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The power of continuous glucose monitoring system (CGMS) technology to profile glycemic patterns throughout a 24-h period has benefited the care of individuals with diabetes mellitus for over 10 years. Recently, this technology has been utilized to better understand glucose patterns in pregnancy, especially as they relate to abnormal fetal growth given that adiposity at birth is associated with increased risks for childhood obesity and metabolic syndrome. However, the lack of a standardized approach to defining glucose measures associated with maternal outcomes and fetal growth has greatly limited comparison and pooling of CGMS data among pregnancy trials, hindering our ability to take advantage of the enormous amount of data available to explore these relationships. The purpose of this article is to offer a methodical approach to the identification and extraction of CGMS-derived glucose variables for the characterization of glycemic profiles in pregnant women, particularly focusing on women with gestational diabetes or obesity who are at risk for abnormal fetal growth. A review of the properties of CGMS data and examples of how CGMS data in pregnancy have been reported to date are included. We further define several pregnancy-relevant, CGMS-derived glucose variables and directly apply them to unpublished data to illustrate how these measures might be utilized. This approach offers one possible standardized method to define and analyze these time-sensitive glucose measures to facilitate comparisons among studies and to increase our understanding of how glycemic profiles contribute to excess infant adiposity in pregnant women with and without diabetes. [ABSTRACT FROM AUTHOR]

Objective: We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy.Research Design and Methods: Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured.Results: The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P < 0.05), and late fasting insulin (r = 0.49, P < 0.05) correlated with infant percentage body fat. However, early fasting triglycerides (r = 0.67, P < 0.001) and late fasting FFAs (r = 0.54, P < 0.01) were even stronger correlates.Conclusions: This is the first study to demonstrate that obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth. [ABSTRACT FROM AUTHOR]

BACKGROUND: Little is known about the comparative effect of weight-loss diets on metabolic profiles during dieting. OBJECTIVE: The purpose of this study was to compare the effect of a low-carbohydrate diet (< or =20 g/d) with a high-carbohydrate diet (55% of total energy intake) on fasting and hourly metabolic variables during active weight loss. DESIGN: Healthy, obese adults (n = 32; 22 women, 10 men) were randomly assigned to receive either a carbohydrate-restricted diet [High Fat; mean +/- SD body mass index (BMI; in kg/m(2)): 35.8 +/- 2.9] or a calorie-restricted, low-fat diet (High Carb; BMI: 36.7 +/- 4.6) for 6 wk. A 24-h in-patient feeding study was performed at baseline and after 6 wk. Glucose, insulin, free fatty acids (FFAs), and triglycerides were measured hourly during meals, at regimented times. Remnant lipoprotein cholesterol was measured every 4 h. RESULTS: Patients lost a similar amount of weight in both groups (P = 0.57). There was an absence of any diet treatment effect between groups on fasting triglycerides or on remnant lipoprotein cholesterol, which was the main outcome. Fasting insulin decreased (P = 0.03), and both fasting (P = 0.040) and 24-h FFAs (P < 0.0001) increased within the High Fat group. Twenty-four-hour insulin decreased (P < 0.05 for both groups). Fasting LDL cholesterol decreased in the High Carb group only (P = 0.003). In both groups, the differences in fasting and 24-h FFAs at 6 wk were significantly correlated with the change in LDL cholesterol (fasting FFA: r = 0.41, P = 0.02; 24-h FFA: r = 0.52, P = 0.002). CONCLUSIONS: Weight loss was similar between diets, but only the high-fat diet increased LDL-cholesterol concentrations. This effect was related to the lack of suppression of both fasting and 24-h FFAs. © 2010 American Society for Nutrition. [ABSTRACT FROM AUTHOR]

Background: Fasting glucose is higher in pregnancies with obesity (OB); less is known about postprandial (PP) and nocturnal patterns when the diet is eucaloric and fixed or about the continuous-glucose-monitor (CGM) metrics that predict neonatal adiposity (NB%fat). We hypothesized that continuous glucose monitors (CGMs) would reveal higher glycemia in OB vs. normal weight (NW) during Early (14-16 weeks) and Later (26-28 weeks) gestation despite macronutrient-controlled eucaloric diets and elucidate unique predictors of NB%fat., Methods: In a prospective, parallel-group comparative study, a eucaloric diet (NW: 25 kcal/kg; OB: 30 kcal/kg) was provided (50% carbohydrate [20% simple/30% complex; of total calories], 35% fat, 15% protein) to Early and Later gestation groups wearing a blinded CGM for three days. CGM metrics (mean fasting; 1 h and 2 h PP; daytime and nocturnal glucose; percent time-in-range (%TIR: 63-140 mg/dL); PP excursions; and area-under-the-curve [AUC]) were interrogated between groups and as predictors of NB%fat by dual X-ray absorptiometry(DXA)., Results: Fifty-four women with NW (BMI: 23 kg/m 2 ; n = 27) and OB (BMI: 32; n = 27) provided their informed consent to participate. Early, the daytime glucose was higher in OB vs. NW (mean ± SEM) (91 ± 2 vs. 85 ± 2 mg/dL, p = 0.017), driven by 2 h PP glucose (95 ± 2 vs. 88 ± 2, p = 0.004). Later, those with OB exhibited higher nocturnal (89 ± 2 vs. 81 ± 2), daytime (95 ± 2 vs. 87 ± 2), 1 h (109 ± 3 vs. 98 ± 2), and 2 h PP (101 ± 3 vs. 92 ± 2) glucose (all p < 0.05) but no difference in %TIR (95-99%). Postprandial peak excursions for all meals were markedly blunted in both the Early (9-19 mg/dL) and Later (15-26 mg/dL). In OB, the Later group's 24 h AUC was correlated with NB%fat (r = 0.534, p = 0.02). Despite similar weight gain, infants of OB had higher birthweight (3528 ± 107 vs. 3258 ± 74 g, p = 0.037); differences in NB%fat did not reach statistical significance (11.0 vs. 8.9%; p > 0.05)., Conclusions: Despite macronutrient-controlled eucaloric diets, pregnancies with OB had higher glycemia Early and Later in gestation; the Later 24 h glucose AUC correlated with NB%fat. However, glycemic patterns were strikingly lower than current management targets.

