mortality rates were calculated with and without adjusting for effects of experience levels (EL) using published data to reflect effects of different team-to-patient exposure. RESULTS: The quality-based strategy is more effective in reducing mortality; while VOL alone was not able to reduce system mortality, QUAL already achieved a 5% improvement after reducing 8% of NICUs and redirecting 6% of infants. Including "EL", a 5% improvement of mortality was achieved by reducing 77% (VOL) vs. 7% (QUAL) of NICUs and redirecting 54% (VOL) vs. 5% (QUAL) of VLBW infants, respectively. CONCLUSION: While a critical number of admissions is needed to maintain skills this study emphasizes the importance of including quality parameters to restructure neonatal care. The findings can be generalized to other medical fields.

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.

Challenges in breast milk fortification for preterm infants.

PURPOSE OF REVIEW: To outline new evidence published from 2013 to 2014 about breast milk fortification in preterm infants. RECENT FINDINGS: Breast milk is the feeding choice for preterm infants because of its immunoprotective properties. However, breast milk's nutrient content is not sufficient for preterm infants, and interindividual variation is high. The variation challenges standard fortification, which assumes a standard breast milk composition. Two new fortification strategies (adjustable fortification and target fortification) optimize macronutrient intake and improve growth. Adjustable fortification uses blood urea nitrogen levels to adjust fortifier strength. Target fortification analyzes breast milk and fortifies macronutrients individually to achieve targeted intake. Its feasibility is shown in clinical routine. Current breast milk analyzers used for target fortification achieve acceptable precision for protein and fat but not for lactose and energy. Evidence of benefits for postdischarge breast milk fortification is lacking. Eliminating cow's milk products and feeding exclusively breast milk may decrease the occurrence of feeding intolerance and necrotizing enterocolitis. To facilitate exclusively breast milk diets, a collaboration of prenatal, nutrition and lactation stakeholders is key. Fortification increases osmolality; however, safety cutoffs to prevent necrotizing enterocolitis are unclear. There is also new evidence that composition and structure of various macronutrients and micronutrients affect growth and development, and might play a role in future fortification concepts. SUMMARY: Recent research focuses on the variability of breast milk composition, its impact on postnatal growth patterns and the usefulness of target fortification. As well, diets exclusively composed of human milk are a promising approach to improve feeding tolerance. For safe fortification, osmolality cutoff levels are needed.