Urine serotonin (5-HT)/creatinine was lower at day of life 3 in newborns with pulmonary hypertension compared with controls, while the percent change in the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA)/creatinine increased. We speculate that the changes in 5-HT and 5-HIAA reflect enhanced pulmonary 5-HT uptake and/or metabolism., Competing Interests: Declaration of Competing Interest Financial support was provided by the National Organization for Rare Disorders193996 (to C.G.). The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gestational diabetes remains the most common medical disorder in pregnancy, with short-term and long-term consequences for mothers and offspring. New insights into pathophysiology and management suggest that the current gestational diabetes treatment approach should expand from a focus on late gestational diabetes to a personalised, integrated life course approach from preconception to postpartum and beyond. Early pregnancy lifestyle intervention could prevent late gestational diabetes. Early gestational diabetes diagnosis and treatment has been shown to be beneficial, especially when identified before 14 weeks of gestation. Early gestational diabetes screening now requires strategies for integration into routine antenatal care, alongside efforts to reduce variation in gestational diabetes care, across settings that differ between, and within, countries. Following gestational diabetes, an oral glucose tolerance test should be performed 6-12 weeks postpartum to assess the glycaemic state. Subsequent regular screening for both dysglycaemia and cardiometabolic disease is recommended, which can be incorporated alongside other family health activities. Diabetes prevention programmes for women with previous gestational diabetes might be enhanced using shared decision making and precision medicine. At all stages in this life course approach, across both high-resource and low-resource settings, a more systematic process for identifying and overcoming barriers to preventative care and treatment is needed to reduce the current global burden of gestational diabetes., Competing Interests: Declaration of interests DS received study devices on loan from Tandem for the CIRCUIT study and speaker fees from Ascensia and Sanofi. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Gestational diabetes mellitus (GDM) triggers alterations in the maternal microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. We investigated maternal microbiome-metabolomic changes, including over 600 metabolites from a subset of the "Choosing Healthy Options in Carbohydrate Energy" (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n = 18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n = 16, 40% carbohydrate/45% fat/15% protein). All meals were provided. Diets were eucaloric, and fiber content was similar. CHOICE was associated with increases in trimethylamine N-oxide, indoxyl sulfate, and several triglycerides, while CONV was associated with hippuric acid, betaine, and indole propionic acid, suggestive of a healthier metabolome. Conversely, the microbiome of CHOICE participants was enriched with carbohydrate metabolizing genes and beneficial taxa such as Bifidobacterium adolescentis , while CONV was associated with inflammatory pathways including antimicrobial resistance and lipopolysaccharide biosynthesis. We also identified latent metabolic groups not associated with diet: a metabolome associated with less of a decrease in fasting glucose, and another associated with relatively higher fasting triglycerides. Our results suggest that GDM diets produce specific microbial and metabolic responses during pregnancy, while host factors also play a role in triglycerides and glucose metabolism.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic created disruption in health care delivery, including a sudden transition to telehealth use in mid-March 2020. The purpose of this study was to examine changes in the mode of prenatal care visits and predictors of telehealth use (provider-patient messaging, telephone visits, and video visits) during the COVID-19 pandemic among those receiving care in a large, academic nurse-midwifery service., Methods: We conducted a retrospective cohort study of those enrolled for prenatal care in 2 nurse-midwifery clinics between 2019 and 2021 (n = 3172). Use outcomes included number and type of encounter: in-person and telehealth (primary outcome). Comparisons were made in frequency and types of encounters before and during COVID-19. A negative binomial regression was fit on the outcome of telehealth encounter count, with race/ethnicity, age, language, parity, hypertension, diabetes, and depression as predictors., Results: When comparing pre-COVID-19 (before March 2020) with during COVID-19 (after March 2020), overall encounters increased from 15.9 to 19.5 mean number of encounters per person (P < .001). The increase was driven by telehealth encounters; there were no significant differences for in-person prenatal visit counts before and during the pandemic period. Direct patient-provider messaging was the most common type of telehealth encounter. Predictors of telehealth encounters included English as primary language and diagnoses of diabetes or depression., Discussion: No differences in the frequency of in-person prenatal care visits suggests that telehealth encounters led to more contact with midwives and did not replace in-person encounters. Spanish-speaking patients were least likely to use telehealth-delivered prenatal care during the pandemic; a small, but significant, proportion of patients had no or few telehealth encounters, and a significant proportion had high use of telehealth. Integration of telehealth in future delivery of prenatal care should consider questions of equity, patient and provider satisfaction, access, redundancies, and provider workload., (© 2023 by the American College of Nurse‐Midwives.)

Background: Optimizing care during labor protraction is a key strategy for reducing cesareans, especially among people with obesity. The pathophysiology of labor dystocia remains poorly understood, limiting precise interventions targeting the cause of protraction., Methods: In this secondary analysis of nulliparas (n = 92) with obesity (BMI ≥ 30 kg/m 2 ) and spontaneous labor onset, we classified labor into four phenotypes based on duration of protraction and birth route: (1) no protraction, (2) short protraction and vaginal birth, (3) extended protraction meeting criteria for labor arrest, but with eventual progression and vaginal birth, and (4) extended protraction meeting criteria for labor arrest and cesarean birth. Across these phenotypes, we compared MVU, oxytocin dose, and novel measures of uterine responsiveness to oxytocin augmentation (MVU to oxytocin dose ratios)., Results: In our sample, phenotype group 1 comprised 14.1% (n = 13); group 2 comprised 30.4% (n = 28); group 3 comprised 34.8% (n = 32); and group 4 comprised 20.7% (n = 19). Uterine responsiveness to oxytocin, but not MVU, decreased with each labor phenotype. Participants with cesarean birth had the lowest uterine responsiveness to oxytocin., Conclusion: Labor and birth outcomes were associated with measures of uterine responsiveness to oxytocin rather than MVU alone, and thus these may be more clinically appropriate measures for guiding clinical decision-making. Current criteria for labor arrest are likely too stringent for nulliparas with obesity, many of whom appear to progress to safe vaginal birth after longer labor durations. Differences in uterine responsiveness to oxytocin augmentation across the groups suggests underlying physiologic differences in the labor phenotypes, which should drive future research targeting pathophysiology., (© 2023 Wiley Periodicals LLC.)

Introduction: Human milk delivers critical nutritional and immunological support to human infants. Milk fat globules (MFGs) and their associated membranes (MFGMs) contain the majority of milk lipids and many bioactive components that contribute to neonatal development and health, yet their compositions have not been fully defined, and the mechanisms responsible for formation of these structures remain incompletely understood. Methods: In this study, we used untargeted mass spectrometry to quantitatively profile the protein compositions of freshly obtained MFGs and their paired, physically separated MFGM fractions from 13 human milk samples. We also quantitatively profiled the MFG protein compositions of 9 pooled milk samples from 18 lactating mouse dams. Results: We identified 2,453 proteins and 2,795 proteins in the majority of human MFG and MFGM samples, respectively, and 1,577 proteins in mouse MFGs. Using paired analyses of protein abundance in MFGMs compared to MFGs (MFGM-MFG; 1% FDR), we identified 699 proteins that were more highly abundant in MFGMs (MFGM-enriched), and 201 proteins that were less abundant in MFGMs (cytoplasmic). MFGM-enriched proteins comprised membrane systems (apical plasma membrane and multiple vesicular membranes) hypothesized to be responsible for lipid and protein secretion and components of membrane transport and signaling systems. Cytoplasmic proteins included ribosomal and proteasomal systems. Comparing abundance between human and mouse MFGs, we found a positive correlation ( R 2 = 0.44, p < 0.0001) in the relative abundances of 1,279 proteins that were found in common across species. Discussion: Comparative pathway enrichment analyses between human and mouse samples reveal similarities in membrane trafficking and signaling pathways involved in milk fat secretion and identify potentially novel immunological components of MFGs. Our results advance knowledge of the composition and relative quantities of proteins in human and mouse MFGs in greater detail, provide a quantitative profile of specifically enriched human MFGM proteins, and identify core cellular systems involved in milk lipid secretion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martin Carli, Dzieciatkowska, Hernandez, Monks and McManaman.)

Objective: Nutrition therapy for gestational diabetes mellitus (GDM) has conventionally focused on carbohydrate restriction. In a randomized controlled trial (RCT), we tested the hypothesis that a diet (all meals provided) with liberalized complex carbohydrate (60%) and lower fat (25%) (CHOICE diet) could improve maternal insulin resistance and 24-h glycemia, resulting in reduced newborn adiposity (NB%fat; powered outcome) versus a conventional lower-carbohydrate (40%) and higher-fat (45%) (LC/CONV) diet., Research Design and Methods: After diagnosis (at ∼28-30 weeks' gestation), 59 women with diet-controlled GDM (mean ± SEM; BMI 32 ± 1 kg/m2) were randomized to a provided LC/CONV or CHOICE diet (BMI-matched calories) through delivery. At 30-31 and 36-37 weeks of gestation, a 2-h, 75-g oral glucose tolerance test (OGTT) was performed and a continuous glucose monitor (CGM) was worn for 72 h. Cord blood samples were collected at delivery. NB%fat was measured by air displacement plethysmography (13.4 ± 0.4 days)., Results: There were 23 women per group (LC/CONV [214 g/day carbohydrate] and CHOICE [316 g/day carbohydrate]). For LC/CONV and CHOICE, respectively (mean ± SEM), NB%fat (10.1 ± 1 vs. 10.5 ± 1), birth weight (3,303 ± 98 vs. 3,293 ± 81 g), and cord C-peptide levels were not different. Weight gain, physical activity, and gestational age at delivery were similar. At 36-37 weeks of gestation, CGM fasting (86 ± 3 vs. 90 ± 3 mg/dL), 1-h postprandial (119 ± 3 vs. 117 ± 3 mg/dL), 2-h postprandial (106 ± 3 vs. 108 ± 3 mg/dL), percent time in range (%TIR; 92 ± 1 vs. 91 ± 1), and 24-h glucose area under the curve values were similar between diets. The %time >120 mg/dL was statistically higher (8%) in CHOICE, as was the nocturnal glucose AUC; however, nocturnal %TIR (63-100 mg/dL) was not different. There were no between-group differences in OGTT glucose and insulin levels at 36-37 weeks of gestation., Conclusions: A ∼100 g/day difference in carbohydrate intake did not result in between-group differences in NB%fat, cord C-peptide level, maternal 24-h glycemia, %TIR, or insulin resistance indices in diet-controlled GDM., (© 2023 by the American Diabetes Association.)

Background: Maternal obesity and cesarean birth disproportionately affect Black parturients; thus, prevention of cesarean birth is a key modifiable factor to improve pregnancy outcomes and reduce disparities. The primary driver of unplanned cesarean birth among people with higher body mass index is prolonged labor duration. However, strategies to optimize outcomes in these situations have not been established. We aimed to evaluate the influence of oxytocin augmentation on uterine activity and labor progression in nulliparas with obesity., Methods: This secondary analysis involved nulliparas with obesity (BMI ≥30 kg/m 2 ) who had spontaneous labor onset followed by oxytocin augmentation and an intrauterine pressure catheter. Using Linear Mixed Models, we evaluated relationships between uterine activity measured in Montevideo units (MVU), oxytocin dose, and rate of cervical dilation normalized by labor duration., Results: In this diverse sample (35.6% Caucasian, 16.11% African American, 40.2% Hispanic) of nulliparas with obesity ( n = 87; BMI 35.54 ± 4.38 kg/m 2 ), 31% ended labor with cesarean birth. Among those with vaginal birth, only 13% had MVU ≥200 prior to the final 2 hours of labor. MVUs were only minimally responsive to oxytocin dose and were not associated with labor progression nor birth route., Conclusion: MVU measurements may not be useful to diagnose labor arrest in nulliparas with obesity. Optimizing care for birthing people with obesity is essential for improving perinatal outcomes and for reducing racial health disparities.

Background: Scientific discovery progresses by exploring new and uncharted territory. More specifically, it advances by a process of transforming unknown unknowns first into known unknowns, and then into knowns. Over the last few decades, researchers have developed many knowledge bases to capture and connect the knowns, which has enabled topic exploration and contextualization of experimental results. But recognizing the unknowns is also critical for finding the most pertinent questions and their answers. Prior work on known unknowns has sought to understand them, annotate them, and automate their identification. However, no knowledge-bases yet exist to capture these unknowns, and little work has focused on how scientists might use them to trace a given topic or experimental result in search of open questions and new avenues for exploration. We show here that a knowledge base of unknowns can be connected to ontologically grounded biomedical knowledge to accelerate research in the field of prenatal nutrition., Results: We present the first ignorance-base, a knowledge-base created by combining classifiers to recognize ignorance statements (statements of missing or incomplete knowledge that imply a goal for knowledge) and biomedical concepts over the prenatal nutrition literature. This knowledge-base places biomedical concepts mentioned in the literature in context with the ignorance statements authors have made about them. Using our system, researchers interested in the topic of vitamin D and prenatal health were able to uncover three new avenues for exploration (immune system, respiratory system, and brain development) by searching for concepts enriched in ignorance statements. These were buried among the many standard enriched concepts. Additionally, we used the ignorance-base to enrich concepts connected to a gene list associated with vitamin D and spontaneous preterm birth and found an emerging topic of study (brain development) in an implied field (neuroscience). The researchers could look to the field of neuroscience for potential answers to the ignorance statements., Conclusion: Our goal is to help students, researchers, funders, and publishers better understand the state of our collective scientific ignorance (known unknowns) in order to help accelerate research through the continued illumination of and focus on the known unknowns and their respective goals for scientific knowledge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of this meta-analysis was to examine the associations among infant feeding types, sleeping habits, and maternal sleep postpartum. Databases including Cumulative Index of Nursing and Allied-Health Literature (CINAHL), PubMed, and Google Scholar were searched in addition to reference lists from selected articles and other key references. A critical review of relevant articles from the data sources was conducted with attention to the infant feeding types and maternal night-time sleep. The methodological quality was assessed systematically. The pooled mean difference was calculated. Narrative summaries were also used. A total of 6,472 participants from seven studies were included in the meta-analysis. A random-effects model demonstrated a significantly higher maternal night-time sleep in breastfeeding mothers than non-breastfeeding mothers with a pooled standardized mean difference of 0.24 h (95% confidence interval 0.03-0.46, p = 0.026). Co-sleeping with infants during the night also increased the sleeping hours in breastfeeding mothers. Homogeneity was observed with a Tau 2 of 0.0308 and I 2 of 44.3%. Funnel plots, Egger's and Begg's tests revealed no evidence of publication bias. This systematic review and meta-analysis demonstrated that breastfeeding may be associated with a longer night-time sleep postpartum and the synthesis of the literature suggested that co-sleeping with the infant was associated with longer sleep duration in breastfeeding women. Further research into factors involving maternal decisions on infant feeding types and their effects on maternal sleep is needed to better understand the mothers' attitude toward infant feeding and their own sleep., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Evidence-based dietary reference intakes for nutrients in healthy individuals were last set in 2005 by the Institute of Medicine. For the first time, these recommendations included a guideline for carbohydrate intake during pregnancy. The recommended dietary allowance (RDA) was set at ≥175 g/d or 45%-65% of total energy intake. In the decades since, carbohydrate intake has been declining in some populations, and many pregnant women consume carbohydrates below the RDA. The RDA was developed to account for both maternal brain and fetal brain glucose requirements. However, the placenta also requires glucose as its dominant energy substrate and is as dependent on maternal glucose as the brain. Prompted by the availability of evidence demonstrating the rate and quantity of human placental glucose consumption, we calculated a potential new estimated average requirement (EAR) for carbohydrate intake to account for placental glucose consumption. Further, by narrative review, we have re-examined the original RDA by applying contemporary measurements of adult brain and whole-body fetal glucose consumption. We also propose, using physiologic rationale, that placental glucose consumption be included in pregnancy nutrition considerations. Calculated from human in vivo placental glucose consumption data, we suggest that 36 g/d represents an EAR for adequate glucose to support placental metabolism without supplementation by other fuels. A potential new EAR of 171 g/d accounts for maternal (100 g) and fetal (35 g) brain, and now placental glucose utilization (36 g), and with extrapolation to meet the needs of nearly all healthy pregnant women, would result in a modified RDA of 220 g/d. Lower and upper safety thresholds for carbohydrate intake remain to be determined, of importance as preexisting and gestational diabetes continue to rise globally, and nutrition therapy remains the cornerstone of treatment., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe existing guidance for qualifications of principal investigator s (PI s) of human subjects research and explore how they are operationalized for pediatric nurse scientists and clinical nurses in children's hospitals., Design and Methods: After reviewing federal regulations, accreditation guidelines, and the literature, a convenience sample of members of the National Pediatric Nurse Scientist Collaborative (NPNSC). Participants completed a 33-item survey that included questions about Institutional Review Board (IRB), guidelines, and policies for PI status at their affiliated children's hospitals., Results: The survey was electronically disseminated to 179 members of NPNSC through the Collaborative's listserv. Of the 39 members who responded, 90% hold a PhD and 80% practice in a free-standing children's hospital, nearly all of which (93%) are recognized as Magnet® hospitals. While the majority of respondents indicated that nurse scientists and other nurses were allowed to be PIs of research studies, educational requirements for PI status varied, with 3% requiring a PhD, 15% a baccalaureate degree, and 10% a graduate degree. 54% of respondents reported there was no degree requirement for PI status; however15% reported that even doctorally prepared nurse scientists cannot serve as PIs of research studies at their affiliated children''s hospitals., Conclusions: The survey identified substantial variability in requirements for PI status and potential barriers to pediatric nurses conducting independent research as PIs at children's hospitals., Practice Implications: Operationalizing existing guidance will expand inclusion of nurse scientist expertise in human subjects research., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Human milk (HM) insulin plays many roles for the infant, especially for the newborn. We hypothesized HM insulin in women with type 2 diabetes (T2DM) would be higher than BMI-matched women with either gestational diabetes (GDM) or normal glucose tolerance (NGT). In T2DM, we also assessed macronutrient composition and relationships between maternal glycemic control and HM insulin., Study Design: HM was characterized at 2-weeks postpartum among three BMI-matched groups: T2DM ( n = 12), diet-controlled GDM ( n = 12), and NGT ( n = 12). In T2DM, additional fasting and postprandial HM samples were collected while wearing a continuous glucose monitor (CGM), as well as fasting and 90-minute postprandial samples after a standardized meal at 1-2 weeks postpartum., Results: Fasting HM insulin was two times higher in T2DM compared to GDM and NGT ( p < .001), which were not different from each other. Among T2DM, fasting ( p < .001) and postprandial ( p = .01) HM insulin levels were between 2 and 5× higher than plasma. Postprandial HM insulin ( p = .03) and glucose ( p < .001) were increased compared to fasting. Mean nocturnal glucose ( p < .01) and maternal hemoglobin A1c ( p < .01) positively associated with fasting HM insulin., Conclusions: These data are the first to show HM insulin concentrations are doubled in T2DM compared to BMI-matched GDM and NGT. In HM of T2DM, insulin increases postprandially, may be concentrated relative to plasma, and is influenced by maternal glycemic control, with potential clinical implications that merit further study.

Aims: To understand morning biopsychosocial factors that predict glycemia, adherence, and goal attainment in adolescents and young adults (AYA) with type 1 diabetes (T1D) on a daily basis., Methods: Eight-eight AYA (mean 17.6 ± 2.6 years, 54% female, HbA1c 7.9 ± 1.4%, diabetes duration 8.5 ± 4.5 years) with T1D who use Continuous Glucose Monitoring (CGM) completed a 2-week prospective study. Participants chose a self-management goal to focus on during participation. For six days, participants prospectively completed a 25-item Engagement Prediction Survey to assess biopsychosocial factors to predict daily diabetes outcomes and an end-of-day Goal Survey. Lasso and mixed-model regression were used to determine items in the Engagement Prediction Survey most predictive of perceived goal attainment, CGM Time-in-Range (TIR, 70-180 mg/dl), sensor mean glucose, number of insulin boluses and hyperglycemia response (bolus within 30 min of high alert or glucose <200 mg/dl within 2 hours)., Results: A 7-item model (including current glucose, planning/wanting to manage diabetes, wanting to skip self-management, feeling good about self, health perception and support needs) explained 16.7% of the daily variance in TIR, 18.6% of mean sensor glucose, 2.1% of the number of boluses, 14% of hyperglycemia response, and 28.7% of goal attainment perceptions. The mean absolute change in day-to-day TIR was 16%, sensor glucose was 30 mg/dl, and the number of boluses was 2. AYA reported more positive Engagement Prediction Survey responses on mornings when they awoke with lower glucose levels., Conclusions: Morning biopsychosocial state factors predict glycemic and adherence outcomes in AYA with diabetes and could be a novel intervention target for future behavioural interventions., (© 2022 Diabetes UK.)

Maternal-fetal consequences of exposure to blue-wavelength light are poorly understood. This study tested the hypothesis that evening blue-light exposure is associated with maternal fasting glucose and infant birthweight. Forty-one pregnant women (body mass index = 32.90 ± 6.35 kg/m 2 ; 24-39 years old; 16 with gestational diabetes mellitus [GDM]) wore actigraphs for 7 days, underwent polysomnography, and completed study questionnaires during gestational week 30 ± 3.76. Infant birthweight (n = 41) and maternal fasting glucose (n = 30; range = 16-36 weeks) were recorded from the mothers' medical charts. Blue-light exposure was obtained from Actiwatch-Spectrum recordings. Adjusted and unadjusted linear regression analyses were performed to determine sleep characteristics associated with maternal fasting glucose and infant-birthweight. The mean fasting mid- to late-gestation glucose was 95.73 ± 24.68 mg/dl and infant birthweight was 3271 ± 436 g. In unadjusted analysis, maternal fasting glucose was associated with blue-light exposure (β = 3.82, p = 0.03). In the final model of multiple linear regression for fasting glucose, evening blue-light exposure (β = 4.00, p = 0.01) remained significant after controlling for gestational weight gain, parity, sleep duration, and GDM. Similarly, blue-light exposure was associated with infant birthweight (69.79, p = 0.006) in the unadjusted model, and remained significant (β = 70.38, p = 0.01) after adjusting for weight gain, wakefulness after sleep onset, gestational age at delivery, and GDM. Higher blue-light exposure in pregnancy is associated with higher fasting glucose and infant birthweight. Reduced use of electronic devices before bedtime is a modifiable behavior., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Gestational diabetes mellitus (GDM) is associated with considerable imbalances in intestinal microbiota that may underlie pathological conditions in both mothers and infants. To more definitively identify these alterations, we evaluated the maternal and infant gut microbiota through the shotgun metagenomic analysis of a subset of stool specimens collected from a randomized, controlled trial in diet-controlled women with GDM. The women were fed either a CHOICE diet (60% complex carbohydrate/25% fat/15% protein, n=18) or a conventional diet (CONV, 40% complex carbohydrate/45% fat/15% protein, n=16) from 30 weeks' gestation through delivery. In contrast to other published studies, we designed the study to minimize the influence of other dietary sources by providing all meals, which were eucaloric and similar in fiber content. At 30 and 37 weeks' gestation, we collected maternal stool samples; performed the fasting measurements of glucose, glycerol, insulin, free fatty acids, and triglycerides; and administered an oral glucose tolerance test (OGTT) to measure glucose clearance and insulin response. Infant stool samples were collected at 2 weeks, 2 months, and 4-5 months of age. Maternal glucose was controlled to conventional targets in both diets, with no differences in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). No differences in maternal alpha or beta diversity between the two diets from baseline to 37 weeks' gestation were observed. However, women on CHOICE diet had higher levels of Bifidobacteriaceae , specifically Bifidobacterium adolescentis , compared with women on CONV. Species-level taxa varied significantly with fasting glycerol, fasting glucose, and glucose AUC after the OGTT challenge. Maternal diet significantly impacted the patterns of infant colonization over the first 4 months of life, with CHOICE infants showing increased microbiome alpha diversity (richness), greater Clostridiaceae , and decreased Enterococcaceae over time. Overall, these results suggest that an isocaloric GDM diet containing greater complex carbohydrates with reduced fat leads to an ostensibly beneficial effect on the maternal microbiome, improved infant gut microbiome diversity, and reduced opportunistic pathogens capable of playing a role in obesity and immune system development. These results highlight the critical role a maternal diet has in shaping the maternal and infant microbiome in women with GDM., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Sugino, Hernandez, Barbour, Kofonow, Frank and Friedman.)

Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be "eat better, not more." This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report "prudent" or "health-conscious" eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Youth with type 1 diabetes (T1D) often use Continuous Glucose Monitoring (CGM) devices; however, many do not wear them consistently enough to obtain optimal glycemic benefit. This study aimed to identify demographic and psychosocial predictors of optimal CGM use in adolescents with T1D to inform nurse-led interventions to improve adherence., Design and Methods: Cross-sectional survey data from youth (12-19 years) using CGM were analyzed to determine whether perceived benefits/burdens of CGM, self-efficacy, and coping predicted being a "CGM Optimizer" (wearing CGM 6-7 days/week) or "CGM Sub-user.", Results: Of 282 adolescents (54% female), 161 were CGM Optimizers and 121 were CGM Sub-Users. Optimizers were younger (15.91 ± 2.17 years vs. 16.79 ± 2.17, p = 0.001), more likely non-Hispanic White (91.9% vs 83.5%, p = 0.029), and more likely to have private insurance (82.0% vs. 69.4%, p = 0.009). Every 1-point increase on Benefits of CGM scale was associated with 2.8 times greater odds of being an Optimizer (OR = 2.82, 95% CI 1.548-5.132, p = 0.001), and every 1-point increase on the Burdens of CGM scale was associated with a 52% decrease in odds (OR = 0.48, 95% CI = 0.283-0.800, p = 0.005), with final logistic regression model (including only these two predictors) explaining 22.3% of variance., Conclusion: CGM Optimizing adolescents were more likely to perceive higher benefit and lower burden of CGM., Practical Implications: Nurse-led interventions to promote benefits of CGM and mitigate burden may help youth increase adherence with CGM to achieve glycemic benefit., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infancy associated with high morbidity and mortality. Although most prevalent following extremely preterm birth, BPD is diagnosed at 36 weeks post-menstrual age, when the disease trajectory is underway, and long-term physiological implications may be irreversible. There is an urgent and unmet need to identify how early exposures can be modified to decrease the risk of developing BPD before disease progression becomes irreversible. Extremely preterm newborns encounter a paradox at birth: oxygen is a life-sustaining component of ex utero life yet is undeniably toxic. Attempts at minimizing supplemental oxygen exposure by targeting lower oxygen saturations appear to decrease BPD but may increase mortality. Given the potential association between lower oxygen saturations and increased mortality, practice guidelines favor targeting higher saturations. This uniformly increases oxygen exposure, prompting a cascade of pathogenic mechanisms implicated in BPD development. In this review, we introduce the concept of pulmonary resilience: a homeostatic process driven by the autonomic nervous system (ANS) as a moderator of physiologic stress that when functional, could inform successful environmental adaptation following extremely preterm birth. We hypothesize that infants with early-life ANS dysfunction require a higher oxygen dose for survival; conversely, oxygen exposure could be safely limited in infants with more robust early-life ANS function, an indicator of pulmonary resilience. Characterizing the pulmonary resilience continuum to guide individualized supplemental oxygen dosing may reduce morbidity and mortality in this growing population of extremely preterm infants at risk for BPD., (© 2022 S. Karger AG, Basel.)

The original nutrition approach for the treatment of gestational diabetes mellitus (GDM) was to reduce total carbohydrate intake to 33-40% of total energy (EI) to decrease fetal overgrowth. Conversely, accumulating evidence suggests that higher carbohydrate intakes (60-70% EI, higher quality carbohydrates with low glycemic index/low added sugars) can control maternal glycemia. The Institute of Medicine (IOM) recommends ≥175 g/d of carbohydrate intake during pregnancy; however, many women are consuming lower carbohydrate (LC) diets (<175 g/d of carbohydrate or <40% of EI) within pregnancy and the periconceptual period aiming to improve glycemic control and pregnancy outcomes. This report systematically evaluates recent data (2018-2020) to identify the LC threshold in pregnancy in relation to safety considerations. Evidence from 11 reports suggests an optimal carbohydrate range of 47-70% EI supports normal fetal growth; higher than the conventionally recognized LC threshold. However, inadequate total maternal EI, which independently slows fetal growth was a frequent confounder across studies. Effects of a carbohydrate intake <175 g/d on maternal ketonemia and plasma triglyceride/free fatty acid concentrations remain unclear. A recent randomized controlled trial (RCT) suggests a higher risk for micronutrient deficiency with carbohydrate intake ≤165 g/d in GDM. Well-controlled prospective RCTs comparing LC (<165 g/d) and higher carbohydrate energy-balanced diets in pregnant women are clearly overdue.

Sleep-disordered breathing (SDB) worsens over pregnancy, and obstructive sleep apnea is associated with serious maternal complications. Intrauterine exposures that provoke insulin resistance (IR), inflammation, or oxidative stress may have long-term offspring health consequences. In obesity, worsening maternal SDB appears to be an exposure that increases the risk for both small- or large-for-gestational-age (SGA, LGA, respectively), suggesting distinct outcomes linked to a common maternal phenotype. The aim of this paper is to systematically review and link data from both mechanistic rodent models and descriptive human studies to characterize the impact of maternal SDB on fetal development. A systematic review of the literature was conducted using PubMed, Embase, and CINAHL (01/2000-09/2019). Data from rodent (9 studies) and human models (48 studies, 5 meta-analyses) were included and reviewed using PRISMA guidelines. Evidence from rodent models suggests that intermittent maternal hypoxia results in mixed changes in birth weight (BW) followed by accelerated postnatal growth, while maternal sleep fragmentation results in normal BW followed by later metabolic derangement. Human studies support that maternal SDB is associated with both SGA and LGA, both of which may predispose offspring to later obesity. Evidence also suggests a link between SDB, inflammation, and oxidative stress that may impact maternal metabolism and/or placental function. SDB is common in pregnancy and affects fetal growth and development. Given that SDB has significant potential to adversely influence the intrauterine metabolic environment, larger, prospective studies in humans are urgently needed to fully elucidate the effects of this exposure on offspring metabolic risk.

Cells in human milk are an untapped source, as potential "liquid breast biopsies", of material for investigating lactation physiology in a non-invasive manner. We used single cell RNA sequencing (scRNA-seq) to identify milk-derived mammary epithelial cells (MECs) and their transcriptional signatures in women with diet-controlled gestational diabetes (GDM) with normal lactation. Methodology is described for coordinating milk collections with single cell capture and library preparation via cryopreservation, in addition to scRNA-seq data processing and analyses of MEC transcriptional signatures. We comprehensively characterized 3740 cells from milk samples from two mothers at two weeks postpartum. Most cells (>90%) were luminal MECs (luMECs) expressing lactalbumin alpha and casein beta and positive for keratin 8 and keratin 18. Few cells were keratin 14 + basal MECs and a small immune cell population was present (<10%). Analysis of differential gene expression among clusters identified six potentially distinct luMEC subpopulation signatures, suggesting the potential for subtle functional differences among luMECs, and included one cluster that was positive for both progenitor markers and mature milk transcripts. No expression of pluripotency markers POU class 5 homeobox 1 (POU5F1, encoding OCT4) SRY-box transcription factor 2 (SOX2) or nanog homeobox (NANOG), was observed. These observations were supported by flow cytometric analysis of MECs from mature milk samples from three women with diet-controlled GDM (2-8 mo postpartum), indicating a negligible basal/stem cell population (epithelial cell adhesion molecule (EPCAM) - /integrin subunit alpha 6 (CD49f) + , 0.07%) and a small progenitor population (EPCAM + /CD49f + , 1.1%). We provide a computational framework for others and future studies, as well as report the first milk-derived cells to be analyzed by scRNA-seq. We discuss the clinical potential and current limitations of using milk-derived cells as material for characterizing human mammary physiology.

Gestational diabetes mellitus (GDM) is a worldwide public health problem affecting up to 27% of pregnancies with high predictive values for childhood obesity and inflammatory diseases. Compromised seeding of the infant gut microbiota is a risk factor for immunologic and metabolic diseases in the offspring; however, how GDM along with maternal obesity interact to alter colonization remains unknown. We hypothesized that GDM individually and in combination with maternal overweight/obesity would alter gut microbial composition, diversity, and short-chain fatty acid (SCFA) levels in neonates. We investigated 46 full-term neonates born to normal-weight or overweight/obese mothers with and without GDM, accounting for confounders including cesarean delivery, lack of breastfeeding, and exposure to antibiotics. Gut microbiota in 2-week-old neonates born to mothers with GDM exhibited differences in abundance of 26 microbial taxa; 14 of which showed persistent differential abundance after adjusting for pre-pregnancy BMI. Key pioneering gut taxa, including potentially important taxa for establishing neonatal immunity, were reduced. Lactobacillus , Flavonifractor , Erysipelotrichaceae , and unspecified families in Gammaproteobacteria were significantly reduced in neonates from mothers with GDM. GDM was associated with an increase in microbes involved in suppressing early immune cell function ( Phascolarctobacterium ). No differences in infant stool SCFA levels by maternal phenotype were noted; however, significant correlations were found between microbial abundances and SCFA levels in neonates. Our results suggest that GDM alone and together with maternal overweight/obesity uniquely influences seeding of specific infant microbiota in patterns that set the stage for future risk of inflammatory and metabolic disease., Competing Interests: JF is a consultant to the scientific advisory board of Janssen Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Soderborg, Carpenter, Janssen, Weir, Robertson, Ir, Young, Krebs, Hernandez, Barbour, Frank, Kroehl and Friedman.)

Introduction: Labor dystocia is the most common cause of cesarean birth in the United States, yet how dystocia develops during labor remains elusive. Uterine activity monitoring has significant potential for advancing our understanding of labor dystocia. While evaluating contraction frequency and amplitude is a common component of labor dystocia management, the literature describing the relationship between measures of uterine activity and labor dystocia is heterogeneous and has not been synthesized to identify the best methods for use in clinical investigation., Methods: We conducted a literature search for original research exploring the relationship between uterine activity and labor dystocia published between 2000 and 2019. Included articles were critically reviewed and synthesized., Results: Across 11 identified studies, investigators employed 3 different techniques for monitoring uterine activity and 9 different measures were employed. Uterine activity measures, including Montevideo units, uterine electromyography power density spectrum and sample entropy, and the fall-to-rise ratio of contraction shape, detected patterns associated with labor dystocia or cesarean birth., Discussion: The use of multiple regression with clinical covariates and a uterine activity measure increased the accuracy of predicting cesarean delivery. Uterine electromyography may be especially useful to evaluate labor dystocia phenotypes to differentiate uterine muscle fatigue from understimulation and lead to algorithms for increased precision in the diagnosis of labor dystocia and innovative approaches to treatment., (© 2020 The Authors. Journal of Midwifery & Women's Health published by Wiley Periodicals, Inc. on behalf of American College of Nurse Midwives (ACNM).)

Nutrition therapy provides the foundation for treatment of gestational diabetes (GDM), and has historically been based on restricting carbohydrate (CHO) intake. In this paper, randomized controlled trials (RCTs) are reviewed to assess the effects of both low- and higher CHO nutrition approaches in GDM. The prevailing pattern across the evidence underscores that although CHO restriction improves glycemia at least in the short-term, similar outcomes could be achievable using less restrictive approaches that may not exacerbate IR. The quality of existing studies is limited, in part due to dietary non-adherence and confounding effects of treatment with insulin or oral medication. Recent evidence suggests that modified nutritional manipulation in GDM from usual intake, including but not limited to CHO restriction, improves maternal glucose and lowers infant birthweight. This creates a platform for future studies to further clarify the impact of multiple nutritional patterns in GDM on both maternal and infant outcomes.

Objective: Often unrecognized, obstructive sleep apnea (OSA) worsens over pregnancy and is associated with poorer perinatal outcomes. The association between OSA in late pregnancy and metabolic biomarkers remains poorly understood. We tested the hypothesis that OSA in pregnant women with obesity is positively correlated with 24-hour patterns of glycemia and IR despite controlling for diet., Design: Pregnant women (32 to 34 weeks' gestation; body mass index, 30 to 40 kg/m2) wore a continuous glucose monitor for 3 days. OSA was measured in-home by WatchPAT 200™ [apnea hypopnea index (AHI), oxygen desaturation index (ODI; number per hour)]. Fasting blood was collected followed by a 2-hour, 75-g, oral glucose tolerance test to measure IR. Association between AHI and 24-hour glucose area under the curve (AUC) was the powered outcome., Results: Of 18 women (29.4 ± 1.4 years of age [mean ± SEM]), 12 (67%) had an AHI ≥5 (mild OSA). AHI and ODI were correlated with 24-hour glucose AUC (r = 0.50 to 0.54; P ≤ 0.03) and mean 24-hour glucose (r = 0.55 to 0.59; P ≤ 0.02). AHI and ODI were correlated with estimated hepatic IR (r = 0.59 to 0.74; P < 0.01), fasting free fatty acids (fFFAs; r = 0.53 to 0.56; P < 0.05), and waking cortisol (r = 0.49 to 0.64; P < 0.05)., Conclusions: Mild OSA is common in pregnant women with obesity and correlated with increased glycemic profiles, fFFAs, and estimates of hepatic IR. OSA is a potentially treatable target to optimize maternal glycemia and metabolism, fetal fuel supply, and pregnancy outcomes., (Copyright © 2019 Endocrine Society.)

The postpartum period represents a critical window to initiate targeted interventions to improve cardiometabolic health following pregnancies complicated by gestational diabetes mellitus and/or a hypertensive disorder of pregnancy. The purpose of this systematic review was to examine studies published since 2011 that report rates of postpartum follow-up and risk screening for women who had gestational diabetes and/or a hypertensive disorder of pregnancy and to identify disparities in care. Nine observational studies in which postpartum follow-up visits and/or screening rates were measured among US women following pregnancies complicated by gestational diabetes and/or a hypertensive disorder of pregnancy were reviewed. Rates of postpartum follow-up ranged from 5.7% to 95.4% with disparities linked to black race and Hispanic ethnicity, low level of education, and coexisting morbidities such as mental health disorders. Follow-up rates were increased if the provider was an obstetrician/endocrinologist versus primary care. Payer source was not associated with follow-up rates. The screening rate for diabetes in women who had gestational diabetes did not exceed 58% by 4 months across the studies analyzed, suggesting little improvement in the last 10 years. While women who had a hypertensive disorder appear to have had a postpartum blood pressure measured, it is unclear whether follow-up intervention occurred. Overall, postpartum screening rates for at-risk women remain suboptimal and vary substantially. Further research is warranted including reliable population-level data to inform equitable progress to meeting the evidence-informed guidelines.

With the global rising prevalence of gestational diabetes (GDM), an adaptable, economical approach to nutrition therapy that effectively controls maternal glycemia while promoting normal fetal growth will have far-reaching implications. The conventional focus has been to rigidly limit all types of carbohydrate. While controlling glucose, this approach fosters maternal anxiety and is a primary barrier to adherence. Many mothers substitute fat for carbohydrate, which may unintentionally enhance lipolysis, promote elevated free fatty acids (FFA), and worsen maternal insulin resistance (IR). Nutrition that worsens IR may facilitate nutrient shunting across the placenta, promoting excess fetal fat accretion. Evidence suggests that liberalizing higher quality, nutrient-dense carbohydrates results in controlled fasting/postprandial glucose, lower FFA, improved insulin action, vascular benefits, and may reduce excess infant adiposity. Thus, a less carbohydrate-restricted approach may improve maternal adherence when combined with higher quality carbohydrates, lower fat, appropriate caloric intake, and ethnically acceptable foods. Such a diet can be culturally sensitive, socioeconomically attentive, minimize further weight gain in GDM, with potential relevance for pregnancies complicated by overweight/obesity. Future research is needed to better understand the effect of macronutrient composition on the placenta and gut microbiome, the benefits/risks of nonnutritive sweeteners, and whether precision-nutrition is beneficial in pregnancy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Maternal obesity is associated with increased risk for offspring obesity and non-alcoholic fatty liver disease (NAFLD), but the causal drivers of this association are unclear. Early colonization of the infant gut by microbes plays a critical role in establishing immunity and metabolic function. Here, we compare germ-free mice colonized with stool microbes (MB) from 2-week-old infants born to obese (Inf-ObMB) or normal-weight (Inf-NWMB) mothers. Inf-ObMB-colonized mice demonstrate increased hepatic gene expression for endoplasmic reticulum stress and innate immunity together with histological signs of periportal inflammation, a histological pattern more commonly reported in pediatric cases of NAFLD. Inf-ObMB mice show increased intestinal permeability, reduced macrophage phagocytosis, and dampened cytokine production suggestive of impaired macrophage function. Furthermore, exposure to a Western-style diet in Inf-ObMB mice promotes excess weight gain and accelerates NAFLD. Overall, these results provide functional evidence supporting a causative role of maternal obesity-associated infant dysbiosis in childhood obesity and NAFLD.

There is increasing recognition that maternal glucose concentrations lower than those previously used for diagnosis of gestational diabetes mellitus (GDM) and targeted for treatment can result in excess fetal growth. Yet, mothers with GDM who appear to have optimal glycemic control and mothers with obesity and normal glucose tolerance still have a significantly increased risk for delivering infants who are large for gestational age, or even more importantly, who have increased adiposity at birth. What is less appreciated is that in addition to glucose, maternal lipids are also substrates for fetal fat accretion and that placental lipases can hydrolyze maternal triglycerides (TGs) to free fatty acids for fetal-placental availability. Maternal TG levels are 40% to 50% higher on average in mothers with obesity and GDM compared to those in normal-weight mothers early in pregnancy and are sustained at higher levels throughout gestation. Increasing evidence supports that maternal TG, both fasting and postprandial, are also predictors of newborn adiposity (newborn %fat), a risk factor for childhood obesity, and that early exposure is at least as strong of a risk factor as later exposure in mothers with obesity. In the setting of maternal nutrient excess and maternal insulin resistance, which lead to fetal hyperinsulinemia, excess free fatty acid exposure in the fetus may result in lipid storage and fetal fat development in subcutaneous and possibly other depots. In this commentary, we provide further evidence to make a case for targeting maternal fasting and postprandial TG in mothers with obesity who have elevated TG in early pregnancy to determine whether a TG-lowering interventional approach might limit fetal overgrowth and potentially mitigate the intrauterine contribution to childhood obesity and metabolic disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To model breastfed infant growth and body composition patterns over the first 4 months with multiple bioactive components of human milk (HM) and clinical factors (including maternal BMI status), which are related to growth., Methods: Longitudinal observation of infant growth and body composition from 0 to 4 months among 41 predominantly breastfed infants (25 mothers of Normal-weight and 16 mothers with overweight/obesity). Fasted morning HM samples were collected at 5 time-points. Macronutrients, leptin, adiponectin, ghrelin, insulin, cytokines and n-6:n-3 esterified fatty acid ratio were measured. Infant weight-for-length Z-score (WLZ) trajectory, fat-free mass (FFM) gain, fat mass gain and %fat gain were modelled controlling for clinical covariates., Results: HM insulin negatively associated with WLZ trajectory among infants of NW mothers (P = 0.028), but not associated with WLZ trajectory among infants of OW/Ob mothers. HM glucose (P < 0.001) was associated with slower rates of infant FFM gain. Infants of mothers with OW/Ob exhibited slower rates of FFM gain. HM protein, adiponectin and insulin concentrations, and n-6:n-3 ratio were all significant predictors in the model of infant fat mass gain (P < 0.03). Any amount of formula supplementation was associated with faster fat gain (P = 0.002). The model of %fat gain was similar to that of fat mass gain, excepting HM adiponectin was not a significant covariate, and a trend for maternal OW/Ob to correlate with faster %fat gain (P = 0.056)., Conclusions: Bioactive components in HM may contribute to regulation of partitioning of body composition, and these contributions may differ between mothers of normal-weight vs. with OW/Ob., (© 2018 World Obesity Federation.)

Elevated branched chain amino acids (BCAAs: valine, leucine, and isoleucine) are well-established biomarkers of obesity-associated insulin resistance (IR). Mounting evidence suggests that low- and middle-income countries are suffering from a "double burden" of both undernutrition (growth stunting) and overnutrition (obesity) as these countries undergo a "nutrition transition". The purpose of this study was to examine if pre-pregnancy body mass index (BMI, kg/m²) and a daily lipid-based micronutrient supplement (LNS, Nutriset) would lead to cross-sectional differences in circulating levels of branched chain amino acids (BCAAs) in Guatemalan women experiencing short stature during early pregnancy. Using data from an ongoing randomized controlled trial, Women First, we studied women who were normal weight (NW, BMI range for this cohort = 20.1⁻24.1 kg/m²) or overweight/obese (OW/OB, BMI range for this cohort = 25.6⁻31.9 kg/m²), and divided into two groups: those who received daily LNS ≥ 3 months prior to conception through 12 weeks gestation (+LNS), or no LNS (-LNS) ( n = 9⁻10/group). BCAAs levels were obtained from dried blood spot card samples (DBS) assessed at 12 weeks gestation. DBS cards provide a stable, efficient, and reliable means of collecting, transporting, and storing blood samples in low resource or field settings. Circulating maternal leptin, adiponectin, and insulin were determined by immunoassays from serum samples collected at 12 weeks gestation. We found maternal pre-pregnancy body mass index (ppBMI) was associated with higher circulating BCAAs ( r ² = 0.433, p = 0.002) and higher leptin/adiponectin ratio ( r = 0.466, p = 0.044) in -LNS mothers at 12 weeks gestation. +LNS mothers demonstrated no correlations between BCAAs or leptin/adiponectin ratio across ppBMI suggesting LNS may be effective at improving metabolic status in OW/OB mothers during early pregnancy.

Objective: Maternal obesity (OB) accounts for the majority of large-for-gestational-age infants, and newborn percent fat (NB%fat) correlates strongest with childhood OB. In addition to maternal glucose, fasting triglycerides (TGs) may contribute, but postprandial triglycerides (PPTGs) are unstudied. It was hypothesized that fasting TGs and PPTGs are higher in women with OB compared with women with normal weight (NW) throughout pregnancy, correlate more strongly with NB%fat than glucose, and may relate to dietary chylomicron TGs., Methods: Fasting TGs and PPTGs, free fatty acids, glucose, and insulin were prospectively measured 10 times over 4 hours after a controlled liquid breakfast early (14-16 weeks) and later (26-28 weeks) in pregnancy in 27 mothers with NW and 27 with OB. NB%fat was measured by dual x-ray absorptometry., Results: Fasting TGs and PPTGs were already ≥ 30% higher in mothers with OB at 14 to 16 weeks (P < 0.001) versus mothers with NW. In mothers with OB, a simple 1-hour (r = 0.71; P < 0.01) or 2-hour (r = 0.69; P < 0.01) PPTG at 14 to 16 weeks correlated strongest with NB%fat. In mothers with NW, the increase in TGs from early to later pregnancy correlated strongest with NB%fat (r = 0.57; P < 0.01). Maternal glucose did not statistically add to prediction models., Conclusions: These novel data suggest that 1- or 2-hour PPTGs might be a new target for early intervention in pregnancies with OB to prevent excess newborn adiposity and attenuate child OB risk., (© 2018 The Obesity Society.)

Background: Term nulliparous women have the greatest variation across hospitals and providers in cesarean rates and therefore present an opportunity to improve quality through optimal care. We evaluated associations between provider type and mode of birth, including examination of intrapartum management in healthy, laboring nulliparous women., Methods: Retrospective cohort study using prospectively collected perinatal data from a United States academic medical center (2005-2012). The sample included healthy nulliparous women with spontaneous labor onset and term, singleton, vertex fetus managed by either obstetricians or certified nurse-midwives. Univariate and multivariate logistic regression was used to compare labor interventions and mode of birth by provider type., Results: A total of 1339 women received care by an obstetrician (n = 749) or nurse-midwife (n = 590). The cesarean rate was 13.4% (179/1339). Adjusting for maternal and pregnancy characteristics, care by obstetricians was associated with an increased risk of unplanned cesarean birth (adjusted odds ratio [aOR] 1.48 [95% confidence interval {CI} 1.04-2.12]) compared with care by midwives. Obstetricians more frequently used oxytocin augmentation (aOR 1.41 [95% CI 1.10-1.80]), neuraxial anesthesia (aOR 1.69 [95% CI 1.29-2.23]), and operative vaginal delivery with forceps or vacuum (aOR 2.79 [95% CI 1.75-4.44]). Adverse maternal or neonatal outcomes were not different by provider type across all modes of birth, but were more frequent in women with cesarean than vaginal births., Discussion: In low-risk nulliparous laboring women, care by obstetricians compared with nurse-midwives was associated with increased risk of labor interventions and operative birth. Changes in labor management or increased use of nurse-midwives could decrease the rate of a first cesarean in low-risk laboring women., (© 2018 Wiley Periodicals, Inc.)

Purpose of Review: Excess fetal growth is increasingly recognized as a risk factor for childhood obesity, and mounting evidence supports that maternal glucose is not the only driver. This review focuses on the role of clinically applicable maternal non-glycemic contributors to excess fetal growth, particularly lipids, in addition to amino acids (AA), insulin resistance, inflammation, maternal nutrition, and gestational weight gain (GWG) in obesity and gestational diabetes mellitus (GDM)., Recent Findings: Lipids, specifically triglycerides and free fatty acids, appear to be strong contributors to excess fetal fat accretion and adiposity at birth, particularly in obese pregnancies, which account for the largest number of large-for-gestational-age infants. Maternal pre-pregnancy body mass index (BMI), GWG, insulin resistance, inflammation, and glucose, lipid, and AA concentrations have both independent and interacting effects on fetal growth, operating both early and late in pregnancy. All are sensitive to maternal nutrition. Early vs. later gestational exposure to excess maternal fuels in fasting and postprandial conditions may differentially impact fetoplacental outcomes. Compelling evidence suggests that targeting interventions early in pregnancy beyond glucose may be critical to improve fetal growth patterns.

Repeated venipunctures and fingersticks to confirm serum drug concentrations cause pain and dissatisfaction for pediatric patients and their families. In many organizations, the standard of care to obtain therapeutic serum drug concentrations by peripheral venipuncture or capillary fingerstick, even when the patient has an existing peripheral intravenous catheter (PIV) or central venous catheter (CVC). The primary objective of this study was to assess agreement between serum tobramycin/vancomycin concentrations collected from a CVC or PIV, versus venipuncture or fingerstick. Among hospitalized pediatric patients (age 3 months to 22 years), 36 paired blood samples were collected. Serum trough vancomycin and random tobramycin concentrations were compared between peripheral intravenous or CVC samples, and venipuncture or fingerstick samples within the same patient. A strict sampling protocol for obtaining the samples was followed, that included collection of the CVC/PIV sample before the venipuncture or fingerstick, less than 2 min between collections of samples from the different sites, and a strict volume-based flush and waste protocol. Concordant correlation coefficients demonstrated substantial agreement between CVC/PIV and venipuncture/fingerstick concentrations for vancomycin (n = 17) and tobramycin (n = 19) (Rc = 0.982 for both). Bland-Altman analyses demonstrated good overall between-method agreement within subjects and minimal bias. Consequently, using a lumen volume-based flush and waste protocol, children with indwelling catheters may not require additional venipunctures and/or fingersticks for confirmation of drug concentrations while hospitalized, improving the quality of care and patient satisfaction., (© 2018 Wiley Periodicals, Inc.)

Introduction: Recent data suggest that in addition to glucose, fetal growth is related to maternal triglycerides (TG). To reach the fetus, TG must be hydrolyzed to free fatty acids (FFA) and transported across the placenta, but regulation is uncertain. Placental lipoprotein lipase (pLPL) hydrolyzes TG, both dietary chylomicron TG (CM-TG) and very-low density lipoprotein TG (VLDL-TG), to FFA. This may promote fetal fat accretion by increasing the available FFA pool for placental uptake. We tested the novel hypothesis that pLPL activity, but not maternal adipose tissue LPL activity, is associated with newborn adiposity and higher maternal TG., Methods: Twenty mothers (n = 13 normal-weight; n = 7 obese) were prospectively recruited. Maternal glucose, insulin, TG (total, CM-TG, VLDL-TG), and FFA were measured at 14-16, 26-28, and 36-37 weeks, and adipose tissue LPL was measured at 26-28 weeks. At term delivery, placental villous biopsies were immediately analyzed for pLPL enzymatic activity. Newborn percent body fat (newborn %fat) was assessed by skinfolds., Results: Placental LPL activity was positively correlated with birthweight (r = 0.48;P = 0.03) and newborn %fat (r = 0.59;P = 0.006), further strengthened by correcting for gestational age at delivery (r = 0.75;P = 0.0001), but adipose tissue LPL was not. Maternal TG and BMI were not correlated with pLPL activity. Additionally, pLPL gene expression, while modestly correlated with enzymatic activity (r = 0.53;P < 0.05), was not correlated with newborn adiposity., Discussion: This is the first study to show a positive correlation between pLPL activity and newborn %fat. Placental lipase regulation and the role of pLPL in pregnancies characterized by nutrient excess and fetal overgrowth warrant further investigation., (Copyright © 2018. Published by Elsevier Ltd.)

Background/objectives: Excessive infant weight gain in the first 6-month of life is a powerful predictor of childhood obesity and related health risks. In mice, omega-6 fatty acids (FAs) serve as potent ligands driving adipogenesis during early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human milk (HM) has increased threefold over the last 30 years, but the impact of this shift on infant adipose development remains undetermined. This study investigated how maternal obesity and maternal dietary FA (as reflected in maternal red blood cells (RBCs) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n-3 ratio was associated with changes in infant adipose deposition between 2 weeks and 4 months postpartum., Subjects/methods: Forty-eight infants from normal weight (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were collected at either transitional (2 weeks) or established (4 months) lactation, along with infant body composition assessed using air-displacement plethysmography. The FA composition of HM and maternal RBC was measured quantitatively by lipid mass spectrometry., Results: In transitional and established HM, docosahexaenoic acid (DHA) was lower (P=0.008; 0.005) and the arachidonic acid (AA)/DHA+eicosapentaenoic acid (EPA) ratio was higher (P=0.05; 0.02) in the OB relative to the NW group. Maternal prepregnancy body mass index (BMI) and AA/DHA+EPA ratios in transitional and established HM were moderately correlated (P=0.018; 0.001). Total infant fat mass was increased in the upper AA/DHA+EPA tertile of established HM relative to the lower tertile (P=0.019). The amount of changes in infant fat mass and percentage of body fat were predicted by AA/EPA+DHA ratios in established HM (P=0.038; 0.010)., Conclusions: Perinatal infant exposures to a high AA/EPA+DHA ratio during the first 4 months of life, which is primarily reflective of maternal dietary FA, may significantly contribute to the way infants accumulate adipose.